Iron-dependent erythropoiesis in women with excessive menstrual blood losses and women with normal menses

In women of fertile age, iron loss consequent to excessive menstrual discharge is by far the most frequent cause of iron-deficient anemia. However, the relationship between menstrual discharge and iron loss is poorly understood. In this prospective study, total menstrual and iron losses were assayed in a large cohort of non-anemic women and women with excessive menstrual blood losses (menorrhagia) in order to provide data useful for intervention. One hundred and five Caucasian women aged 20–45 years were recruited. Blood cell count and serum ferritin (SF) levels were determined in each case before menses. Menstrual fluid losses (MFL) were determined using a standardized pads’ weight method.…

Rituximab for Immune Thrombocytopenia: A Retrospective Analysis on the Role of Prophylaxis Against Pneumocystis Jirovecii and Herpes Zoster Virus

Abstract Introduction and objective of the study Rituximab (RTX) is considered a valid second line treatment option for persistent or chronic Immune Thrombocytopenia (ITP). RTX is known to affect the immune system thus increasing the risk for viral and fungal infections. Although prophylactic treatment to prevent Pneumocystis jirovecii (PJ) and herpes viruses' infections is used in patients with haematological neoplasms receiving RTX, these evidence is lacking in ITP patients candidated to anti-CD20 therapy. We here reported the role of phrophylaxis in a cohort of patients treated with RTX for refractory/relapsed ITP. Methods Data from patients affected by ITP and treated at our Institution…

Cardio-oncology in multiple myeloma: is it time for a specific focus?

It has been known for some time that some oncologic drugs can cause heart damage. The term ‘cardiotoxicity’ just refers to the presence of a cardiac event during therapy or at least related to ther...

Palliative splenic irradiation in primary and post PV/ET myelofibrosis: outcomes and toxicity of three radiation schedules

Splenectomy and splenic irradiation (SI) are the sole treatment modalities to control drug resistant splenomegaly in patients with myelofibrosis (MF). SI has been used in poor surgical candidates but optimal total dose and fractionation are unclear. We retrospectively reviewed 14 MF patients with symptomatic splenomegaly. Patients received a median of 10 fractions in two weeks. Fraction size ranged from 0.2–1.4 Gy, and total dose varied from 2–10.8 Gy per RT course. Overall results indicate that 81.8% of radiation courses achieved a significant spleen reduction. Splenic pain relief and gastrointestinal symptoms reduction were obtained in 94% and 91% of courses, respectively. Severe cytopeni…

Acquired Hemophilia A Associated with Venous Thrombosis and Very High Inhibitor Titer: A Challenging Scenario

The Impact of Venous Thromboembolism In Critically Ill Patients: A Meta-Analysis of Major Clinical outcomes

Abstract Abstract 3327 Background: Critically ill patients are at high risk of developing venous thromboembolism (VTE) during their stay in the intensive care unit (ICU) because of premorbid medical and surgical conditions. The clinical consequences of Deep Vein Thrombosis (DVT) have the potential to be serious yet are frequently unrecognized in the Intensive Care Unit (ICU). In contrast to the extensive documentation on the short and long–term outcomes of patients with DVT evaluated in other clinical settings, little is known about the clinical course of this disease in the ICU setting. We hypothesized that both undetected and clinically evident VTE would affect the prognosis of critically…

Standardized low-molecular-weight heparin bridging regimen in outpatients on oral anticoagulants undergoing invasive procedure or surgery: an inception cohort management study.

BACKGROUND: Bridging therapy with low-molecular-weight heparin is usually recommended in patients who must stop oral anticoagulants before surgical or invasive procedures. To date, there is no universally accepted bridging regimen tailored to the patient's thromboembolic risk. This prospective inception cohort management study was designed to assess the efficacy and safety of an individualized bridging protocol applied to outpatients. METHODS AND RESULTS: Oral anticoagulants were stopped 5 days before the procedure. Low-molecular-weight heparin was started 3 to 4 days before surgery and continued for 6 days after surgery at 70 anti-factor Xa U/kg twice daily in high-thromboembolic-risk pati…

Combined Point of Care Tools Are Able to Improve Treatment Adherence and Health-Related Quality of Life in Patients with Severe Hemophilia: An Observational Prospective Study

Introduction: Ultrasound (US) assessment of joints is an evolving point of care tool for the detection of early joint arthropathy (Napolitano M, Kessler CM. Hemophilia A and B. Consultative Hemostasis and Thrombosis, Kitchens, 4th edition); population pharmacokinetic (pop-PK) studies are adopted as a useful instrument to set the prophylaxis regimen for patients with hemophilia, they may improve adherence (Nagao A.et al. Thromb Res. 2019 Jan; 173:79-84) and reduce the annual bleeding rate (ABR). Adherence to continuous intravenous administrations of factor VIII or Factor IX products is challenging, thus patients may experience breakthrough bleedings while on prophylaxis. Repeated US examinat…

Activated prothrombin complex concentrate (FEIBA® ) in acquired haemophilia A: a large multicentre Italian study - the FAIR Registry

IDEAL study: A real‐world assessment of pattern of use and clinical outcomes with recombinant coagulation factor IX albumin fusion protein (rIX‐FP) in patients with haemophilia B in Italy

Introduction: Factor IX replacement therapy is used for treatment and prophylaxis of bleeding in haemophilia B. rIX-FP is an extended half-life albumin-fusion protein, which, in clinical studies, has demonstrated prolonged dosing intervals up to 21 days for routine prophylaxis, providing therapeutic benefit.Aims: To describe dosing frequency and consumption (primary endpoint), efficacy and safety of rIX-FP treatment during routine clinical practice in Italy.Methods: Patients with moderate/severe haemophilia B on prophylaxis with rIX-FP for >= 6 months, were enrolled in this observational study from October 2017 to February 2019 and followed-up for 2 years. Descriptive analysis included p…

Long-Term Survival Data in 652 Patients with Primary Myelofibrosis or Polycythemia Vera— Trends in Recent Years.

Abstract Abstract 2910 Poster Board II-886 Background: Polycythemia vera (PV) and primary myelofibrosis (PMF) are stem cell-derived myeloproliferative neoplasms characterized clinically by increased red cell volume and bone marrow fibrosis, respectively. Phlebotomy is the cornerstone of treatment in PV whereas hydroxyurea has been the traditional drug of choice in both PV and PMF. Over the last 20 years, several new treatment approaches have been introduced and promoted (e.g. interferon-alpha, anagrelide, thalidomide, allogeneic stem cell transplantation) but their benefit in terms of survival has not been confirmed in controlled studies. Methods: Study patients were recruited form the Mayo…

Monoclonal Gammopathies and the Bone Marrow Microenvironment: From Bench to Bedside and Then Back Again

Multiple myeloma (MM) is an incurable hematologic malignancy characterized by a multistep evolutionary pathway, with an initial phase called monoclonal gammopathy of undetermined significance (MGUS), potentially evolving into the symptomatic disease, often preceded by an intermediate phase called “smoldering” MM (sMM). From a biological point of view, genomic alterations (translocations/deletions/mutations) are already present at the MGUS phase, thus rendering their role in disease evolution questionable. On the other hand, we currently know that changes in the bone marrow microenvironment (TME) could play a key role in MM evolution through a progressive shift towards a pro-inflammatory and…

The new HFA/ICOS risk assessment tool to identify patients with chronic myeloid leukaemia at high risk of cardiotoxicity

AimsTyrosine kinase inhibitors (TKIs) used to treat chronic myeloid leukaemia (CML) can cause cardiovascular adverseevents. So far, the Systematic Coronary Risk Evaluation (SCORE) charts of the European Society of Cardiology (ESC) have beenused to identify cancer patients at increased cardiovascular risk. The primary aim of our study was to evaluate the usefulnessof the new cardiovascular risk assessment model proposed by the Cardio-Oncology Study Group of the Heart Failure Associ-ation (HFA) of the ESC in collaboration with the International Cardio-Oncology Society (ICOS) to stratify the cardiovascular riskin CML patients, compared with SCORE risk charts. The secondary aim was to establish…

Calculated Whole Blood Viscosity and Albumin/Fibrinogen Ratio in Patients with a New Diagnosis of Multiple Myeloma: Relationships with Some Prognostic Predictors

Background: In this single center study, we retrospectively evaluated the calculated hemorheological profile in patients with a new diagnosis of multiple myeloma, with the aim to evaluate possible relationships with some prognostic predictors, such as ISS, albumin levels, beta2-microglobulin, red cell distribution width, and bone marrow plasma cell infiltration. Methods: In a cohort of 190 patients, we examined the calculated blood viscosity using the de Simone formula, and the albumin/fibrinogen ratio as a surrogate of erythrocyte aggregation, and then we related these parameters to prognostic factors, using the Kruskal–Wallis and the Mann–Whitney tests, respectively. Results: From our ana…

Residual vein thrombosis to establish duration of anticoagulation after a first episode of deep vein thrombosis: the Duration of Anticoagulation based on Compression UltraSonography (DACUS) study

Abstract Residual vein thrombosis (RVT) indicates a prothrombotic state and is useful for evaluating the optimal duration of oral anticoagulant treatment (OAT). Patients with a first episode of deep vein thrombosis, treated with OAT for 3 months, were managed according to RVT findings. Those with RVT were randomized to either stop or continue anticoagulants for 9 additional months, whereas in those without RVT, OAT was stopped. Outcomes were recurrent venous thromboembolism and/or major bleeding. Residual thrombosis was detected in 180 (69.8%) of 258 patients; recurrent events occurred in 27.2% of those who discontinued (25/92; 15.2% person-years) and 19.3% of those who continued OAT (17/88…

Il dosaggio biologico dei fattori della coagulazione e degli inbitori del fattore VIII

Serial 2-Point Ultrasonography Plus D-Dimer vs Whole-Leg Color-Coded Doppler Ultrasonography for Diagnosing Suspected Symptomatic Deep Vein Thrombosis

Context Patients with suspected deep vein thrombosis ( DVT) of the lower extremities are usually investigated with ultrasonography either by the proximal veins ( 2-point ultrasonography) or the entire deep vein system ( whole- leg ultrasonography). The latter approach is thought to be better based on its ability to detect isolated calf vein thrombosis; however, it requires skilled operators and is mainly available only during working hours. No randomized comparisons are yet available evaluating the relative values of these 2 strategies. Objective To assess if the 2 diagnostic strategies are equivalent for the management of symptomatic outpatients with suspected DVT of the lower extremities.…

COMPARISON OF CLINICAL AND LABORATORY DATA, INCLUDING JAK-2 46/1 HAPLOTYPE, BETWEEN PATIENTS WITH IDIOPATHIC ERYTHROCYTOSIS AND POLYCYTHEMIA VERA.

Hematopoietic Peripheral Circulating Blood Stem Cells As an Independent Marker of Good Transfusion Management in Patients with Beta-Thalassemia

Abstract Aim Aim of the current study was to prospectively evaluate the potential role of peripheral circulating CD34+ stem cells as new independent marker of appropriate hemopoietic balance in patients with thalassemia major and intermedia. Materials and methods Peripheral blood samples from patients with thalassemia major (TM) and intermedia (TI) were drawn. Peripheral circulating CD34+ stem cells, CF-GEMM, CFU-GM and BFU-GM were assayed with monoclonal antibodies for CD34 and clonogenic tests, according to standard procedures and ISHAGE method (BD stem cell enumeration kit, Becton Dickinson; H4434, Stem Cell Technology). Demographic and clinical data were recorded from each enrolled subj…

Oral Communication

Inherited factor VII (FVII) deficiency is the most common of the rare autosomal recessive bleeding disorders (RBD), with an estimated prevalence of 1 per 300,000 in European countries.1,2 It is likely that the prevalence is higher in those countries where consanguineous marriages are frequent.We here report STER study results on 112 evaluable enrolled cases

PREDICTORS OF RESIDUAL VEIN THROMBOSIS AFTER CANCER-RELATED DEEP VEIN THROMBOSIS OF THE LOWER LIMBS

Home therapy for deep vein thrombosis and pulmonary embolism in cancer patients

Outpatient treatment of deep vein thrombosis (DVT) has become a common practice in uncomplicated patients. Few data are still present in patients with comorbidity (such as cancer) or concomitant symptomatic pulmonary embolism. Cancer patients with DVT are often excluded from home treatment because they have a higher risk of both bleeding and recurrent DVT. We tested the feasibility and safety of the Home Treatment (HT) program for acute DVT a PE in cancer patients. Patients were treated as outpatients unless they required admission for other medical problems, were actively bleeding or had pain that requires parenteral narcotics. Outpatient treatment was with low molecular weight heparin (LM…

How the coronavirus pandemic has affected the clinical management of Philadelphia-negative chronic myeloproliferative neoplasms in Italy—a GIMEMA MPN WP survey

Since early 2020, the SARS-CoV-2 pandemic has a massive impact on health care systems worldwide. Patients with malignant diseases are assumed to be at increased risk for a worse outcome of SARS-CoV-2 infection, and therefore, guidance regarding prevention and management of the infection as well as safe administration of cancer-therapy is required. Here, we provide recommendations for the management of patients with malignant disease in the times of COVID-19. These recommendations were prepared by an international panel of experts and then consented by the EHA Scientific Working Group on Infection in Hematology. The primary aim is to enable clinicians to provide optimal cancer care as safely…

Health status and quality of life of elderly persons with severe hemophilia born before the advent of modern replacement therapy

SUMMARY BACKGROUND: More and more people with severe hemophilia reach an old age thanks to an effective treatment. There is no information on the health status and quality of life of elderly people with hemophilia born at a time when replacement therapy was hardly available. METHODS: Italian patients with severe hemophilia, aged >or=65 years and hence born in 1942 or earlier, were compared with elderly men without bleeding disorders matched for age, sex, geography and social status. The following aspects were evaluated: concomitant illness, orthopedic status, physical functioning and cognitive status. Measurements of generic and disease-specific health-related quality of life were also obta…

Phase III studies on novel oral anticoagulants for stroke prevention in atrial fibrillation -a look beyond the excellent results

Abdominal aortic thrombosis secondary to reactive thrombocytosis in a patient with iron deficiency anemia

Hematopoietic peripheral circulating blood stem cells as an independent marker of good transfusion management in patients with β-thalassemia: results from a preliminary study

Background Beyond hemoglobin (Hb) levels and performance status, further surrogate markers of appropriate transfusion management should improve the quality of thalassemia care. We investigated the levels of peripheral circulating CD34+ stem cells as an independent marker of appropriate hematopoietic balance in patients with thalassemia. Study design and methods Peripheral circulating CD34+ stem cells, colony-forming unitgranulocyte, erythrocyte, macrophage, magakaryocyte (CF-GEMM), colony-forming unitgranulocyte/macrophage (CFU-GM), and erythroidburst-forming units (BFU-E) were assayed, according to standard procedures. Patients with thalassemia major (TM) and thalassemia intermedia (TI) we…

Buffy coat-derived platelets cryopreserved using a new method: Results from in vitro studies

Abstract Cryopreservation for the long-term storage of platelets (PLTs) is a useful method to overcome the limits of platelet shortage. This is an in vitro prospective study to evaluate the count, viability, and function of buffy coat-derived pooled platelet concentrates (BC-PLTs), treated with dimethyl sulphoxide (DMSO) and cryopreserved (CRY BC-PLTs) at −80 °C with a modified Valeri method. PLTs were stored in 6% DMSO with a patented kit. Overall, 49 BC-PLTs from 245 healthy volunteer donors were prepared, cryopreserved, and analysed before and after 3, 6, and 9 months of storage. In flow cytometry, a statistically significant reduction in CD 42b (92.7 ± 4.29% at T0 vs. 23.6 ± 27.5% at T3…

High BCR-ABL/GUS(IS) levels at diagnosis of chronic phase CML are associated with unfavorable responses to standard-dose imatinib

Abstract Purpose: The approval of second-generation tyrosine kinase inhibitors (TKIs) for the first-line treatment of chronic myeloid leukemia (CML) has generated an unmet need for baseline molecular parameters associated with inadequate imatinib responses. Experimental Design: We correlated BCR–ABL/GUSIS and BCR–ABL/ABL transcripts at diagnosis with the outcome—defined by the 2013 European LeukemiaNet recommendations—of 272 patients newly diagnosed with CML receiving imatinib 400 mg/daily. Applying receiver-operating characteristic curves, we defined BCR–ABL/GUSIS and BCR–ABL/ABL levels associated with lower probabilities of optimal response, failure-free (FFS), event-free (EFS), transform…

THE PERSISTANCE OF RESIDUAL VEIN THROMBOSIS, AFTER AN EPISODE OF DEEP VEIN THROMBOSIS, AND THE RISK OF NEW OVERT CANCER AND CARDIOVASCULAR DISEASE

Detection and clinical implications of a novel BCR-ABL1 E12A2 insertion/deletion in a CML patient expressing the E13A2 isoform

Background/Aim: The Philadelphia chromosome is the most frequent cytogenetic abnormality in chronic myelogenous (CML). More than 95% of CML patients are diagnosed with the e13a2 or e14a2 BCR-ABL1 fusion transcripts while, in about 1% of these individuals, the break generates the e1a2 rearrangement. Furthermore, about 5% of CML patients are diagnosed with rare BCR-ABL1 fusion transcripts, such as e19a2, e8a2, e13a3, e14a3, e1a3 and e6a2. However, there is limited evidence concerning the clinical and prognostic implications of these infrequent oncogenic variants for CML patients receiving tyrosine kinase inhibitors (TKIs). Case Report: We describe a novel atypical e12a2 insertion/deletion (In…

Multiple Myeloma-Derived Extracellular Vesicles Induce Osteoclastogenesis through the Activation of the XBP1/IRE1α Axis

Bone disease severely affects the quality of life of over 70% of multiple myeloma (MM) patients, which daily experience pain, pathological fractures, mobility issues and an increased mortality. Recent data have highlighted the crucial role of the endoplasmic reticulum-associated unfolded protein response (UPR) in malignant transformation and tumor progression

Clinical Phenotype and Response to Different Lines of Therapy in Elderly with Immune Thrombocytopenia: A Retrospective Study

Salvatrice Mancuso,1 Melania Carlisi,1 Nicola Serra,2,3 Mariasanta Napolitano,1 Simona Raso,3 Ugo Consoli,4 Roberto Palazzolo,5 Maria Rosa Lanza Cariccio,6 Sergio Siragusa1 1Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE) Department, University of Palermo, Palermo, Italy; 2Department of Molecular Medicine and Medical Biotechnology, University Federico II of Naples, Naples, Italy; 3Department of Surgical, Oncological and Stomatological Disciplines, University of Palermo, Palermo, Italy; 4UOC Ematologia ARNAS Garibaldi, Catania, Italy; 5UOS Ematologia, Asst Valtellina e Alto Lario, Sondrio, Italy; 6Dipartimento Oncologico, La Maddalena,…

Laying the foundations for gene therapy in Italy for patients with haemophilia A: A Delphi consensus study

IntroductionCurrent treatment for haemophilia A involves factor VIII replacement or non-replacement (emicizumab) therapies, neither of which permanently normalise factor VIII levels. Gene therapy using adeno-associated viral (AAV) vectors is an emerging long-term treatment strategy for people with severe haemophilia A (PwSHA) that is likely to be available for clinical use in the near future. AimThis article proposes practical guidelines for the assessment, treatment, and follow-up of potential PwSHA candidates for AAV-based gene therapy. MethodUsing the Delphi method, a working group of Italian stakeholders with expertise in and knowledge of the care of adults with haemophilia A analysed l…

Residual vein thrombosis and D-dimer for optimizing duration of anticoagulation in idiopathic deep vein thrombosis.

Long-term anticoagulant treatment is highly effective in preventing recurrent Venous Thrombo-Embolism (VTE) in patients with idiopathic Deep Vein Thrombosis (DVT) of the lower limbs, though associated with an increased risk for major bleeding that may offset the benefits of anticoagulation. Accordingly to recent guidelines, patients with idiopathic DVT should be treated for at least 3 months and then should be evaluated for the risk-benefit ratio of long-term therapy. However, such ‘time for decision’ is often unclear and the optimal duration of VKA remains debatable. In recent studies, markers for the assessment of the individual risk for recurrent thrombosis have been proposed, which can …

PRACTICAL RECOMMENDATIONS FOR THE MANAGEMENT OF PATIENTS WITH ITP DURING THE COVID-19 PANDEMIC

The current COVID-19 pandemic requires revisiting our current approach to major blood disorders, including ITP (Immune Thrombocytopenia), stirring  up the production of several disease-specific practical guidelines. This report describes an updated version of consensus-based practical guidelines on the management of ITP, adapted to the Italian health system and social context.  It highlights the role of the hematologist in offering guidance for choosing differentiated approaches in relation to specific circumstances and is intended to provide them with a useful tool for sharing the decision-making process with their patients.
 Probably, the greatest risk to avoid for a patient with sus…

Cancer-Related Venous Thrombosis: Residual Vein Thrombosis Improves Screening for Occult Cancer.

Abstract Background. Clinical advantages of extensive screening for occult cancer in patients with idiopathic Deep Vein Thrombosis (DVT) is still debated since this approach improves early detection of cancer but not cancer-related mortality. Recently, we have demonstrated that patients with Residual Vein Thrombosis (RVT), 3 months after DVT, have a high risk for cancer in the subsequent 2 years (Siragusa S et al. Blood2005;106(11):OC262). At the present it is unknown whether RVT assessment may be used to select patients, with idiopathic DVT, who require screening for occult cancer. Objective of the study. We conducted a prospective study evaluating whether a RVT-based screening for cancer …

Transfusion-dependency at presentation and its acquisition in the first year of diagnosis are both equally detrimental for survival in primary myelofibrosis - prognostic relevance is independent of IPSS or karyotype

The International Prognostic Scoring System (IPSS) and karyotype are useful tools for risk stratification in primary myelofibrosis (PMF). We examined the additional prognostic impact of red blood cell transfusion need among 254 consecutive patients (median age, 59 years). Sixty-two patients ( approximately 24%) required transfusions at diagnosis whereas 22 ( approximately 9%) became transfusion-dependent and 170 remained transfusion-independent during the first year postdiagnosis; after a median follow-up of 55 months, the respective median survivals were 35, 25, and 117 months (P < 0.01). Multivariable analysis confirmed the IPSS- and karyotype-independent prognostic weight of transfusion …

Extracellular Vesicle microRNAs Contribute to the Osteogenic Inhibition of Mesenchymal Stem Cells in Multiple Myeloma

Osteolytic bone disease is the major complication associated with the progression of multiple myeloma (MM). Recently, extracellular vesicles (EVs) have emerged as mediators of MM-associated bone disease by inhibiting the osteogenic differentiation of human mesenchymal stem cells (hMSCs). Here, we investigated a correlation between the EV-mediated osteogenic inhibition and MM vesicle content, focusing on miRNAs. By the use of a MicroRNA Card, we identified a pool of miRNAs, highly expressed in EVs, from MM cell line (MM1.S EVs), expression of which was confirmed in EVs from bone marrow (BM) plasma of patients affected by smoldering myeloma (SMM) and MM. Notably,we found that miR-129-5p, whic…

Prevalence of renal failure and use of antithrombotic prophylaxis among medical inpatients at increased risk of venous thromboembolic events.

Abstract Background Evidence-based guidelines recommend the use of antithrombotic prophylaxis in medical patients at risk of venous thromboembolism (VTE). Low molecular weight heparins (LMWHs) are usually preferred to unfractionated heparin. However, when prophylactic doses of LMWH are administered, patients with renal failure (RF) are exposed to the risk of excessive accumulation, and thus to an increased risk of bleeding. We aimed to assess the prevalence of RF among medical inpatients at increased risk of VTE and the use and dosage of antithrombotic prophylaxis in these patients. Methods In a cross sectional study carried out at three different hospitals, information on all medical inpat…

Sex-related characteristics of cerebral vein thrombosis: A secondary analysis of a multicenter international cohort study.

Risk of Recurrence After a First Episode of Symptomatic Venous Thromboembolism Provoked by a Transient Risk Factor A Systematic Review

Background We aimed to determine the risk of recurrence for symptomatic venous thromboembolism (VTE) provoked by different transient risk factors. Data Sources MEDLINE, EMBASE, and Cochrane Collaboration Registry of Randomized Trials databases were searched. Study Selection Prospective cohort studies and randomized trials of patients with a first episode of symptomatic VTE provoked by a transient risk factor and treated for at least 3 months were identified. Data Extraction Number of patients and recurrent VTE during the 0- to 12-month and 0- to 24-month intervals after stopping therapy, study design, and provoking risk factor characteristics were extracted. Data Synthesis Annualized recurr…

Replacement Therapy for Surgery in FVII Deficiency: The Ster Experience Concerning 63 Interventions.

Abstract Abstract 1290 Poster Board I-312 Background Excessive bleeding represents a major complication of surgical interventions, and its control is especially relevant in patients with Congenital Bleeding Disorders. In FVII deficiency, scanty data is available in surgery to guide treatment strategies. Methods The STER (Seven Treatment Evaluation Registry) is a multi-centre, prospective, observational, web-based registry providing the frame for an extensive and structured data collection. Results As of Dec. 2008, sixty-three surgical operations (36 “major” and 27 “minor”) were performed in 54 subjects (29 females and 25 males) with a FVII deficiency (31 previously symptomatic; 9 with FVIIc…

Plasma viscosity pattern and erythrocyte aggregation in two patients with congenital afibrinogenemia

: In this case report, we examine the behavior of plasma viscosity, explored at high and low shear rates, and erythrocyte aggregation in two patients with congenital afibrinogenemia, a clinical disorder firstly described in 1920 and that has an estimated incidence of 1 : 1-200 0000. The two hemorheological parameters examined by us showed a marked decrease in both patients, in one of whom erythrocyte aggregation was even undetectable. Keeping in mind that spontaneous thrombosis (venous and arterial) has been often described in congenital afibrinogenemia, it can be hypothesized that the decrease in plasma viscosity and erythrocyte aggregation might cause a reduction of the endothelial synthe…

The Persistance of Residual Vein Thrombosis, after an Episode of Deep Vein Thrombosis, and the Risk of New Overt Cancer and Cardiovascular Disease

Background. We have recently demonstrated that the presence of Residual Vein Thrombosis (RVT), UltraSonography (US)-detected at the 3rd month after an episode of Deep Vein Thrombosis (DVT) of the lower limbs, is an independent risk factor for developing recurrent Venous Thromboembolism (VTE). The management of DVT patients by detection of RVT may, therefore, represent a simple and reproducible method for establishing the individual risk of recurrence and for tailoring the optimal duration of Oral Anticoagulants (OA) (Siragusa S et al. Blood 2003;102(11):OC183a). At the present, it is unknown whether RVT may also identify patients at increased risk for cancer and/or cardiovascular disease (C…

Ferritin Metabolism Reflects Multiple Myeloma Microenvironment and Predicts Patient Outcome

Multiple myeloma (MM) is a hematologic malignancy with a multistep evolutionary pattern, in which the pro-inflammatory and immunosuppressive microenvironment and genomic instability drive tumor evolution. MM microenvironment is rich in iron, released by pro-inflammatory cells from ferritin macromolecules, which contributes to ROS production and cellular damage. In this study, we showed that ferritin increases from indolent to active gammopathies and that patients with low serum ferritin had longer first line PFS (42.6 vs. 20.7 months and, p = 0.047, respectively) and OS (NR vs. 75.1 months and p = 0.029, respectively). Moreover, ferritin levels correlated with systemic inflammation markers …

Incidence of venous thromboembolism and use of anticoagulation in hematological malignancies: Critical review of the literature.

Venous Thromboembolism (VTE) frequently complicates the course of hematologic malignancies (HM) and its incidence is similar to that observed in high-risk solid tumors. Despite that, pharmacologic prophylaxis and treatment of VTE in patients with HM is challenging, mainly because a severe thrombocytopenia frequently complicates the course of treatments or may be present since diagnosis, thus increasing the risk of bleeding. Therefore, in this setting, safe and effective methods of VTE prophylaxis and treatment have not been well defined and hematologists generally refer to guidelines produced for cancer patients that give indications on anticoagulation in patients with thrombocytopenia. In …

Lymphomas and thyroid: Bridging the gap

The thyroid gland is often involved in the development of neoplastic diseases, including lymphoproliferative disorders. The aim of this paper is to provide a comprehensive overview of the multiple interactions between lymphoma and thyroid. Through an extensive research among the literature, the relationship between lymphomas and thyroid can be established at various levels, and the possible interconnections are here summarized in 5 points: (1) the greater risk of lymphoma development in some thyroid diseases; (2) the primary thyroid lymphoma, with focus on issues related to the diagnosis, differential diagnosis, and treatment; (3) the incidence of thyroid involvement in primitive nodal lymp…

Molecular-Biology-Driven Frontline Treatment for Chronic Lymphocytic Leukemia: A Network Meta-Analysis of Randomized Clinical Trials

The treatment of chronic lymphocytic leukemia (CLL) currently relies on the use of chemo-immunotherapy, Bruton’s tyrosine kinase inhibitors, or BCL2 inhibitors alone or combined with an anti-CD20 monoclonal antibody. However, the availability of multiple choices for the first-line setting and a lack of direct head-to-head comparisons pose a challenge for treatment selection. To overcome these limitations, we performed a systematic review and a network meta-analysis on published randomized clinical trials performed in the first-line treatment setting of CLL. For each study, we retrieved data on progression-free survival (according to del17/P53 and IGHV status), overall response rate, complet…

Thrombophilia in women with unexplained fetal loss

ABSOLUTE LYMPHOCYTE COUNT IS NOT A PREDICTOR FOR SURVIVAL IN NEWLY DIAGNOSED ELDERLY PATIENTS WITH MULTIPLE MYELOMA. FINAL RESULTS OF A MULTICENTER STUDY

Management of the Sponataneous Bleeding Episodes in Factor VII Deficiency. A Prospective Evaluation of the STER,

Abstract Abstract 3368 Introduction Patients with an inherited factor VII (FVII) deficiency may display a wide range of clinical phenotypes, from an asymptomatic condition to serious hemorrhagic episodes such as fatal central nervous system (CNS) or gastrointestinal (GI) bleeds (Mariani G et al. Thromb Haemost 2005; 93: 481–7). Symptomatic patients can be divided into two major categories: those with mild-to-moderate bleeding tendency and individuals with a severe bleeding tendency which may be more severe than that in hemophilia. The former group mainly experience mucosal bleeding, a clinical picture that mimics that of a platelet disorder and often does not call for treatment. In contrast…

Absolute lymphocyte count is unrelated to overall survival in newly diagnosed elderly patients with multiple myeloma treated with immunomodulatory drugs

The absolute lymphocyte count (ALC) has been widely studied in hematologic and solid malignancies as a marker of host antitumor immunity. Its significance has been evaluated in multiple myeloma (MM...

Cardiovascular risk factor in MPN patients

Residual vein thrombosis estabilishes the optimal duration of oral anticoagulants for the treatment od DVT

Optimal duration of antithrombotic therapy in carcer patients with deep vein thrombosis: the role of residual vein thrombosis. the cancer dacus

Gastrointestinal bleeding due to angiodysplasia in patients with type 1 von Willebrand disease: report on association and management

Management of bleeding and of invasive procedures in patients with platelet disorders and/or thrombocytopenia: Guidelines of the Italian Society for Haemostasis and Thrombosis (SISET).

The optimal management of bleeding or its prophylaxis in patients with disorders of platelet count or function is controversial. The bleeding diathesis of these patients is usually mild to moderate: therefore, transfusion of platelet concentrates may be inappropriate, as potential adverse effects might outweigh its benefit. The availability of several anti-hemorrhagic drugs further compounds this problem, mainly because the efficacy/suitability of the various treatment options in different clinical manifestations is not well defined. In these guidelines, promoted by the Italian Society for Studies on Haemostasis and Thrombosis (Società Italiana per lo Studio dell'Emostasi e della Trombosi […

Successful treatment of acquired haemophilia with FEIBA and Retuximab

Differences among young adults, adults and elderly chronic myeloid leukemia patients

Abstract BACKGROUND: The incidence of chronic myeloid leukemia (CML) increases with age, but it is unclear how the characteristics of the disease vary with age. In children, where CML is very rare, it presents with more aggressive features, including huge splenomegaly, higher cell count and higher blast cell percentage. PATIENTS AND METHODS: To investigate if after childhood the disease maintains or loses these characteristics of aggressiveness, we analyzed 2784 adult patients, at least 18 years old, registered by GIMEMA CML WP over a 40-year period. RESULTS: Young adults (YAs: 18-29 years old) significantly differed from adults (30-59 years old) and elderly patients (at least 60 years old)…

Drug-related cardiotoxicity for the treatment of haematological malignancies in elderly.

Several publications have focused on the cardiotoxicity of specific classes of haematological therapeutic agents such as antracyclines and cyclofosfamide. Cardiotoxicity of cancer chemotherapeutics is a problem for patients of all ages, but it increases with age. Toxicity can also be developed months after the last chemotherapy dose, and late reactions can be seen years later when they present new-onset cardiomyopathy. No data are available about the cardiotoxicity of non-chemotherapy agents currently used as preferred therapy for haematological malignancy in elderly. In this review we have provided a summary of the cardiovascular toxic effects produced by different drugs and therapeutic ag…

Trombosi portale mesenterica idiopatica in paziente con doppia mutazione eterozigote del gene C677T e del gene A1298C della MTHFR

CANCER AS A PREDICTOR FOR INCREASED PERIPROCEDURAL BLEEDING DURING SURGERY OR PLATELET-INDUCED CHEMOTHERAPY IN CHRONICALLY ANTICOAGULATED PATIENTS

Residual Vein Thrombosis Improves Screening for Occult Cancer: Results On 537 Patients with Idiopathic Deep Vein Thrombosis

Abstract Abstract 3999 Poster Board III-935 Background Clinical advantage of extensive screening for occult cancer in patients with idiopathic Deep Vein Thrombosis (DVT) is unknown. We have demonstrated that the Residual Vein Thrombosis (RVT)-based screening for occult cancer improves early detection as well as cancer-related mortality (Siragusa S et al. Blood 2007;110(699):OC). Here we report on final analysis of 537 patients over a period of 8 years. Objective of the study We conducted a prospective study evaluating whether a RVT-based screening for cancer is sensitive and influences cancer-related mortality. Study design Prospective with two cohorts of DVT patients: the first cohort was …

Objectives and methodology: Guidelines of the Italian Society for Haemostasis and Thrombosis (SISET).

A current goal of the Italian Society for Thrombosis and Haemostasis (SISET) is the production of guidelines for clinical conditions related to haemostasis and thrombosis. In 2006, the Executive Committee of SISET adopted a new program for the production of methodologically and scientifically sound guidelines aimed at both addressing clinical practice and stimulating new research. The first major step for this program was to train methodologists to manage working groups that compose the guidelines, and to create a reference document that describes the development of the program. The aim of the present paper is to report a short version of this methodological document, for those who wish to …

Residual vein thrombosis assessment estabilishes the optimal duration of oral anticoagulants in patients with idiopatic or provoked deep vein thrombosis. a randomized, controlled trial

Comparison between whole blood viscosity measured and calculated in subjects with monoclonal gammopathy of undetermined significance and in patients with multiple myeloma: Re-evaluation of our survey.

BACKGROUND: in this study, with a re-evaluation of the hemorheological determinants previously described in MGUS subjects and in MM patients, we have detected the calculated whole blood viscosity, according whether to the hematocrit and total plasma protein concentration (de Simone formula) or to the haematocrit and plasma fibrinogen level (Merrill formula), and a marker of the erythrocyte aggregation (albumin/fibrinogen level). METHODS: data were expressed as means±standard deviation. Student’s t test for unpaired data was used to compare MGUS subjects and MM patients. The correlation coefficient between mean erythrocyte aggregation (MEA) and hematocrit (Ht) was evaluated in MGUS, MM and M…

The Essential Thrombocythemia in 2020: What We Know and Where We Still Have to Dig Deep

The Essential Thrombocythemia is a Chronic Philadelphia-negative Myeloproliferative Neoplasm characterized by a survival curve that is only slightly worse than that of age- and sex-adjusted healthy population. The criteria for diagnosis were reviewed in 2016 by WHO. The incidence varies from 0.2 to 2.5:100 000 people per year, with a prevalence of 38 to 57 cases per 100 000 people. The main characteristics of ET are the marked thrombocytosis and the high frequency of thrombosis. The spectrum of symptoms is quite wide, but fatigue results to be the most frequent. Thrombosis is frequently observed, often occurring before or at the time of diagnosis. The classification of thrombotic risk has …

SUPERFICIAL VENOUS THROMBOSIS: ROLE OF GENETIC RISK FACTORS ON SPREADING TO DEEP VEINS

Prolonged anticoagulant treatment in patients with cancer: Where do we stand?

Test di I livello nella diagnostica della malattia di Von Willebrand" in "Emocoagulazione ed Emostasi

A commentary: To screen for calf DVT or not to screen? The highly variable practice among italian centers highlights this important and still unresolved clinical opinion. Results from the italian MASTER registry

Philadelphia chromosome-negative myeloproliferative neoplasms in younger adults: A critical discussion of unmet medical needs, with a focus on pregnancy

Abstract Myeloproliferative neoplasms (MPN) are traditionally regarded as a disease of older adults, though a not negligible fraction of cases occurs at a younger age, including women of childbearing potential. MPN in younger patients, indeed, offer several challenges for the clinical hematologist, that goes from difficulties in reaching a timely and accurate diagnosis to a peculiar thrombotic risk, with a relatively high incidence of thromboses in unusual sites (as the splanchnic veins or the cerebral ones). Moreover, the issue of pregnancy is recently gaining more attention as maternal age is rising and molecular screening are widely implemented, leading to a better recognition of these c…

Trombosi venosa superficiale ed estensione al circolo profondo: ruolo dei fattori di rischio genetici

Real-World Management of Myelofibrosis with Ruxolitinib: Initial Analysis of an Italian Observational Study (ROMEI)

Abstract Introduction ROMEI (CINC424AIT04 Ruxolitinib Observational study in Myelofibrosis treated patiEnts in Italy) is a prospective observational study that aims to bridge the knowledge gap between the clinical experience of registration trials and routine patient management by following roughly 200 myelofibrosis (MF) patients (pts) treated with ruxolitinib in everyday clinical practice. Enrollment began in April 2017 and ended in May 2018. Methods The primary endpoint is to evaluate changes in symptoms and quality of life during treatment with ruxolitinib through the Myeloproliferative Neoplasm 10 (MPN-10) disease-specific questionnaire and EuroQoL-5D-5L (EQ-5D-5L) general health questi…

ENDOGENOUS THROMBIN POTENTIAL IN PATIENTS WITH IDIOPATHIC VENOUS THROMBOSIS

Adverse Events in Treatment of Inherited Factor VII Deficiency: Final Analysis of the STER

Abstract Abstract 2279 Introduction No evidence-based guidelines are available for the treatment of Factor VII deficiency. Replacement therapy (RT) is still influenced by different factors as rarity of the disorder, availability and supply of products and economic reasons. All RTs are not exempt of side effects and scanty data is available about the safety of the products currently used. Aim of this study was to analyze adverse events (AEs) of RTs for congenital Factor VII deficiency, as reported in Seven Treatment Evaluation Registry (STER). Design and Methods FVII deficiency patients treated for bleeding episodes, prophylaxis, and surgery were investigated for RT-related AEs over a period…

Objective Assessment of Pulmonary Embolism Can Be Deferred without Increased Risk

Abstract Background. Management of patients with suspected Pulmonary Embolism (PE) is problematic if diagnostic imaging is not available. Pretest Clinical Probability (PCP) and D-dimer (D-d) assessment were shown to be useful to identify those high risk patients for whom empirical, protective anticoagulation is indicated (Siragusa S et al. Arch Intern Med2004;164:2477–82). Objective of the study. In consecutive patients with suspected PE, we evaluated whether PCP and D-d assessment, together with the use of low molecular weight heparins (LMWHs), allow objective appraisal of PE to be deferred for up to 72 hours. Methods. In case of deferment of diagnostic imaging for PE, patients identified …

The difference of free light chains as a predictor of kidney damage in patients with Multiple Myeloma

&#x0D; Background: Multiple myeloma (MM) is a malignant neoplasm characterized by the clonal expansion of plasma cells that can release monoclonal immunoglobulins (monoclonal component) or part of theme. Since 2001, the k and λ serum free light chains (sFLC) evaluation and their ratio (rFLC) have made up the laboratory analysis more sensitive and precise in MM patients. The role of rFLC has been widely studied and discussed and now it is validated in the literature. Instead, the value of free light chains difference (dFLC), especially in MM is less known yet. The aim of this study is to evaluate the relationship between the dFLC and the kidney damage parameters in patients with MM, in compa…

Second-line administration of thrombopoietin receptor agonists in immune thrombocytopenia: Italian Delphi-based consensus recommendations

Introduction: In patients with primary immune thrombocytopenia (ITP), a short course of steroids is routinely given as first-line therapy. However, the response is often transient and additional therapy is usually needed. Thrombopoietin receptor agonists (TPO-RAs) are frequently used as second-line therapy, although there is little clinical guidance on the timing of their administration and on tapering/discontinuation of the drug. To provide clinical recommendations, we used the Delphi technique to obtain consensus for statements regarding administration and on tapering/discontinuation of second-line TPO-RAs among a group of Italian clinicians with expertise in management of ITP. Methods: T…

Splenomegaly Impacts Prognosis in Essential Thrombocythemia and Polycythemia Vera: A Single Center Study

Splenomegaly is one of the major clinical manifestations of primary myelofibrosis and is common also in other chronic Philadelphia-negative myeloproliferative neoplasms, causing symptoms and signs and affecting quality of life of patients diagnosed with these diseases. We aimed to study the impact that such alteration has on thrombotic risk and on the survival of patients with essential thrombocythemia and patients with Polycythemia Vera (PV). We studied the relationship between splenomegaly (and its grade), thrombosis and survival in 238 patients with et and 165 patients with PV followed at our center between January 1997 and May 2019.

EFFECTIVENESS OF LOW DOSE ORAL VITAMIN K FOR PATIENTS WITH INR VALUES OF MORE THAN 10.0: RESULTS OF A PROSPECTIVE COHORT STUDY

Isolated Nodal TBC Reactivation in a Patient with Post-Thrombocythemia Myelofibrosis Treated with Ruxolitinib: Case Report and Review of the Literature

Ruxolitinib side effects include the most frequent hematological toxicity along with a more recently evidenced immunosuppressive activity, interfering both with the innate and adaptive immunity, and several cases of reactivation of latent infections by opportunistic agents in patients in treatment with ruxolitinib have been published in the last years. Several pathophysiological mechanisms may explain an association between ruxolitinib and opportunistic infections. From what we know, the only case of an isolated lymph node TBC reactivation in a ruxolitinib-treated myelofibrosis (MF) patient was reported by Patil et al. in 2016 [Int J Med Sci Public Health. 2017;6(3):1]. Other 10 cases descr…

Cryopreserved platelets: from in vitro thrombin generation potential to in vivo safety

Abstract Background: Cryopreservation of platelets (PLTs) at -80°C with dimethyl sulfoxide (DMSO) can extend their shelf life up to 2 years. Cryopreserved PLTs (CRY-PLTs) are reported to have a greater in vivo hemostatic effect than liquid-stored PLTs. Aims of this study were: i. to evaluate the thrombin generation potential of buffy coat derived cryopreserved PLTs (CRY- BC PLT) in comparison with fresh buffy coat derived platelets concentrates; ii. to determine the efficacy and safety of CRY-PLTs transfusion in hematological patients with severe thrombocytopenia. Materials and methods: BC PLTs were obtained from 5 buffy coats and pooled. The final PLTs concentrates were leukoreduced by fil…

Low molecular weight heparins in cancer patients: to treat thromboembolic events, the tumor, or both?

The interrelationship between cancer and thrombosis is well known. Recent data help physicians to optimize the management of thrombotic complications occurring in cancer patients. However, many issues are still uncertain. First, although the development of venous thromboembolism (VTE) in a patient with known cancer is the most common presentation, concerns remain about the optimal duration and dosages of anticoagulants. Questions also arise concerning the need to implement heparin prophylaxis in the course of chemotherapy. Secondly, in some patients, thrombosis precedes the diagnosis of malignancy. In this case, the question is whether or not to screen patients for an occult cancer. Thirdly…

LIMITED VERSUS EXTENDED ULTRASONOGRAPHY FOR THE DIAGNOSIS OF CLINICALLY SUSPECTED DEEP VEIN THROMBOSIS. A RANDOMIZED STUDY

The persistence of residual vein thrombosis, after an episode of deep vein thrombosis, and the risk of new overt cancer.

Immune Tolerance Induction in Hemophilia A: A Review

In this article, a comparative analysis of the data stemming from the studies conducted in the field of immune tolerance treatment (ITT) of hemophilia A was attempted. Comparisons are difficult because previous studies differ in many respects, including the dosage of factor (F) VIII, the number of FVIII administrations per day, the association with immunosuppressive drugs (prednisone, cyclophosphamide), and, most importantly, the definition of success in terms of the reacquisition of tolerance. However, a number of variables consistently influenced outcome: the inhibitor titer, either the maximum one or the one assayed before immune tolerance (IT) start and age. As to the FVIII dose, result…

First Interim Analysis of the Italian Dante Study: De-Escalation before Treatment-Free Remission in Patients with Chronic Myeloid Leukemia Treated with First-Line Nilotinib

Abstract Introduction: Treatment-free remission (TFR) in chronic myeloid leukemia (CML) is demonstrated to be achievable and recommended for patients (pts) in sustained deep molecular response (sDMR) who can discontinue tyrosine kinase inhibitor (TKI) treatment and maintain responses in ~50% of cases. While the feasibility and safety of TKI cessation have been largely demonstrated, the strategies of TFR optimization are yet to be clarified. Studies (eg. DESTINY) investigating de-escalation, mainly after imatinib, suggested that a stepwise approach may favor TFR outcome. We present the interim results of the phase 2, prospective, multicenter DANTE study (NCT03874858) evaluating de-escalation…

Role of clinical and laboratory parameters for treatment choice in patients with inherited FVII deficiency undergoing surgical procedures: evidence from the STER registry

Perioperative bleeding is a major concern in patients with factor VII (FVII) deficiency. Evaluating data of 95 FVII-deficient patients undergoing 110 surgical procedures (61 major, 49 minor), we assessed the impact of type of surgery, bleeding phenotype and FVII coagulant activity (FVII:C) levels on perioperative replacement therapy (RT). Compared to those with higher FVII:C levels, patients with &lt;3% FVII:C received a higher number of RT doses (8 vs. 2, P = 0·003) for a longer RT duration (3 days vs. 1 day, P = 0·001), with no difference in RT dose. Similarly, patients with a history of major bleeds received a higher number of RT doses (8·5 vs. 2-3, P = 0·013) for a longer RT duration (2…

Recombinant, activated factor VII for surgery in factor VII deficiency: a prospective evaluation - the surgical STER

Successful treatment of gastrointestinal bleeding with recombinant factor VIIa after kidney transplantation in patients with pancytopenia.

Abstract Hemostatic disorders can often complicate transplantation procedures. Moreover, antihemmorhagic drugs may not efficiently control bleeding that occurs in such cases. We report on a patient who underwent kidney transplantation complicated by bone marrow aplasia and gastric bleeding who was succesfully treated with recombinant activated FVII (Novoseven). In May 2005, a 53-year-old man affected by chronic renal insufficiency underwent kidney transplantation. At the beginning of June, laboratory tests showed progressive reduction in the blood cell count with anemia, granulocytopenia, and thrombocytopenia related to the development of marrow insufficiency. We commenced transfusion thera…

Platelet Cut-Off For Anticoagulant Therapy In Cancer Patients With Venous Thromboembolism and Thrombocytopenia: An Expert Opinion Based On RAND/UCLA Appropriateness Method (RAM)

Abstract Introduction Cancer-related Venous Thromboembolism (VTE) requires treatment with Low Molecular Weight Heparin (LMWH), which is more effective and safer than warfarin; however, the risk of major hemorrhage still remains clinically relevant (up to 5%). This rate is even higher in case of impaired hemostasis, such as during thrombocytopenia (due to myelosuppression or chemo-therapy) where the bleeding risk is directly related to the platelet count level. At the present, the best management of adult patients with acute or non-acute cancer-related VTE during thrombocytopenia is uncertain. Objective To develop a consensus about the platelet cut-off for a safe LMWH administration in cance…

ABSOLUTE LYMPHOCYTE COUNT IS NOT A PREDICTOR FOR SURVIVAL IN NEWLY DIAGNOSED ELDERLY PATIENTS WITH MULTIPLE MYELOMA

Markers della trombofilia nella arteriopatia cronica periferica ed eventi sichemici polidistrettuali

Deferment of Objective Assessment of Deep Vein Thrombosis and Pulmonary Embolism Without Increased Risk of Thrombosis

Background: Treatment of patients with suspected deep vein thrombosis (DVT) or pulmonary embolism (PE) is problematic if diagnostic imaging is not immediately available. Pretest clinical probability (PCP) and D-dimer assessment can be used to identify patients for whom empirical protective anticoagulation is indicated. To evaluate whether PCP and D-dimer assessment, together with the use of low-molecular-weight heparins (LMWHs), allow objective appraisal of DVT and PE to be deferred for up to 72 hours, patients with suspected DVT and PE were prospectively examined. Methods: Patients identified with a high PCP or a moderate PCP with positive D-dimer test results received a protective full-do…

Cellule staminali ematopoietiche circolanti come marker indipendente di buon outcome clinico in pazienti con beta talassemia

Cancer Patients Requiring Interruption of Long-Term Anticoagulant Therapy: The Use of Fixed Sub-Therapeutic Doses of Low-Molecular Weight Heparin

Abstract Abstract 1244 Introduction. We tested the efficacy and safety of fixed doses of Low-Molecular Weight Heparin (LMWH) in cancer patients requiring interruption of Vitamin-k Antagonist (VKA) because of invasive procedures (defined as major and non major surgery) or chemotherapy inducing platelets depletion. Methodology. Cancer patients were defined to be at high (atrial fibrillation [AF] with previous stroke, prosthetic mitralic valves and venous thromboembolism [VTE] lasting &lt; 3months) or low risk of thrombosis (AF without previous stroke, VTE lasted &gt; 3 months, and prosthetic aortic valves). They discontinued VKA 5 + 1days before surgery or chemotherapy; in those at low-risk f…

Residual Vein Thrombosis Assessment Establishes the Optimal Duration of Oral Anticoagulants in Patients with Idiopathic or Provoked Deep Vein Thrombosis: a Randomized, Controlled Trial

Immune Thrombocytopenia in Antiphospholipid Syndrome: Is It Primary or Secondary?

Antiphospholipid syndrome (APS) is frequently associated with thrombocytopenia, in most cases mild and in the absence of major bleedings. In some patients with a confirmed APS diagnosis, secondary immune thrombocytopenia (ITP) may lead to severe thrombocytopenia with consequent major bleeding. At the same time, the presence of antiphospholipid antibodies (aPL) in patients with a diagnosis of primary ITP has been reported in several studies, although with some specific characteristics especially related to the variety of antigenic targets. Even though it does not enter the APS defining criteria, thrombocytopenia should be regarded as a warning sign of a “high risk” APS and thus thoroughly ev…

Coronary artery stenosis treatment in aging patients with inherited Factor VII deficiency: Where do we stand?

Aging with rare bleeding disorders such as factor VII (FVII) deficiency poses several challenges to treatment because of the occurrence of cerebral and cardiovascular age-related comorbidities and high bleeding risks. We report a case of long-term treatment with antiplatelet agents and contemporary prophylaxis of bleeding in a woman affected by severe FVII deficiency diagnosed with symptomatic coronary artery stenosis. Information on the management of antithrombotic treatment in rare bleeding disorders is lacking and mainly limited to anecdotal reports or side effects secondary to replacement therapy. We also briefly reviewed available data on the treatment of arterial thrombosis in FVII de…

Can we compare haemophilia carriers with clotting factor deficiency to male patients with mild haemophilia?

Introduction Certain haemophilia carriers demonstrate an increased bleeding tendency, mainly related to clotting factor deficiency. No study has so far formally compared the bleeding phenotype of women and girls with mild FVIII or FIX deficiency and associated management with that of male patients affected by mild haemophilia A and B. Material and methods We retrospectively evaluated 44 women and girls with mild FVIII or FIX deficiency (FVIII or FIX 0.05-0.5 IU/mL) and 77 male patients with mild haemophilia A or B and compared them with respect to clotting factor level, age at and trigger for diagnosis, as well as treatment modalities. Results After excluding gender-related haemorrhagic sym…

Correlation between leukocytosis and thrombosis in Philadelphia-negative chronic myeloproliferative neoplasms

The evidence that leukocytes may contribute to the pathogenesis of thrombosis in Chronic Myeloproliferative Neoplasms is increasing but not definitive. To further enforces whether an increased leukocyte count is associated with thrombosis and whether this effect can be modulated by cytoreductive therapy, we analyzed the clinical course of 187 patients with Polycythemia Vera (PV) and Essential Thrombocythemia (ET) followed at two Italian Institutions over a period of 7 years. The association was measured at diagnosis or before thrombotic events: a multivariable analysis was carried out using data at baseline and time-dependent covariates. We found that white blood cells (WBC) count above 9.5…

Clinical history of thrombosis before diagnosis of overt myeloproliferative neoplasms in triple negative patients

Thromboses are the most important preventable risk factors for morbidity and mortality in myeloproliferative neoplasms (MPN). We here performed a retrospective cross sectional study of patients with a diagnosis of Philadelphia negative MPN and a prior history of thrombosis, analyzed from electronic charts. Among a cohort of 260 patients with MPNs (78PV, 102ET, 80 MF), forty four were found triple negative for JAK-2, calreticulin and MPL gene mutations. Sixty-nine (26.54%) patients (29F, 40M) had a personal past clinical history of arterial or venous thrombosis. Among patients with thrombosis, 13(18.8%) cases (11ET, 2MF) were triple negative (median age:60 years). Most events, in particular …

Incidence and Management Of Venous Thrombosis In Acute Leukemia: A Multicenter Study

Abstract Background Venous thrombosis (VT) frequently complicates the clinical course of cancer. Reported incidence of VT in many hematological neoplasms is up to 10%, a value comparable to that of solid tumors. Available data on the incidence and management of VT in Acute Leukemia (AL) are scanty and quite discordant. We have performed a multicenter retrospective study with the primary objective to evaluate the incidence of venous thrombotic complications in a population of patients with AL. Secondary objective was to evaluate the management of these complications in patients with AL. Materials and Methods Available clinical records of out and in-patients diagnosed with AL from January 200…

Personalized prophylaxis with simoctocog-alfa(human-cl rhFVIII):A real-life experience on children and moderate haemophilia A patients

JAK2 ALLELE BURDEN IN PATIENTS WITH PHILADELPHIA NEGATIVE MYELOPROLIFERATIVE NEOPLASMS

Tailoring haemophilia A prophylaxis with BAY 81-8973: A case series

BAY 81-8973 is an unmodified, full-length third generation recombinant factor VIII (rFVIII) which offers a more favorable pharmacokinetic (PK) profile, compared to its predecessor sucrose-formulated rFVIII (rFVIII-FS). We here report on a retrospective case series of nine patients affected by hemophilia A (HA), with variable disease severity, bleeding phenotype and comorbidities, to underline our clinical practice on prophylaxis with a recently introduced standard hall-life recombinant Factor VIII. The current case series highlights how the current clinical management of hemophilia is able to personalize treatment in several specific conditions like concomitant illnesses with thrombotic ris…

Familial essential thrombocythemia: 6 cases from a mono‐institutional series

Rarely essential thrombocythemia (ET) is diagnosed in more than one person within a family. Familial myeloproliferative neoplasms are underdiagnosed. In this report, we describe 6 couples of familial ET, evaluating the heterogeneity of the mutational state and the clinical presentation.

Buffy coat-derived platelets cryopreserved using a new method: Results from a pivotal clinical trial on thrombocytopenic patients with acute leukaemia

Abstract The administration of cryopreserved platelets (PLTs) may overcome the limits of platelet shortage and availability, especially during some seasons or in specific contexts like rural areas. After in vitro validation studies, ad hoc prepared buffy coat-derived pooled platelet concentrates (BC-PLTs), treated with dimethyl sulphoxide (DMSO) and cryopreserved (CRY BC-PLTs) at -80 °C with a modified Valeri method, were transfused in patients with severe thrombocytopenia secondary to chemotherapy for acute leukaemia (AL). Five inpatients were enrolled in the pivotal clinical trial NCT02032134: 4 males and 1 female with a mean age of 71 years (range: 65–80). Four patients were diagnosed wi…

Immunosenescence and lymphomagenesis

Abstract One of the most important determinants of aging-related changes is a complex biological process emerged recently and called “immunosenescence”. Immunosenescence refers to the inability of an aging immune system to produce an appropriate and effective response to challenge. This immune dysregulation may manifest as increased susceptibility to infection, cancer, autoimmune disease, and vaccine failure. At present, the relationship between immunosenescence and lymphoma in elderly patients is not defined in a satisfactory way. This review presents a brief overview of the interplay between aging, cancer and lymphoma, and the key topic of immunosenescence is addressed in the context of t…

Optimizing Tumor-Reactive &amp;#947;&amp;#948;T Cells for Antibody-Based Cancer Immunotherapy

Monoclonal antibodies (mAbs) constitute the most rapidly growing class of human therapeutics and the second largest class of drugs after vaccines. The treatment of B-cell malignancies and HER2/Neu+ breast cancer has benefited considerably from the use of therapeutic mAbs, either alone or in combination with standard chemotherapy. Frequent relapses, however, demonstrate that the bioactivity of these mAbs is still suboptimal. The concept of improving the anti-tumor activity of mAbs is well established and potentiating the cytotoxicity induced by anticancer mAbs can be achieved by strategies that target the downstream cytolytic effector cells. The recruitment of Fcγ receptor-dependent function…

Clinical experience with retrievable vena cava filters: results of a prospective observational multicenter study

Summary. Background: Retrievable inferior vena cava (IVC) filters offer the attractive possibility to be definitive or to be removed when they become unnecessary. Objective: The purpose of this study was to evaluate the efficacy and the likelihood to remove the retrievable IVC filter ALN. Methods: A total of 30 patients (13 males and 17 females, mean age 57 ± 15 years) underwent placement of ALN filters. Indications for implantation were acute venous thromboembolism (VTE) with a contraindication to anticoagulation in 26 cases (86%), primary prophylaxis after major trauma in two cases (7%) or before surgery in two patients with very high thromboembolic risk (7%). Results: The filter was succ…

Late onset of unilateral optic disk edema secondary to treatment with imatinib mesylate

Key Clinical Message Prompt ophthalmology evaluation and immediate imatinib suspension should be suggested at any time of tyrosine kinase inhibitor therapy in patients with visual deficit, as it may be a clinical manifestation of optic disk edema, and suspension may help in prompt recovery.

Clinical utility and physician perceptions of a digital platform for electronic patient-reported outcomes monitoring in patients with hematologic malignancies in real-world practice.

Abstract Background There is now great interest in using digital health tools to monitor patients' health status in real-world practice. Such tools often include electronic-patient-reported outcome (ePRO) systems in which symptoms questions are included into online interfaces for patient self-reporting, with real-time alerts triggered to the treating physician if severe symptoms or problems are reported. However, there is little information about the clinical utility and user perceptions of these systems, and this is particularly true in the area of hematology. Objectives This study investigates physicians' perceptions of usability and clinical utility of using remote ePROs in routine pract…

Antimicrobial prophylaxis in patients with immune thrombocytopenia treated with rituximab: a retrospective multicenter analysis

The primary aim of this study was to describe the use of primary anti-infective prophylaxis (AP) in common clinical practice in patients affected by immune thrombocytopenia (ITP) and treated with RTX. Population studied consisted of patients affected by ITP (age ≥ 18 years) who had received at least one dose of RTX from January 2008 to June 2018. Five Italian haematology centres participated in the current study. Data were retrospectively collected: demographic data (age, gender), concomitant comorbidities and previous therapies for ITP, characteristics of AP, the occurrence of infections and their management. The ITP cohort consisted of 67 patients sub-grouped into two categories according…

Reply to e.g. Urrego et Al.

The risk of recurrent cardiovascular events in patients with increased plasma homocysteine levels is reduced by short but not long-term therapy with folate and B vitamins.

Hyperhomocysteinemia is considered an independent risk factor for atherosclerosis, atherothrombosis and Venous ThromboEmbolism (VTE) [1], [2] and [3]. Normal total plasma homocysteine concentrations range from 5 to 15 μmol/L in the fasting state. Hyperhomocysteinemia is classified as moderate (homocysteine concentration, 15 to 30 μmol/L), intermediate (> 30 to 100 μmol/L), and severe (> 100 μmol/L) on the basis of concentrations measured during fasting. Although severe hyperhomocysteinemia is rare, mild hyperhomocysteinemia occurs in approximately 5% to 7% of the general population. In this case, patients are typically asymptomatic until the third or fourth decade of life when premature Cor…

La gestione dell'embolia polmonare non massiva: nuove evidenze sulla terapia

Effects of B-Cell Lymphoma on the Immune System and Immune Recovery after Treatment: The Paradigm of Targeted Therapy

B-cell lymphoma and lymphoproliferative diseases represent a heterogeneous and complex group of neoplasms that are accompanied by a broad range of immune regulatory disorder phenotypes. Clinical features of autoimmunity, hyperinflammation, immunodeficiency and infection can variously dominate, depending on the immune pathway most involved. Immunological imbalance can play a role in lymphomagenesis, also supporting the progression of the disease, while on the other hand, lymphoma acts on the immune system to weaken immunosurveillance and facilitate immunoevasion. Therefore, the modulation of immunity can have a profound effect on disease progression or resolution, which makes the immune syst…

Asymptomatic immunoglobulin light chain amyloidosis (AL) at the time of diagnostic bone marrow biopsy in newly diagnosed patients with multiple myeloma and smoldering myeloma. A series of 144 cases and a review of the literature

The rate of asymptomatic amyloidosis (AL) among patients with newly diagnosed multiple myeloma (MM) or smoldering multiple myeloma (SMM) is unknown. We evaluated number and clinical significance of asymptomatic AL in consecutive MM and SMM patients, not having recognition of symptomatic AL at the time of their diagnostic bone marrow biopsy. Bone marrow biopsies were stained with Congo red and considered diagnostic for AL in case of positive Congo red staining with apple-green birefringence. Biopsies from 144 patients were evaluated: 77 had a diagnosis of MM and 67 of SMM. The median age was 59 (range 26–84) years; the median follow-up was 76 months (range 0–216). Immunoglobulin isotypes wer…

Efficacy and safety during formulation switch of a pasteurized VWF/FVIII concentrate: results from an Italian prospective observational study in patients with von Willebrand disease

Summary Von Willebrand disease (VWD) is an inherited bleeding disorder caused by the quantitative or qualitative deficiency of von Willebrand factor (VWF). Replacement therapy with plasma-derived VWF/factor VIII (FVIII) concentrates is required in patients unresponsive to desmopressin. To assess the efficacy, safety and ease of use of a new, volume-reduced (VR) formulation of VWF/FVIII concentrate Haemate® P in patients requiring treatment for bleeding or prophylaxis for recurrent bleeding or for invasive procedures. Pharmacoeconomic variables were also recorded. Data were analysed using descriptive statistics. This was a multicentre, prospective, observational study. Consecutively enrolled…

Response to Urrego et al

Cancer-Associated Deep Vein Thrombosis: The Role of Residual Vein Thrombosis for Assessing the Duration of Low Molecular Weight Heparin (the EXTENDED Cancer-DACUS)

Abstract Introduction. The optimal duration of Low Molecular Weight Heparin (LMWH) after cancer associated deep vein thrombosis (DVT) is unknown; current guidelines suggest to prolong anticoagulation until cancer is active. We have recently demonstrated, in a randomized trial, that detection of Residual Vein Thrombosis (RVT) after 6 months of LMWH identify patients who require or not extension of therapy with anticoagulants (JCO in press). Now we present data of a prospective study evaluating a RVT-based management of patients with cancer-associated DVT, in whom LMWH has been extended up to 2 years in patients considered at high-risk for recurrent DVT because of persistence of RVT. Material…

Interim 18f-PDGPET for Aggressive Non-Hodgking's Lymphoma: A Systematic Review and Meta-Analysis

Abstract Abstract 5183 Background: The advantage of using interim 18F-fluorodeoxyglucose (FDG) positron-emission tomography (PET) scan in the clinical work-up of patients with non-Hodgkin's lymphoma (NLH) is unclear. Data from meta-analyses are inconclusive, mainly because of the low number of patients evaluated and heterogeneity among studies. New clinical investigations, focused on this topic, have been recently published. We conducted an updated systematic review on the role of 18PDG-PET for the interim evaluation in patients with aggressive lymphomas. Materials and Methods: Medline, Embase, Scopus and Databases were searched for relevant studies through March 2011. We included studies t…

Driver mutations and differential sensitivity to targeted therapies: a new approach to the treatment of lung adenocarcinoma

The adenocarcinoma of the lung has recently shown peculiar molecular characteristics, which relate with both carcinogenesis and response to targeted drugs. Several molecular alterations have been defined as "driver mutations". These are responsible for both the initiation and maintenance of the malignancy. The epidermal growth factor receptor (EGFR) pathway is the main regulator of cell function and cancer development. It has a widely defined role in the occurrence of driver mutations. Up till now EGFR gene mutations, KRAS gene mutations and EML4-ALK fusion genes are the most widely recognized alterations involved in both the biology and the clinical management of lung adenocarcinoma. In th…

Gastrointestinal bleeding due to angiodysplasia in patients with type 1 von Willebrand disease: report on association and management

Clinical and Morphologic Predictors of Outcome in a Multicenter Cohort of ITP Patients Treated with Trombopoietin Analogues

Abstract Background: The role of bone marrow response in patients with immune thrombocytopenia (ITP) has gained paramount importance since the last 10 years, with the demonstrations that marrow megakaryocytes (MGK) are unable to properly compensate platelets peripheral destruction. TPO receptor agonists (TPOa), namely romiplostim (ROMI) and eltrombopag (EPAG), by stimulating megakaryopoiesis are able to induce a response in 74% to 94% of cases in clinical trials. However, real world use of these drugs has shown frequent changes in individual dose requirement, the possibility of treatment discontinuation, and their effectiveness outside registered indications; moreover, nothing is known abou…

Paroxysmal nocturnal hemoglobinuria-like phenotype and thrombotic risk in several clinical disorders.

High Output Heart Failure in Multiple Myeloma: Pathogenetic Considerations.

The high output heart failure is a clinical condition in which the systemic congestion is associated to a high output state, and it can be observed in a non-negligible percentage of hematological diseases, particularly in multiple myeloma, a condition in which the risk of adverse cardiovascular events may increase, with a worse prognosis for patients. For this reason, though an accurate literature search, we provided in this review a complete overview of different pathogenetic mechanisms responsible for high output heart failure in multiple myeloma. Indeed, this clinical finding is present in the 8% of multiple myeloma patients, and it may be caused by artero-venous shunts, enhanced angioge…

Cardiovascular Issues in Tyrosine Kinase Inhibitors Treatments for Chronic Myeloid Leukemia: A Review

Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm driven by a fusion gene, encoding for the chimeric protein BCR-ABL, with constitutive tyrosine kinase activity. The use of tyrosine kinase inhibitors (TKIs) has drastically improved survival, but there are significant concerns about cardiovascular toxicity. Cardiovascular risk can be lowered with appropriate baseline evaluation, accurate choice of TKI therapy, improvement of modifiable cardiovascular risk factors through lifestyle modifications, and prescription of drugs for primary or secondary prevention. Which examinations are necessary, and when do they have to be scheduled? How often should a TKI-treated patient undergo wh…

Emotions and Opinions of Adult Patients with Haemophilia During the COVID-19 (Coronavirus Disease 2019) Pandemic Caused by SARS-CoV-2: A Monocentric Survey

Mariasanta Napolitano, 1 Maria Francesca Mansueto, 1 Davide Sirocchi, 1 Angelo Davide Contrino, 1 Simona Raso, 2 Sergio Siragusa 1 1Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), Haematology Unit, Reference Regional Centre for Thrombosis and Haemostasis, University of Palermo, Palermo, Italy; 2Division of Haematology, Department of Surgical, Oncological and Stomatological Disciplines (Di.Chir.On.S.), AOUP Paolo Giaccone, Palermo, ItalyCorrespondence: Mariasanta NapolitanoDepartment of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties (PROMISE), Haematology Unit, Reference Regional Centre for Thromb…

Thrombotic complications in paroxysmal nocturnal haemoglobinuria: a literature review.

Future directions in acquired hemophilia A

Residual vein thrombosis for assessing duration of anticoagulation after unprovoked deep vein thrombosis of the lower limbs: the extended DACUS study.

Abstract The safest duration of anticoagulation after idiopathic deep vein thrombosis (DVT) is unknown. We conducted a prospective study to assess the optimal duration of vitamin K antagonist (VKA) therapy considering the risk of recurrence of thrombosis according to residual vein thrombosis (RVT). Patients with a first unprovoked DVT were evaluated for the presence of RVT after 3 months of VKA administration; those without RVT suspended VKA, while those with RVT continued oral anticoagulation for up to 2 years. Recurrent thrombosis and/or bleeding events were recorded during treatment (RVT group) and 1 year after VKA withdrawal (both groups). Among 409 patients evaluated for unprovoked DVT…

Validation of the revised international prognostic scoring system (IPSS-R) in patients with myelodysplastic syndrome: a multicenter study.

The revised IPSS (IPSS-R) was developed aiming at a better prognostication, taking into account patients treated with best supportive care. We herein validated this model on the basis of data from 1314 patients who received BSC only as well as patients who underwent induction chemotherapy (n=214) or allogeneic transplantation (n=167). We could demonstrate a clear distinction of the IPSS-R risk categories with regard to survival and risk of AML evolution in all patient cohorts. When comparing IPSS-R, IPSS, WHO prognostic scoring system (WPSS) and Duesseldorf score, the best results regarding the ability to predict survival were obtained by the IPSS-R.

Comparison between thrombotic risk scores in essential thrombocythemia and survival implications.

The conventional thrombotic risk stratification in essential thrombocythemia (ET) distinguishes patients in two risk groups based on previous thrombosis and age (&lt; or &gt;60). The IPSET-thrombosis takes into account four risk factors: age greater than 60 years and the presence of CV risk factors, thrombosis history and JAK2 V617F presence. The revised IPSET-thrombosis uses three adverse variables to delineate four risk categories: age greater than 60, thrombosis history, and JAK2 V617F presence. We compared different risk models in the estimation of thrombotic risk in 191 patients with ET and the role of specific driver mutations affecting overall survival, according to thrombotic risk. …

Residual vein thrombosis assessment establishes the otpimal duration of oral anticoagulants in patients with idiopathic or provoked deep vein thrombosis

Safety of plasma-derived protein C for treating disseminated intravascular coagulation in adult patients with active cancer

Cancer-related disseminated intravascular coagulation (DIC) is a life-threatening condition for which no effective treatment is currently available. Protein C (PC), a modulator of coagulation as well as the inflammatory system, has been successfully tested (in its activated recombinant form [a-rPC]) in sepsis-related coagulopathy, but with an increased risk for major bleeding. Plasma-derived PC (pd-PC) is more suitable than a-rPC in patients at high risk from bleeding due to its self-limiting process. We carried out a single-arm study evaluating the role of pd-PC in adult cancer patients with overt DIC. Over a period of 3 years, we treated 19 patients with overt DIC and a PC plasma concentr…

Natural history of mesenteric venous thrombosis in patients treated with vitamin K antagonists: a multi-centre, retrospective cohort study.

summaryKnowledge on the natural history of mesenteric vein thrombosis (MVT) and of the efficacy and safety of long-term oral anticoagulant therapy (OAT) in this setting is based on small uncontrolled series of patients with a limited follow-up. It was the aim of the study to assess the natural history of MVT in a cohort of patients treated with OAT. The charts of all MVT patients currently attending or who have attended four anticoagulation clinics were reviewed. Information on risk factors, treatment, recurrence, major bleeding and mortality was collected. Seventyseven patients (mean age 49.2 years; 45 males) were included with a median follow-up of 36 months (range 2–204 months). Forty-si…

Hemorheological parameters in Monoclonal Gammopathy of Undetermined Significance (MGUS).

There is scarcity of information about the hemorheological pattern in subjects with Monoclonal Gammopathy of Undetermined Significance (MGUS). This preliminary research is focused on the behaviour of whole-blood and plasma viscosity, haematocrit and erythrocyte deformability in the above clinical condition. We enrolled 21 MGUS subjects (10 women and 11 men; mean age 66.4 ± 11.6 years). In fasting venous blood we examined whole-blood and plasma viscosity at high and low shear rates, haematocrit, the ratios between whole-blood viscosity (at high and low shear rate) and haematocrit × 100, the ratio between plasma viscosity at low and high shear rate, and the erythrocyte deformability expressed…

The Role of Gemtuzumab Ozogamicin in Elderly AML Patients in Complete Remission.

Abstract The majority of patients (pts) with acute myeloid leukemia (AML) are diagnosed in their 6th and 7th decade of life. AML in elderly pts is associated with poor response to conventional chemotherapy and limited long-term survival, reflecting a higher incidence multidrug resistance mechanisms, a low bone marrow reserve which may prevent/delay the recovery of hematopoiesis after treatment, and the occurrence of co-morbidities. Gemtuzumab ozogamicin (GO) is an immunoconjugate with a humanized anti-CD33 that after internalization, releases a cytotoxic drug, calicheamicin; ≥80% of AML pts have myeloid blast cells that express the CD33 surface antigen. GO as a single agent has low antileuk…

Cardiovascular Toxicity in Cancer Patients Treated with Tyrosine Kinase Inhibitors: A Real-World Single-Center Experience

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Target therapy can cause various cardiovascular complications. The aim of this study was to evaluate the burden of cardiovascular complications related to treatment with anti-BCR-ABL tyrosine kinase inhibitors (TKIs) and to determine if there are differences between the latest- and first-generation TKIs. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; A retrospective observational study was carried out on 55 patients (39 men, 16 women; mean age ± SD: 58 ± 11 years) treated with TKIs targeting Bcr-Abl for a median period of 3.5 years. Patients were divided in two groups according to the type of treatment. Group A included patients treated with…

EFFECTIVENESS OF LOW DOSE ORAL VITAMIN K FOR PATIENTS WITH ELEVATED INR VALUES: RESULTS OF RANDOMIZED TRIAL EXAMINING CLINICAL OUTCOMES

Residual vein thrombosis assessment estabilishes the optimal duration of oral anticoagulants in patients with idiopatic or provoked deep vein thrombosis

The incidence of heparin-induced thrombocytopenia in medical patients treated with low-molecular-weight heparin: a prospective cohort study.

AbstractIn contrast with extensive documentation in patients treated with unfractionated heparin (UFH), the incidence of heparin-induced thrombocytopenia (HIT) in medical patients receiving low-molecular-weight heparin (LMWH) is less well defined. In a prospective cohort study, the platelet count was monitored in 1754 consecutive patients referred to 17 medical centers and treated with LMWH for prophylaxis or treatment of thromboembolic disorders. The diagnosis of HIT was accepted in case of a platelet drop of at least 50%, the absence of obvious explanations for thrombocytopenia, and the demonstration of heparin-dependent IgG antibodies. HIT developed in 14 patients (0.80%; 95% CI, 0.43%-1…

Efficacy of ruxolitinib retreatment in a patient with high-risk myelofibrosis using the international prognostic scoring system

Primary myelofibrosis (PMF) is a myeloproliferative neoplasm in which clonal proliferation of hematopoietic stem cells and bone marrow fibrosis coexist.1 Patients may eventually die due to leukemic progression, which occurs in up to 20% of cases, or because of cardiovascular comorbidities or cytopenia, which causes susceptibility to infections and bleeding.2 Myelofibrosis diagnosis relies upon the evaluation of several clinical and laboratory criteria suggested by the World Health Organization (WHO) in 2016.3 The major mutations leading to myelofibrosis usually occur in the JAK2, CALR, and MPL genes. However, in almost 10% of the cases, none of the above-mentioned mutations can be detected …

Le emergenze emorragiche in ematologia

Superficial venous thrombosis and spreading to deep veins: role of genetic risk factors for venous thromboembolism

Cancer patients requiring interruption of long-term warfarin because of surgery or chemotherapy induced thrombocytopenia: The use of fixed sub-therapeutic doses of low-molecular weight heparin

No data are available regarding the management of cancer patients requiring interruption of long-term vitamin-K antagonist (VKA) therapy. For this purpose, we tested the efficacy and safety of fixed doses of low-molecular weight heparin (LMWH) in substitution of VKA because of invasive procedures or chemotherapy-induced thrombocytopenia. In cancer patients on VKA, therapy was discontinued 5 ± 1 days before surgery or chemotherapy. Heparin was given at prophylactic dosage in patients at low risk and at fixed subtherapeutic doses (3,800 or 4,000 UI anti-FXa, b.i.d.) in those at high-risk for thrombosis. LMWH was reinitiated 12 hr after surgery and VKA the day after. In patients receiving chem…

Triple-Negativity Identifies a Subgroup of Patients with Better Overall Survival in Essential Thrombocythemia

Essential thrombocythemia, as defined by the WHO in 2016, is a Philadelphia-negative chronic myeloproliferative neoplasm showing a better prognosis than polycythemia vera and myelofibrosis. In a variable percentage, patients with essential thrombocythemia show none of the known driver-gene mutations that may occur on JAK2, CALR, and MPL genes. Such patients are classified as triple-negative and their clinical features and prognosis have not been described with precision yet. In this study, we evaluated some of the characteristics of this population by comparing them with those of patients with driver-gene mutated ET. Data from 266 consecutive essential thrombocythemia patients were analysed…

Management of Venous Thromboembolism (VTE) in Patients with Acute Leukemia: Results from a Multicenter Study

Abstract Background In the last decades, evaluation of thrombotic complications secondary to acute leukemia (AL) has been poorly investigated. Only scant data are available on management and prevention of thrombosis in this setting. We performed a multicenter retrospective study with the aim to evaluate the management of venous thromboembolism (VTE) in patients with AL and to report the most commonly adopted regimens of treatment. Materials and methods Available clinical records of out and in-patients diagnosed with AL from January 2008 to June 2013 in 7 Reference Regional Hospitals were analyzed. Cases of VTE, including thrombosis in atypical sites [Retinal occlusion (RO) and Cerebral Sinu…

The important impact of dental care on haemostatic treatment burden in patients with mild haemophilia

Background: Mild haemophilia (MH) is mainly characterized by haemorrhages secondary to surgery/invasive procedures or trauma. Haemostatic treatment in MH ranges from on demand to short prophylaxis according to the type of bleeding events and the basal clotting factor level. Oral surgery and dental extractions can represent a frequent haemostatic challenge in MH requiring appropriate treatment. However, only few studies on limited numbers of patients are available in the literature regarding the implications of dental management in patients with MH. Objectives: The purpose of the study was to evaluate the impact of dental care on the burden of haemostatic treatment in patients affected by MH…

Essential thrombocythemia: Biology, clinical features, thrombotic risk, therapeutic options and outcome

Prevention of venous thromboembolic events occurring in myeloma patients treated with second-generation novel agents

Thrombosis and neoplasms are strictly linked, and the diagnosis of a malignancy is a relevant risk factor for venous thromboembolism (VTE). In particular, between gammopathies, the VTE risk is known to be increased in both monoclonal gammopathy of uncertain significance and in multiple myeloma, with a 3- and 9-fold increase respectively, when compared to the general population. The risk appears to be further increased in patients treated with immunomodulating drugs, such as thalidomide, especially when in combination with dexamethasone or conventional cytotoxic chemotherapies, and lenalidomide. In 2008 the International Myeloma Working Group put out thrombosis prophylaxis recommendations fo…

Limited versus extended ultrasonography for the diagnosis of clinically suspected deep vein thrombosis

Managing Bleeding Complications in Patients Treated with the Old and the New Anticoagulants

An increasing number of patients receive anticoagulant therapy to prevent and treat arterial or venous thromboembolism. The major complication of anticoagulant therapy is the increase of the individual bleeding risk. All anticoagulant drugs can cause haemorrhages, that can sometimes be life-threatening. Although heparins and the vitamin K antagonists have been the most widely used anticoagulants for decades, the correct management of bleeding complications associated with these agents has been poorly studied. More recently, new anticoagulant drugs, both parenteral and oral, have been approved for clinical use. Currently, none of these new agents has a specific antidote, and little advise ca…

Factor VII Deficiency: Clinical Phenotype, Genotype and Therapy

Factor VII deficiency is the most common among rare inherited autosomal recessive bleeding disorders, and is a chameleon disease due to the lack of a direct correlation between plasma levels of coagulation Factor VII and bleeding manifestations. Clinical phenotypes range from asymptomatic condition—even in homozygous subjects—to severe life-threatening bleedings (central nervous system, gastrointestinal bleeding). Prediction of bleeding risk is thus based on multiple parameters that challenge disease management. Spontaneous or surgical bleedings require accurate treatment schedules, and patients at high risk of severe hemorrhages may need prophylaxis from childhood onwards. The aim of the c…

How should we determine length of anticoagulation after proximal deep vein thrombosis of the lower limbs?

The current approach for deciding the duration of vitamin K antagonist (VKA) treatment after an episode of venous thrombo-embolism (VTE) is mainly based on the characteristic of the index event (3 months or longer in case of unknown/persistent risk factors, 3 months or less in case of removable causes). However, the length of anticoagulation should be tailored on the patient's risk for recurrent thrombosis as well as for bleeding, but such 'time for decision' is often unclear and the optimal duration of VKA remains debatable. The presence of persistent residual vein thrombosis and increased D-dimer levels after stopping therapy are predictors for recurrent deep vein thrombosis (DVT). Manage…

Management of venous thromboembolism in patients with acute leukemia at high bleeding risk: a multi-center study

In the last decades, evaluation of clinically relevant thrombotic complications in patients with acute leukemia (AL) has been poorly investigated. The authors performed a multi-center study to evaluate the management of symptomatic venous thromboembolism (VTE) in adult patients with AL. The intention was to find as clinically relevant the following: symptomatic Venous Thrombosis (VT) occurred in typical (lower limbs) and atypical (cerebral, upper limbs, abdominal, etc) sites with or without pulmonary embolism (PE). Over a population of 1461 patients with AL, 22 cases of symptomatic VTE were recorded in hospitalized patients with a mean age of 54.6 years. The absolute incidence of VTE was 1.…

Red blood cell deformability in multiple myeloma1.

The aim of this study was the evaluation of the erythrocyte deformability in multiple myeloma (MM). We enrolled 29 MM patients and we evaluated, on fasting venous blood, the erythrocyte deformability, expressed as elongation index, and examined using the diffractometric method. By comparing normal controls and MM patients, a significant decrease in erythrocyte deformability, especially at low shear stresses, was found. In this research paper we evaluated all the hypothesis for a possible explanation of the behaviour of red blood cell deformability in MM, even considering how the alteration of erythrocyte deformability worsens the microcirculatory flow in these patients in association with t…

How Epidemiology of Polycythemia Vera Has Changed in the Last 10 Years: Results From the Whole Prospective Cohort of Patients in Cyto-PV Trial As Compared with Eclap Prospective Cohort

Abstract Abstract 1748 Introduction: Polycythemia vera (PV) is a chronic myeloproliferative neoplasms characterized by erythrocytosis, vasomotor disturbances, pruritus, risk of disease progression into acute myeloid leukemia or myelofibrosis and cardiovascular events, the last representing the main cause of morbidity and mortality. Since 2005 the V617F point mutation in Janus Kinase 2 (JAK2) gene gained a dominant role in determining the molecular basis and the diagnosis of PV. We compared the clinical epidemiology of the 1638 patients included in the ECLAP trial in the years 1997 to 2001, with that of a “modern” cohort of 365 PV, JAK2-positive patients included in the Italian CYTO-PV rando…

Thrombotic risk in paroxysmal nocturnal hemoglobinuria-like (PNH-like) phenotype

The complement system is an essential component of the innate immune defence that, if overly activated, may damage organs and tissues. For this reason, there is a fine complement regulatory system. The complement modulation system includes two proteins with important regulatory activity, CD55 or decay accelerating factor (DAF) and CD59 or membrane inhibitor of reactive lysis (MIRL). The paroxysmal nocturnal hemoglobinuria (PNH) is a clonal and non-neoplastic disease characterized by intravascular haemolysis, occurrence of thrombosis and bone marrow failure. In clinical practice, in opposition to PNH, a variety of pathological conditions have been observed with an acquired and non-genetic de…

CARDIOVASCULAR RISK IN ESSENTIAL THROMBOCYTHEMIA AND POLYCYTHEMIA VERA: THROMBOTIC RISK AND SURVIVAL

Thromboembolic and bleeding events pose a severe risk for patients with Polycythemia Vera (PV) and Essential Thrombocythemia (ET). Many factors can contribute to promoting the thrombotic event due to the interaction between platelets, leukocytes, and endothelium alterations. Moreover, a significant role can be played by cardiovascular risk factors (CV.R) such as cigarette smoking habits, hypertension, diabetes, obesity and dyslipidemia. In this study, we evaluated the impact that CV.R plays on thrombotic risk and survival in patients with PV and ET .

Fostering drug.storage,preparation and treatment modalities improves adherence to treatment with turoctocog-alfa in patients with haemophilia A:results from a short term follow-up

Using pharmacokinetics for tailoring prophylaxis in people with hemophilia switching between clotting factor products: A scoping review.

Abstract The objective of this scoping review is to summarize the current use of pharmacokinetics for tailoring prophylaxis in hemophilia patients switching between clotting factor products. Patients with hemophilia may require switching of clotting factor concentrates due to a variety of factors, but there have been perceived risks associated with switching, such as inhibitor development or suboptimal protection due to inadequate dosing while titrating treatment. Studies that look at patients switching from one clotting factor concentrate to another are categorized in terms of their primary and/or secondary objectives, notably biosimilarity and comparative pharmacokinetic studies and inhib…

Bleeding prophylaxis in a child with cleft palate and factor VII deficiency: a case report.

Bleeding prophylaxis in a child with cleft palate and factor VII deficiency: a case report. Pirrello R, Siragusa S, Giambona C, D'Arpa S, Cordova A, Moschella F. Source Dipartimento di Discipline Chirurgiche ed Oncologiche, Sezione di Chirurgia Plastica e Ricostruttiva, Università di Palermo, Palermo, Italy. Abstract The association between factor VII deficiency and cleft palate has never been described. The case of a child with cleft palate and factor VII deficiency who successfully underwent palatoplasty is described in this article. To allow surgical treatment, through maintenance of a normal prothrombin time, the patient was given 15 microg/kg of recombinant factor VIIa every 12 hours, …

Incidence of thromboembolic complications in patients with mechanical heart valves with a subtherapeutic international normalized ratio.

Objective Subtherapeutic international normalized ratios are frequently encountered in clinical practice, and patients with mechanical heart valves with inadequate anticoagulation may be exposed to an increased risk of thromboembolic events. There are no data on thromboembolic event risk for these patients. Methods We assessed the current practice patterns in the management of patients with mechanical heart valves with subtherapeutic international normalized ratios and assessed the risk of thromboembolic complications in this setting. The charts of patients with mechanical heart valves followed up in two anticoagulation clinics were reviewed. Patients with a history of stable, therapeutic a…

In-vitro NET-osis induced by COVID-19 sera is associated to severe clinical course in not vaccinated patients and immune-dysregulation in breakthrough infection

AbstractSince neutrophil extracellular traps formation (NET-osis) can be assessed indirectly by treating healthy neutrophils with blood-derived fluids from patients and then measuring the NETs response, we designed a pilot study to convey high-dimensional cytometry of peripheral blood immune cells and cytokines, combined with clinical features, to understand if NET-osis assessment could be included in the immune risk profiling to early prediction of clinical patterns, disease severity, and viral clearance at 28 days in COVID-19 patients. Immune cells composition of peripheral blood, cytokines concentration and in-vitro NETosis were detected in peripheral blood of 41 consecutive COVID-19 inp…

A Large-Scale Trial Testing the Intensità of CYTOreductive Therapy to prevent Cardiovascular Events in Patients with Polycythemia Vera (CYTO-PV trial).

Abstract Abstract 4 Introduction Current treatment recommendations in polycythemia vera (PV) have emphasized to maintain the hematocrit (HCT) values &lt;0.45 based on hemorrheological notions, results of a few small observational retrospective studies and consensus of experts. However, post-hoc analysis of two large randomized clinical trials (namely PVSG-1 and ECLAP) failed to show a different incidence of major thrombosis when HCT levels were kept in the range between 0.40 and 0.50. So far, no randomized clinical trial has provided evidence-based data assessing the usefulness of tight HCT control in reducing thrombosis. Thus, uncertainty of the optimal HCT target exists in clinical practi…

The Essential Thrombocythemia, Thrombotic Risk Stratification, and Cardiovascular Risk Factors

Essential thrombocythemia is a rare hematological malignancy with good overall survival, but moderate to high risk of developing arterial or venous thrombosis lifelong. Different thrombotic risk scores for patients with essential thrombocythemia have been proposed, but only one of them (the IPSET-t scoring system) takes into account the classical cardiovascular risk factors as one of the scoring items. Currently, in clinical practice, the presence of cardiovascular risk factors in patients with diagnosis of ET rarely determines the decision to initiate cytoreductive therapies. In our study, we compared different risk models to estimate the thrombotic risk of 233 ET patients and the role of …

Aspirin After Oral Anticoagulants for Prevention of Recurrence in Patients with Unprovoked Venous Thromboembolism. the Warfasa STUDY

Abstract Abstract 543 Background A recurrence occurs in 15–20% of patients with unprovoked venous thromboembolism (VTE) in the two years after the withdrawal of oral anticoagulant treatment. Extending anticoagulant treatment is effective but associated with increased bleeding risk. We assessed the efficacy and safety of aspirin for the prevention of VTE recurrence after a conventional course of oral anticoagulation. Methods Warfasa was an investigator-initiated double-blind randomized placebo-controlled event-driven study. Patients with a first-ever unprovoked VTE who had completed 6–12 months of oral anticoagulant treatment were randomized to receive aspirin, 100 mg daily, or placebo for a…

Polycythemia Vera as a Predisposing Factor for Aortic Stenosis: Prevalence and Correlation with Blood Cells Count and Mutational Status

Abstract The association between Polycythemia Vera (PV) and thrombosis is multi-factorial involving the complex interaction between activated leukocytes, platelets and endothelium. Recent reports have postulated that PV patients may over express adhesive molecules on red cell surface, likely by JAK2 mutation (Wautier M et al. Blood.2007;110(3):894–901). This process activates endothelium with production of vascular growth factors and other mechanisms leading to atherosclerosis. Aortic Stenosis (AS) is the commonest valvular heart disease in western countries; its pathogenesis is mainly related to a degenerative process sharing many characteristics with atherosclerosis. At the present is not…

Evaluation of Bone Marrow CD8+ tissue-Resident Memory T Cells in Multiple Myeloma

Background: CD8+ T cell responses are an essential component of the adaptive immune system. After resolution of infection a small population of memory cells is formed. In relation to circulatory patterns, different subsets of memory CD8+ T cells can be identified: the central memory (CM) and the effector memory T cells (EM) (Martin MD, et al., Front Immunol. 2018). In addition, it has been described a subset of resident memory T cells (TRM) permanently living in peripheral tissues, including the bone marrow (BM) (Di Rosa F., et al., Nat Rev Immunol. 2016). It is conceivable that these cells can contribute to the defence toward haematological tumours infiltrating the BM. Therefore, we perfor…

Lung Immune and Coagulative Host Response in Patients With Acute Exacerbations of Chronic Obstructive Pulmonary Disease (aeocpd).

Deferral of assessment of pulmonary embolism

We evaluated a simplified algorithm for safely postponing diagnostic imaging for pulmonary embolism (PE). At the index visit, patients were identified as being at high or low risk of PE; the former received full dosage low molecular weight heparin while the latter were left untreated until performance of diagnostic imaging (max 72 hours). During this period, no thromboembolic events occurred in low-risk patients (0/211, 0.% [upper 95% CI 0.9%]); only one event occurred in those at high-risk (1/125, 0.8% [upper 95% CI, 1.2]). Our study demonstrates that diagnostic imaging for PE can be safely deferred for up to 3 days.

Deep vein thrombosis and pulmonary embolism can be treated at home in cancer patients

Functional In Vitro Studies Of Buffy Coat Pooled Platelets Cryopreserved In Dimethyl-Sulphoxide With a New System

Abstract Introduction Cryopreservation for long term storage of platelets (PLTs) represents a clinical useful method for avoiding platelet shortage. Many studies have tried to define, in vitro and in vivo, the entity and weight of storage-related PLTs lesions with discordant results related to different methods. We have performed an in vitro prospective study to evaluate PLTs count, viability and function of buffy coat derived pooled platelet concentrates (BC-PLTs) treated with dimethyl-sulphoxide (DMSO) and cryopreserved at -80°C with an innovative patented system not requiring laminal flow hoods and external manipulations. Materials and methods Each BC-PLTs was obtained from 5 buffy coats…

Paroxysmal nocturnal haemoglobinuria: When delay in diagnosis and long therapy occurs

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal disorder characterized by hemolytic anemia, bone marrow failure and thrombosis, caused by a somaticmutation in PIG-A gene that results in theabsence of CD55 and CD59, two important complement regulatory proteins. In thispaper, a case of PNH is retrospectively examined looking for clinical and laboratory features, and the entire course of the disease from the onset of the symptoms isdescribed, together with an adequate follow-up over a 7-years treatment period. Inthis case, the not specificity and the limited clinical relevance of the symptoms led to adelay in diagnosis. After thrombosis, Eculizumab therapy has been shown to be effec…

Erythrocyte deformability in Polycythemia Vera

Patients requiring interruption of long-term oral anticoagulant therapy: the use of fixed sub-therapeutic doses of low-molecular weight heparin.

Introduction: We tested the efficacy and safety of fixed doses of Low-Molecular Weight Heparin (LMWH) in patients requiring interruption of Vitamin-k Antagonist (VKA) because of invasive procedures Methodology: Pre-operatively, patients discontinued VKA 5 +/- 1days; in those at low-risk for thrombosis, LMWH was given at a prophylactic dosage of 3.800 U.I. (nadroparin) or 4.000 U.I. (enoxaparin) anti-FXa once daily the night before the procedure. In patients at high-risk for thrombosis, LMWH was started early after VKA cessation and given at fixed sub-therapeutic doses (3.800 or 4.000 UI anti-FXa twice daily) until surgery. Post-operatively, LMWH was reinitiated 12 hours after procedure whil…

Factors associated with the timing of diagnosis of venous thromboembolism: results from the MASTER registry

INTRODUCTION: Signs and symptoms of venous thromboembolism (VTE) are non-specific and thus can make diagnosis difficult, even for an experienced clinician. We aimed to evaluate the timing of diagnosis of deep vein thrombosis (DVT) and pulmonary embolism (PE) in Italian hospitals and to identify individual and clinical predictors of timely or delayed diagnosis. MATERIAL AND METHODS: MASTER is a multicenter prospective registry of patients with acute DVT and PE. Information on clinical presentation and diagnostic methods, temporary and permanent risk factors, were captured by an electronic data network at the time of the index event. RESULTS: Data on 2047 patients (1024 males), 1505 with DVT …

Long-term risk of recurrent venous thromboembolism among patients receiving extended oral anticoagulant therapy for first unprovoked venous thromboembolism:A systematic review and meta-analysis

Background: The long-term risk for recurrent venous thromboembolism (VTE) during extended anticoagulation for a first unprovoked VTE is uncertain. Objectives: To determine the incidence of recurrent VTE during extended anticoagulation of up to 5 years in patients with a first unprovoked VTE. Methods: MEDLINE, EMBASE, and the Cochrane CENTRAL were searched to identify randomized trials and prospective cohort studies reporting recurrent VTE among patients with a first unprovoked VTE who were to receive anticoagulation for a minimum of six additional months after completing ≥3 months of initial treatment. Unpublished data on number of recurrent VTE and person-years, obtained from authors of in…

Superficial venous thrombosis: role of genetic risk factors on spreeding to deep veins

ABSOLUTE LYMPHOCYTE COUNT AS PREDICTOR FOR SURVIVAL IN NEWLY DIAGNOSED ELDERLY PATIENTS WITH MULTIPLE MYELOMA

Coexistence of Von Willebrand disease and gastrointestinal stromal tumor (G.I.S.T): Case report of a rare and challenge association

Von Willebrand disease (VWD) is the most common inherited bleeding disorder and is caused by a quantitative (type 1 and 3) or qualitative (type 2) defect of Von Willebrand factor (VWF). Bleeding from the gastrointestinal (GI) tract is not uncommon in VWD and is usually associated with angiodysplasia. We report herein on the management of a patient affected by VWD2B with severe GI bleeding secondary to gastrointestinal stromal tumor (GIST) complicated by deep vein thrombosis (DVT). The current case demonstrated that the hemostatic balance, in RBDs under specific circumstances, can range from a tendency toward a hemorrhagic to normal or prothrombotic state. In these patients, a close collabor…

Erythrocyte deformability and hemorheological profile in multiple myeloma

The hemorheological profile in multiple myeloma (MM) has been extensively studied. Our investigation regarded the behavior of whole-blood viscosity, plasma viscosity and erythrocyte deformability in MM. We enrolled 24 MM patients; 13 of them had been recently diagnosed and were at the initial stage of therapy, 6 were on consolidation/conservation therapy and 5 had achieved a complete remission. On fasting venous blood we evaluated whole-blood and plasma viscosity at high and low shear rates, haematocrit, the ratios between whole-blood viscosity (at high and low shear rate) and haematocrit×100, the ratio between plasma viscosity at low and high shear rate and the erythrocyte deformability ex…

EGFR genomic alterations in cancer: prognostic and predictive values.

The role of EGFR in cancer development and progression has been recognized for long time in a variety of human malignancies including lung, head and neck, colon, breast, ovary and glioma. Recently its role as a target of antineoplastic agents has also been identified and a variety of EGFR-targeted drugs is already being used in a clinical setting and others are at present under investigation. Many data involving EGFR protein expression are now available for the choice of anti-EGFR monoclonal antibodies in colorectal cancer and with regard to EGFR gene mutations for the choice of tyrosine kinase inhibitors in lung cancer. Other EGFR-related molecular factors, including the EGFR gene copy num…

Refined cytogenetic-risk categorization for overall and leukemia-free survival in primary myelofibrosis: a single center study of 433 patients.

We have previously identified sole +9, 13q- or 20q-, as 'favorable' and sole +8 or complex karyotype as 'unfavorable' cytogenetic abnormalities in primary myelofibrosis (PMF). In this study of 433 PMF patients, we describe additional sole abnormalities with favorable (chromosome 1 translocations/duplications) or unfavorable (-7/7q-) prognosis and also show that other sole or two abnormalities that do not include i(17q), -5/5q-, 12p-, inv(3) or 11q23 rearrangement are prognostically aligned with normal karyotype, which is prognostically favorable. These findings were incorporated into a refined two-tired cytogenetic-risk stratification: unfavorable and favorable karyotype. The respective 5-y…

Persistance of residual vein thrombosis after an episode of deep vein thrombosis of the lower limbs and the risk of new cancer and cardiovascular disease.

8531 Background: In patients with a first episode of idiopathic or provoked Deep Vein Thrombosis (DVT), the presence of Residual Vein Thrombosis (RVT), detected by UltraSonography (US) at the 3rd month from the index DVT, is an independent risk factor for developing recurrent Venous Thromboembolism (VTE) in the subsequent 2 years. Its absence can safely permit to stop Oral Anticoagulants (OA). At the present, it is unknown whether RVT may also identify patients at increased risk for developing cancer and/or cardiovascular disease (CD). In patients with previous DVT of the lower limbs, we conducted a prospective study for evaluating the correlation between RVT findings and the risk of new c…

Network meta-analysis of randomized trials in multiple myeloma: Efficacy and safety in frontline therapy for patients not eligible for transplant

The treatment scenario for newly-diagnosed transplant-ineligible multiple myeloma patients (NEMM) is quickly evolving. Currently, combinations of proteasome inhibitors (PI) and/or immunomodulatory drugs (IMiD) +/- the monoclonal antibody Daratumumab are used for first-line treatment, even if head-to-head comparisons are lacking. To compare efficacy and safety of these regimens, we performed a network meta-analysis (NMA) of 27 phase 2/3 randomized trials including a total of 12935 patients and 23 different schedules. Four efficacy/outcome and one safety indicators were extracted and integrated to obtain (for each treatment) the surface under the cumulative ranking-curve (SUCRA), a metric use…

Erythrocyte deformability profile evaluated by laser diffractometry in patients with multiple myeloma: Re-examination of our cases.

Background: Multiple myeloma is a complex pathology which represents about 10 % of all hematological neo-plasms. It can often present changes in the hemorheological profile and, in relation to this last topic, our aim is to evaluate the hemorheological profile in a group of multiple myeloma patients, with reference to erythrocyte deformability. Methods: We have examined the profile of the erythrocyte deformability in multiple myeloma enrolling 29 pa-tients; this profile, expressed as elongation index at several shear stress, has been obtained using the diffracto-metric method. Results: By comparing normal controls and MM patients, a significant decrease in erythrocyte deformability, especia…

Optimal duration of low molecular weight heparin for the treatment of cancer-related deep vein thrombosis. The ”CANCER DACUS” study

Purpose We evaluated the role of residual vein thrombosis (RVT) to assess the optimal duration of anticoagulants in patients with cancer who have deep vein thrombosis (DVT) of the lower limbs. Patients and Methods Patients with active cancer and a first episode of DVT treated with low molecular weight heparin (LMWH) for 6 months were eligible. Patients were managed according to RVT findings: those with RVT were randomly assigned to continue LMWH for an additional 6 months (group A1) or to discontinue it (group A2), and patients without RVT stopped LMWH (group B). The primary end point was recurrent venous thromboembolism (VTE) during the 1 year after disconinuation of LMWH, and the secondar…

Review: Long-term anticoagulation reduces recurrent venous thromboembolism

Low molecular weight heparins as antineoplastic agents.

There is an increasing interest in the potential role of low molecular weight heparins (LMWHs) in the management of cancer patients. These antithrombotic agents have generated particular excitement because they have been proved useful in both the prevention and treatment of venous thromboembolism (VTE) in patients with malignancy. Recent reports are, at the same time, highlighting a potential role of LMWHs on patient survival due to their presumed antineoplastic action. This review will discuss the most recent reports and patents on these topics.

Italian survey on clinical practice in myeloproliferative neoplasms. A GIMEMA Myeloproliferative Neoplasms Working Party initiative

Superficial venous thrombosis: Prevalence of common genetic risk factors and their role on spreading to deep veins

Introduction. Superficial venous thrombosis (SVT) has been considered for a long time a limited clinical condition with a low importance, but this approach has changed in recent years, when several studies demonstrated spreading to deep veins occurring from 7.3 to 44%, with high prevalence of pulmonary embolism . Materials and Methods. To evaluate the prevalence of genetic risk factors for VTE in patients suffering from SVT on both normal and varicose vein, and to evaluate their role on spreading to deep veins, we studied 107 consecutive outpatients with symptomatic SVT. Ultrasound examination was performed, and the presence of FV Leiden, Prothrombin G20210A mutation, MTHFR C677T mutation w…

Recurrent venous thromboembolism complicated by heparin-induced thrombocytopenia as a first manifestation of an occult cancer: a case report.

Heparin-Induced Trombocytopenia (HIT) is a serious and potentially fatal complication of patients on heparins. Its management is difficult and it can be more complicated in patients with cancer because of the hemorrhagic risk carried out by direct inhibitor of thrombin, the currently approved drug for HIT. At present, it is not clear whether cancer patients also have an increased risk of HIT. We describe the case of a patient with occult cancer at the moment of the index venous thrombosis, who developed Deep Vein Thrombosis (DVT) and concomitant HIT with thrombotic complications (recurrent contralateral venous thrombosis). The management of HIT was efficaciously based on the combined use o…

Haemorheological profile in congenital afibrinogenemia and in congenital dysfibrinogenemia: A clinical case report

Although the inherited quantitative and qualitative disorders of fibrinogen are rare, in the course of time patients may develop complications including episodes of arterial and venous thrombosis. It can be useful to complete the laboratory assessment of these clinical conditions with the evaluation of the haemorheological profile. The data obtained from this study showed that congenital afibrinogenemia was characterized by a primary plasma hypoviscosity, whereas congenital dysfibrinogenemia by a primary plasma hyperviscosity. Both these haemorheological alterations may concur, with different mechanisms, to the pathogenesis of thrombotic vascular complications.

Transfusion Need at Diagnosis or Its Development During the First Year of Diagnosis in Primary Myelofibrosis: Effect On Survival and Correlation with JAK2 and TET2 Mutational Status.

Abstract Abstract 1909 Poster Board I-932 Background: The International Prognostic Scoring System (IPSS) for primary myelofibrosis (PMF) utilizes five independent predictors of inferior survival; of these, a hemoglobin level &lt;10 g/dL has the highest impact on survival (Cervantes et al. Blood 2009;113:2895). In the current study, we examined the additional prognostic impact of transfusion need at diagnosis or becoming transfusion-dependent in the first year of diagnosis. These events were also correlated with JAK2 or TET2 mutational status. Methods: Patients were selected from the Mayo Clinic PMF database based on availability of bone marrow histology and IPSS-relevant information at diag…

Italian Registry of Haemophilia and Allied Disorders. Objectives, methodology and data analysis

&lt;p&gt;Clinical Phenotype and Response to Different Lines of Therapy in Elderly with Immune Thrombocytopenia: A Retrospective Study&lt;/p&gt;

Purpose Insufficient knowledge of primary immune thrombocytopenia purpura (ITP) in the elderly, together with a lack of clinical trial data, has resulted in wide variation in treatments. Here, we present a study focused on clinical characteristics of ITP in older subjects at diagnosis integrated with the subsequent course of the disease and treatment history. Methods In a retrospective monoinstitutional study, we evaluated >65-year-old patients with primary ITP. Clinical characteristics at the time of diagnosis were described and analyzed. We aimed to delineate whether subsequent lines of therapy influenced the number of relapses. In addition to initial regimens, we reported subsequent trea…

Factor VII deficiency: evidence that in minor surgery one-day replacement therapy is sufficient

Ropeginterferon alfa-2b versus phlebotomy in low-risk patients with polycythaemia vera (Low-PV study): a multicentre, randomised phase 2 trial.

Summary Background There is no evidence that phlebotomy alone is sufficient to steadily maintain haematocrit on target level in low-risk patients with polycythaemia vera. This study aimed to compare the efficacy and safety of ropeginterferon alfa-2b on top of the standard phlebotomy regimen with phlebotomy alone. Methods In 2017, we launched the Low-PV study, a multicentre, open-label, two-arm, parallel-group, investigator-initiated, phase 2 randomised trial with a group-sequential adaptive design. The study involved 21 haematological centres across Italy. Participants were recruited in a consecutive order. Participants enrolled in the study were patients, aged 18–60 years, with a diagnosis…

Aspirin for preventing the recurrence of venous thromboembolism

The MASTER registry on venous thromboembolism: description of the study cohort.

Long-term risk for major bleeding during extended oral anticoagulant therapy for first unprovoked venous thromboembolism: A systematic review and meta-analysis

BACKGROUND The long-term risk for major bleeding in patients receiving extended (beyond the initial 3 to 6 months) anticoagulant therapy for a first unprovoked venous thromboembolism (VTE) is uncertain. PURPOSE To determine the incidence of major bleeding during extended anticoagulation of up to 5 years among patients with a first unprovoked VTE, overall, and in clinically important subgroups. DATA SOURCES MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception to 23 July 2021. STUDY SELECTION Randomized controlled trials (RCTs) and prospective cohort studies reporting major bleeding among patients with a first unprovoked VTE who were to receive oral anticoagu…

Oral vitamin K versus placebo to correct excessive anticoagulation in patients receiving warfarin: A randomized trial

BACKGROUND: Low-dose oral vitamin K decreases the international normalized ratio (INR) in overanticoagulated patients who receive warfarin therapy. Its effects on bleeding events are uncertain. OBJECTIVE: To see whether low-dose oral vitamin K reduces bleeding events over 90 days in patients with warfarin-associated coagulopathy. DESIGN: Multicenter, randomized, placebo-controlled trial. Randomization was computer-generated, and participants were allocated to trial groups by using sequentially numbered study drug containers. Patients, caregivers, and those who assessed outcomes were blinded to treatment assignment. SETTING: 14 anticoagulant therapy clinics in Canada, the United States, and …

Status of Recombinant Factor VIII Concentrate Treatment for Hemophilia A in Italy: Characteristics and Clinical Benefits

The current interest in recombinant factor VIII (rFVIII) products stems from the fact that they offer a technological solution to prolonging the half-life of and reducing the risk of formation of alloantibodies (inhibitors) against FVIII in treated patients with hemophilia A (HA). The Italian health care system has authorized the use of a wide range of rFVIII concentrates of the first, second, and third generation, as well as new innovative rFVIII preparates with an extended half-life (EHL) (Kogenate FS®-Bayer, belonging to the second generation and replaced since 2017 by a product consisting of the same modified molecule; because it is only available until the end of the current year, it w…

Managing cancer patients with acute venous thromboembolism: exploring safe alternatives to hospitalisation

Acute venous thromboembolism (VTE) is a common and potentially fatal complication that frequently occurs in cancer patients. Few data are currently available about the optimal management of this category of high-risk patients. In clinical practice, physicians have to deal with many problems related to cancer patients with acute VTE. For instance, cancer patients with deep vein thrombosis (DVT) are frequently admitted to the hospital since their high rate of recurrent thrombotic events and/or bleeding-related therapy; however, most of them would prefer alternatives to prolonged hospitalisation. Then, it is not clearly whether data coming from a non-cancer population (such as that regarding t…

Gastrointestinal bleeding in patients with von Willebrand disease; how long we can wait for surgery?

Evaluation of patients with thrombotic stroke by methionine loading oral curve

Catastrophic antiphospholipid syndrome in a patient with V Leiden variant

Prevalence and Prognostic Role of IDH Mutations in Acute Myeloid Leukemia: Results of the GIMEMA AML1516 Protocol

Simple Summary IDH1/2 mutations are a common event in acute myeloid leukemia (AML) and represent a therapeutic target. We designed the GIMEMA AML1516 observational protocol to examine the prevalence of IDH1/2 mutations and the associations between IDH mutations and clinico-biological parameters in a cohort of Italian patients affected by AML. By analyzing 284 consecutive adult AML patients, we confirmed that IDH1 and IDH2 mutations are frequently detected-14% and 18%, respectively-at diagnosis. IDH1/2 mutations were significantly associated with an inferior performance status and non-complex karyotype when compared to IDH1/2-WT. With regards to the outcome, in the subset of IDH1/2-mutated p…

Clinical course of patients with symptomatic isolated superficial vein thrombosis: the ICARO follow‐up study

Essentials Late sequelae of isolated superficial vein thrombosis (iSVT) have rarely been investigated. We studied 411 consecutive outpatients with acute iSVT with a median follow-up of three years. Male sex and cancer are risk factors for future deep vein thrombosis or pulmonary embolism. Patients without cancer appear to be at a negligible risk for death. SUMMARY Background Studies of long-term thromboembolic complications and death following acute isolated superficial vein thrombosis (iSVT) of the lower extremities are scarce. Objectives To investigate the course of iSVT in the setting of an observational multicenter study. Methods We collected longitudinal data of 411 consecutive outpati…

Optimizing tumor-reactive γδ T cells for antibody-based cancer immunotherapy.

Monoclonal antibodies (mAbs) constitute the most rapidly growing class of human therapeutics and the second largest class of drugs after vaccines. The treatment of B-cell malignancies and HER2/Neu(+) breast cancer has benefited considerably from the use of therapeutic mAbs, either alone or in combination with standard chemotherapy. Frequent relapses, however, demonstrate that the bioactivity of these mAbs is still suboptimal. The concept of improving the anti-tumor activity of mAbs is well established and potentiating the cytotoxicity induced by anticancer mAbs can be achieved by strategies that target the downstream cytolytic effector cells. The recruitment of Fcγ receptor-dependent functi…

Age at diagnosis is an important prognostic factor in Philadelphia-negative Myeloproliferative Neoplasms

A clinical score to rule out the concomitant presence of deep vein thrombosis in patients presenting with superficial vein thrombosis: The ICARO study

Superficial vein thrombosis (SVT) is commonly encountered in clinical practice. Recent studies have suggested that the concomitant presence of deep vein thrombosis (DVT) or pulmonary embolism (PE) at the time of SVT diagnosis is not uncommon, thus increasing the interest on this disease. Whether this coexistence is predicted by specific risk factors remains unknown.To evaluate potential risk factors for DVT coexistence in patients presenting with acute objectively diagnosed SVT of the lower limbs and to develop a simple score entirely based on clinical variables to define the pre-test probability of DVT in these patients.A multicenter, retrospective cohort study on SVT patients was conducte…

Il dosaggio dell'inibitore

TROMBOSI PROFONDA SUPERFICIALE ED ESTENSIONE AL CIRCOLO PROFONDO: RUOLO DEI FATTORI DI RISCHIO GENETICI

Prognostic relevance of an asymptomatic venous thromboembolism in patients with cance

Curva da carico orale di metionina nella valutazione di pazienti affetti da patologia trombotica

Cardiovascular Risk in Polycythemia Vera: Thrombotic Risk and Survival: Can Cytoreductive Therapy Be Useful in Patients with Low-Risk Polycythemia Vera with Cardiovascular Risk Factors?

&lt;b&gt;&lt;i&gt;Background/Aims:&lt;/i&gt;&lt;/b&gt; Cardiovascular risk factors are not considered in the current scores for evaluation of the thrombotic risk in myeloproliferative neoplasms, and in polycythemia vera (PV) in particular. Cytoreduction is currently not indicated in low-risk patients with PV, despite the absence or presence of cardiovascular risk factors. Our purpose is to highlight how cardiovascular risk factors in patients with PV increase the thrombotic risk both in low- and high-risk patients. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; We collected and analyzed data from 165 consecutive patients with a diagnosis of PV followed at our institution and compared the fr…

ISAM: international study on anticoagulation management. The Italian experience

Bone marrow characteristics predict outcome in a multicenter cohort of primary immune thrombocytopenia patients treated with thrombopoietin analogs

It is well established that immune thrombocytopenia (ITP) results from increased immune mediated platelet destruction (anti-platelets antibodies, autoreactive T cells, and reduction of regulatory T cells) along with impaired production in the bone marrow.1 The latter has been attributed to both cellular and humoral mediators that cause suppression of megakaryocyte production and maturation.2 Current standard first line therapy consists of corticosteroids, with or without intravenous Ig, achieving about 70-80% response rate. However, a consistent proportion of patients would relapse after corticosteroid discontinuation or tapering, and requires further therapy. ...

Absence of residual vein thrombosis after an episode of idiopatic deep vein thrombosis: short-term anticoagulation is safe. The extended DACUS Study

Abstract Background. The optimal duration of Oral Anticoagulant Therapy (OAT) for Deep Vein Thrombosis (DVT) can be tailored by Residual Vein Thrombosis (RVT) (Siragusa S et al. Blood2003;102(11):OC183), a marker able to assess the individual risk for recurrent thrombosis. However, in patients with idiopathic DVT the safety of early interruption of OAT, because of absence of RVT, is still debated. Objective of the study. In the present study, we evaluated the safety of withholding OAT, in patients with idiopathic DVT and without RVT, three months after the index thrombotic episode. Study design. Prospective controlled study with two groups: patients without RVT stopped OAT after 3 months wh…

Quality of Life in Patients With Cancer Under Prolonged Anticoagulation for High-Risk Deep Vein Thrombosis: a Long-Term Follow-Up

Current guidelines recommend to prolong anticoagulant treatment in patients with cancer with venous thromboembolism (VTE); only few studies evaluated other parameters than cancer itself for selecting patients at higher risk of recurrent VTE. Long-term management of VTE is thus challenged by several controversies mainly for patients compliance. We here report results of a long-term follow-up in patients with deep vein thrombosis under anticoagulant treatment with low-molecular-weight heparin (LMWH) for residual vein thrombosis (RVT) detected at compression ultrasonography (CUS), 6 months after standard anticoagulant treatment. Patients with RVT were deemed at high risk of recurrences and in…

Long-term death and recurrence in patients with acute venous thromboembolism: the MASTER registry

Mature Survival Data for 176 Patients Younger Than 60 Years With Primary Myelofibrosis Diagnosed Between 1976 and 2005: Evidence for Survival Gains in Recent Years

In the past 20 years, management of primary myelofibrosis (PMF) has incorporated new treatment approaches, but survival benefits have not been confirmed in controlled studies. This retrospective study includes 176 consecutive patients younger than age 60 years in whom PMF was diagnosed during a 30-year period (1976-2005). Median age at diagnosis was 50 years (range, 18-59 years), and 98 patients (55%) were men. At the time of this report, 99 patients (56%) had died; the 77 surviving patients were followed up for a median of 8 years (range, 4-24 years). Overall median survival was 9.2 years, and 15- and 20-year survival rates were 32% and 20%, respectively. According to the Dupriez Prognosti…

Asymptomatic Amyloidosis at the Time of Diagnostic Bone Marrow Biopsy in Newly Diagnosed Patients with Multiple Myeloma and Smoldering Multiple Myeloma.

Abstract Abstract 2803 Poster Board II-779 Background. The rate of asymptomatic amyloidosis (asym-amyloidosis) detected in patients with newly diagnosed multiple myeloma (MM) or smoldering multiple myeloma (SMM) is unknown. This topic is significant because unrecognized AL may be associated with increased mortality may change the patient's management. The objective of the present investigation was to evaluate the number and clinical significance of asym-amyloidosis in MM and SM patients at the time of the diagnostic bone marrow (BM) biopsy for MM. Materials and Methods. The study population was selected from the Mayo Clinic Dysproteinemia database and consisted of consecutive patients with …

CD200 ANTIGEN IN B-CELL DERIVED NEOPLASMS: EXPRESSION AND CLINICAL IMPACT IN 77 CONSECUTIVE PATIENTS OF A SINGLE ISTITUTION

Immune tolerance induction with moroctocog-alpha (Refacto/Refacto AF) in a population of Italian haemophilia A patients with high-titre inhibitors: Data from REF.IT Registry.

Background: The appearance of inhibitors is the most serious complication in haemophilia A (HA) patients. The primary objective is their eradication. Up to date, immune tolerance induction (ITI) was the only therapeutic option to achieve this. Aim: To assess the efficacy of moroctocog-alpha as an ITI regimen in a population of HA patients with high-titre inhibitors. Methods: The REF.IT Registry is a retrospective-prospective study that collected data on all patients with HA and high-titre inhibitors treated with moroctocog-alpha as an ITI regimen at twelve Italian Haemophilia Centres. Results: We enrolled 27 patients, 85.2% were children. All patients were high responders, 88.9% had severe …

Low dose of aPCC after the initial treatment in acquired haemophilia A is useful to reduce bleeding relapses: Data from the FAIR registry

Background: Bypassing agents are the first line therapy in patients with acquired haemophilia A (AHA). Activated prothrombin complex concentrate (aPCC) proved to be effective as initial treatment, but 20% of patients (pts) had relapses. aPCC as short-term prophylaxis to reduce subsequent bleeds is still not clear. Aim: To evaluate whether a short-term prophylaxis with low dose of aPCC can reduce bleeding relapses after initial AHA treatment, maintaining safety. Methods: The FAIR Registry is a retrospective-prospective study started on December 2012, that collected data on all pts with AHA treated with aPCC in 12 Italian Haemophilia Centers. All statistical analyses were carried out in the 5…

Clinical experience with optional vena cava filters: results of a prospective multicenter study

Natural History of Mesenteric Venous Thrombosis: A Large Multicentre Study

Abstract Introduction: Mesenteric venous thrombosis (MVT) is an uncommon but potentially life-threatening disease, accounting for 5–15% of mesenteric ischemic events. Most cases of MVT are either identified at laparotomy or at autopsy, with a mortality rate of approximately 50% in old series. Advances in imaging techniques have facilitated the early diagnosis of MVT and, thus, have contributed to a decrease in mortality in the more recent series. The treatment of MVT involves anticoagulation alone or in combination with surgery. Experts suggest that MVT can safely be managed without surgery if there is no evidence of bowel infarction. However, information on the natural history of MVT and o…

Peri-operative bridgning therapy with low molecular weight heparin in patients requiring interruption of long-term oral anticoagulant therapy

Post-transplant consolidation based on combination of lenalidomide and proteasome inhibitors in multiple myeloma

Multiple myeloma (MM) is a hematological malignancy due to uncontrolled proliferation of neoplastic plasma cells in the bone marrow, associated to chromosomal instability and cytogenetic abnormalities, which could have an impact on prognosis. Response to treatment and survival of newly diagnosed myeloma patients is heterogeneous, with median overall survival ranging from two to more than ten years, due to clinical and biological factors. To warrant long-term control of disease, several strategies have been proposed in the last years, including short-term high-dose of treatment, named as consolidation, before maintenance. This review will discuss the role of consolidation in the current myel…

ACP Journal Club. Warfarin thromboprophylaxis in cancer did not reduce risk for catheter-related thrombosis.

Host-related factors and cancer: Malnutrition and non-Hodgkin lymphoma

Assessment of host-related factors is a crucial aspect in the comprehensive management of cancer patients. A distinct nutritional disturbance linked to cancer has been recognized to be associated with negative outcomes. However, compared to solid tumors, only a limited number of studies have looked specifically at nutritional issues in the field of lymphoma. The aim of this review is to integrate the current knowledge on interactions between malnutrition and lymphoma and address most relevant and pertinent questions. We first provide a literature review on the mutual biological relationship between malnutrition and lymphoma. Next, we explore the overlap between malnutrition, sarcopenia, cac…

Clonal populations of hematopoietic cells with paroxysmal nocturnal hemoglobinuria phenotype in patients with splanchnic vein thrombosis

Abstract Introduction Splanchnic vein thrombosis (SVT) is a serious complication in patients with paroxysmal nocturnal hemoglobinuria (PNH). Mutant PNH clones can be associated with an increased risk of SVT even in the absence of overt disease, but their prevalence in non-selected SVT patients remains unknown. Materials and Methods Patients with objective diagnosis of SVT and without known PNH were tested for the presence of PNH clone using high-sensitivity flow cytometric analysis. Results A total of 202 SVT patients were eligible, 58.4% were males, mean age was 54.6 years (range 17–94), site of thrombosis was portal in 103 patients, mesenteric in 67, splenic in 37, and supra-hepatic in 10…

Immunoistochemical expression of PD-1 and PD-L1 in bone marrow biopsies of patients with acute myeloid leukemia

Background. Haematological and non-haematological malignancies are able to escape the host immune by the capacity to hijack the immune check-points. Several immune check-point molecules are known, such as T cell immunoglobulin mucin-3 (TIM-3), cytotoxic T-cell antigen-4 (CTLA-4), programmed death-1 (PD-1) with its ligand PD-L1 and others.1 The function of these immune check-points is to prevent the damage resulting from an excessive activation of the immune response in the setting of chronic antigenic stimulation, thus leading to autoimmune phenomena, as proved in knock-out mice models. PD-1 is normally present on activated T lymphocytes membrane, acting as a negative costimulatory receptor…

Incidence of venous thromboembolism in patients undergoing thoracotomy for lung cancer

Limited information exists on the incidence of symptomatic venous thromboembolism (vTE) in patients undergoing chest surgery for lung cancer. Several factors increase the thromboembolic risk in patients undergoing surgery for lung cancer: the intrinsic procoagulant effect of cancer,extensive surgical intervention, dependent limb position in the operating room, and vessel injury consequent to the operation. Furthermore,these patients might be especially vulnerable to pulmonary embolism (PE) because of the loss of lung tissue and the presence of chronic obstructive pulmonary disease and cardiovascular diseases caused by smoking.t Older studies found a very high incidence of thromboembolic eve…

Antimicorbial prophylaxis in patients with immune thrombocytopenia treated with rituximab:a retrospective analysis

PERIOPERATIVE BRIDGING THERAPY WITH LOW MOLECULAR WEIGH HEPARIN IN PATIENTS REQUIRING INTERRUPTION OF LONG-TERM ORAL ANTICOAGULANT THERAPY

Recombinant, activated factor VII for surgery in factor VII deficiency: a prospective evaluation - the surgical STER

Excessive bleeding represents a major complication of surgical interventions and its control is especially relevant in patients with Congenital Bleeding Disorders (CBD). In factor VII (FVII) deficiency, scanty data on surgery is available to guide treatment strategies. The STER (Seven Treatment Evaluation Registry) is a multi-centre, prospective, observational, web-based study protocol providing the frame for a structured and detailed data collection. Inhibitor occurrence was checked in a centralized fashion. Forty-one surgical operations (24 'major' and 17 'minor') were performed in 34 subjects with a carefully characterized FVII deficiency under the coverage of recombinant activated Facto…

Red blood cell deformability in multiple myeloma

The aim of this study was the evaluation of the erythrocyte deformability in multiple myeloma (MM). We enrolled 29MM patients and we evaluated, on fasting venous blood, the erythrocyte deformability, expressed as elongation index, and examined using the diffractometric method. By comparing normal controls and MM patients, a significant decrease in erythrocyte deformability, especially at low shear stresses, was found. In this research paper we evaluated all the hypothesis for a possible explanation of the behaviour of red blood cell deformability in MM, even considering how the alteration of erythrocyte deformability worsens the microcirculatory flow in these patients in association with th…

Prevention of venous thromboembolism in patients with cancer: guidelines of the Italian Society for Haemostasis and Thrombosis

MPL mutation effect on JAK2 46/1 haplotype frequency in JAK2V617F-negative myeloproliferative neoplasms

MPL mutation effect on JAK2 46/1 haplotype frequency in JAK2 V617F-negative myeloproliferative neoplasms

COVID-19 in Philadelphia-negative myeloproliferative disorders: a GIMEMA survey

PNEUMOCYSTIS JIROVECI PNEUMONIA IN HEMATOLOGICAL PATIENTS: A SINGLE INSTITUTION EXPERIENCE

Adherence to Treatment in Myelofibrosis Patients: Preliminary Results from Italian Romei Observational Study

Background: Non-adherence to medications is recognized as one of the most important and costly worldwide healthcare problems in the 21st century; according to an EU report, non-adherence to therapies is responsible for 194,500 deaths and costs €125 billion annually. Taking into account those data, the use of adherence measurements in clinical trials could be extremely useful, in order to better understand patients (pts) behaviours and outcomes. The 8-item Morisky Medication Adherence Scale (MMAS-8, Morisky DE et al, J Clin Hypertens,2008 - Krousel-Wood MA et al, Am J Manag Care 2009- Morisky DE et al, J Clin Epidemiol. 2011) is a widely used questionnaire to asses indirectly pts adherence t…

Acquired haemophilia in cancer: A systematic and critical literature review

Aim There is a paucity of data on the clinical presentation and management of cancer patients with acquired haemophilia (AH), we here report a systematic literature review on acquired haemophilia in the context of cancer. Methods Treatment outcomes of AH were defined as complete response (CR), partial response (PR) or no response (NR), based on inhibitor eradication, coagulation factor VIII levels and bleeding control. Reported deaths were either related to cancer or bleeding. Results Overall, 105 cases were collected and analyzed according to classification of cancer and efficacy of treatments for inhibitor and malignancy. The mean age was 68 years for both males (range 37-86 years) and fe…

Chromosome 1 abnormalities in myeloid malignancies: a literature survey and karyotype-phenotype associations.

Chromosome 1 is the largest human chromosome and contains over 1600 known genes and 1000 novel coding sequences or transcripts. It is, therefore, not surprising that recurrent chromosome 1 abnormalities are regularly encountered in both neoplastic and non-neoplastic medical conditions. The current review is focused on myeloid malignancies where we summarize the relevant published literature and discuss specific karyotype-phenotype associations. We show that chromosome 1 abnormalities are most frequent in BCR-ABL-negative classic myeloproliferative neoplasms (MPN): polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Specific abnormalities include duplicat…

Physicians' Perceptions of Clinical Utility of a Digital Health Tool for Electronic Patient-Reported Outcome Monitoring in Real-Life Hematology Practice. Evidence From the GIMEMA-ALLIANCE Platform

Digital health tools are increasingly being used in cancer care and may include electronic patient-reported outcome (ePRO) monitoring systems. We examined physicians’ perceptions of usability and clinical utility of a digital health tool (GIMEMA-ALLIANCE platform) for ePRO monitoring in the real-life practice of patients with hematologic malignancies. This tool allows for the collection and assessment of ePROs with real-time graphical presentation of results to medical staff. Based on a predefined algorithm, automated alerts are sent to medical staff. Participating hematologists completed an online survey on their experience with the platform. Of the 201 patients invited to participate betw…

The risk of cardiovascular events is reduced by lowering hyperhomocysteinemia short term B vitamins therapy

Peripheral circulating cells with paroxysmal nocturnal haemoglobinuria phenotype after a first episode of cerebral sinus vein thrombosis: Results from a multicentre cross-sectional study

Paroxysmal nocturnal haemoglobinuria (PNH) is a rare, potentially fatal disorder of haematopoietic stem cells caused by mutations in an X-linked gene called phosphatidylinositol glycan class A, characterised by intravascular haemolysis, bone marrow failure and thrombotic events. The disease can occur at any age, although preferentially it affects young adults; its estimated prevalence is about 1/500,000 [1]. Clinical symptoms are variable and can include haemolytic anaemia, moderate to severe impairment of haematopoiesis and, in approximately 40% of patients, thrombosis of the vessels of the abdomen, brain and skin [2]. Rare, atypical site thrombosis of the splanchnic veins or cerebral sinu…

Oral vitamin K effectively treats international normalised ratio (INR) values in excess of 10

SummaryUnanticipated elevation of the INR is common in patients receiving warfarin. We performed a prospective cohort study of 107 warfarintreated patients with INR values of more than 10 who received a single 2.5 mg dose of oral vitamin K. During the first week, one patient experienced major bleeding, and one died. In the first 90 days after enrolment four patients had major bleeding (3.7%, 1.0% to 9.3%), eight patients (7.5%, 3.3% to 14.2%) died and two had objectively confirmed thromboembolism. Based on our low rate of observed major bleeding we conclude that 2.5 mg of oral vitamin K is a reasonable treatment for patients with INR values of more than 10 who are not actively bleeding.

Clostridium difficile Induced Inflammasome Activation and Coagulation Derangements

C. difficile enterocolitis (CDAC) is the most common hospital infection, burdened by an increased incidence of coagulation-related complications such as deep vein thrombosis (DVT) and disseminated intravascular coagulation (DIC) as well as a significant sepsis-related mortality. In this review, we analyzed the available data concerning the correlation between coagulation complications related to C. difficile infection (CDI) and inflammasome activation, in particular the pyrin-dependent one. The little but solid available preclinical and clinical evidence shows that inflammasome activation increases the risk of venous thromboembolism (VTE). As proof of this, it has been observed that in vitr…

BCR-ABL1 Doubling-Times and Halving-Times May Predict CML Response to Tyrosine Kinase Inhibitors

In Chronic Myeloid Leukemia (CML), successful treatment requires accurate molecular monitoring to evaluate disease response and provide timely interventions for patients failing to achieve the desired outcomes. We wanted to determine whether measuring BCR-ABL1 mRNA doubling-times (DTs) could distinguish inconsequential rises in the oncogene’s expression from resistance to tyrosine kinase inhibitors (TKIs). Thus, we retrospectively examined BCR-ABL1 evolution in 305 chronic-phase CML patients receiving imatinib mesylate (IM) as a first line treatment. Patients were subdivided in two groups: those with a confirmed rise in BCR-ABL1 transcripts without MR3.0 loss and those failing IM. We found …

Management of Ponatinib in Patients with Chronic Myeloid Leukemia with Cardiovascular Risk Factors

Cardiovascular (CV) adverse events are considered common complications of ponatinib treatment. Recently, it has been demonstrated that ponatinib dose reductions in definite settings can obtain optimal responses and lower ponatinib-related CV events. In this study, we describe the management of 5 patients with chronic myeloid leukemia treated with ponatinib, from second to fourth line of tyrosine kinase inhibitor therapy, carrying high pre-ponatinib CV risk, who obtained optimal molecular response and developed no CV adverse event during follow-up. Among these 5 patients, 2 had diagnosis of ischemic heart disease and underwent percutaneous angioplasty, 2 had type 2 diabetes and arterial hype…

Survival in young patients with intermediate-/high-risk myelofibrosis: Estimates derived from databases for non transplant patients

Recent studies have suggested that allogenic stem cell transplantation (allo-SCT) might be a better treatment option, compared to drug therapy, for young patients with high-/intermediate-risk primary myelofibrosis (PMF). However, there are no controlled studies that validate this contention and allo-SCT is associated with a substantial risk of procedure-related mortality and morbidity. In a retrospective analysis of nontransplant PMF patients, who were both young (age <60 years) and with high-/intermediate-risk disease, 1- and 3-year survival estimates were 87% and 55%, 95% and 77%, 71% and 58%, respectively, involving patients seen at three different centers with expertise in PMF; these da…