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…

Increased risk for venous thrombosis in carriers of the prothrombin G→A20210 gene variant

A mutation in the prothrombin gene (G--A20210) has been associated with higher plasma prothrombin levels and an increased tendency for venous thrombosis.To determine whether the prothrombin A20210 allele is independently associated with the occurrence of venous thrombosis.Case-control study.Two thrombosis centers in southern Italy.281 consecutive patients with venous thrombosis confirmed by objective tests and 850 controls.Medical history was collected on standardized questionnaires. The presence of prothrombin G--A2020 and factor V Leiden mutations was determined by polymerase chain reaction. The presence of anticoagulant factors and prothrombin activity was determined by tests of function…

Prophylaxis In Congenital Factor VII Deficiency, Indications, Efficacy and Safety: Results of the STER

Abstract Abstract 665 Introduction Prophylaxis is considered a difficult endeavour in FVII deficiency, especially because of the very short FVII zymogen and FVIIa half-lives, mainly in childhood. The Seven Treatment Evaluation Registry (STER, www.targetseven.org) is a prospective observational, multi-centre, web-based registry concerned with the evaluation of treatments for spontaneous bleeding episodes, surgery and prophylaxis in patients with FVII deficiency. As regards prophylaxis, STER provides the frame for a structured and detailed data capture aiming at: a) identifying patients in whom prophylaxis is advisable, b) defining clinical settings in which prophylaxis is necessary and c) de…

Pathogen safety of long-term treatments for bleeding disorders: still relevant to current practice

Hemophilia defines a group of hereditary bleeding disorders: hemophilia A (deficiency of Factor VIII, FVIII), hemophilia B (deficiency of FIX), and para-hemophilia (deficiency of FV). These result from mutations in clotting factor genes. As in the large majority of bleeding disorders ([Table 1][1

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…

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…

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…

Factor V Leiden, C>T MTHFR Polymorphism and Genetic Susceptibility to Preeclampsia

SummaryWe performed a case-controlled study to investigate whether the FV Leiden mutation and the C>T677 polymorphism of the 5,10 methylene tetrahydrofolate reductase (MTHFR) are associated with the occurrence of preeclampsia in 96 otherwise healthy preeclamptic women and 129 parous women as controls. FV Leiden carriers were 10 (10.5%) in cases and 3 (2.3%) in controls (OR: 4.9, 95% Cl: 1.3-18.3). MTHFR TT homozygotes were 28 (29.8%) in cases and 24 (18.6%) in the control group (OR: 1.8,95% Cl 1.0-3.5). No difference in any of the polymorphisms was found between proteinuric (n = 45) and non-proteinur-ic (n = 51) patients. Moreover, MTHFR polymorphism does not affect the association betwe…

PAI-1 plasma levels in a general population without clinical evidence of atherosclerosis: relation to environmental and genetic determinants.

Abstract —Plasminogen activator inhibitor-1 (PAI-1) plasma levels have been consistently related to a polymorphism (4G/5G) of the PAI-1 gene. The renin-angiotensin pathway plays a role in the regulation of PAI-1 plasma levels. An insertion ( I )/deletion ( D ) polymorphism of the angiotensin-converting enzyme (ACE) gene has been related to plasma and cellular ACE levels. In 1032 employees (446 men and 586 women; 22 to 66 years old) of a hospital in southern Italy, we investigated the association between PAI-1 4G/5G and the ACE I/D gene variants and plasma PAI-1 antigen levels. None of the individuals enrolled had clinical evidence of atherosclerosis. In univariate analysis, PAI-1 levels we…

Cardiovascular risk factors, angiotensin-converting enzyme gene I/D polymorphism, and left ventricular mass in systemic hypertension.

We investigated the influence of major cardiovascular risk factors (smoking, hypercholesterolemia, diabetes mellitus) on the association between angiotensin-converting enzyme (ACE) gene insertion (I)/deletion (D) polymorphism and echocardiographic left ventricular mass in 225 patients with sustained hypertension, assessed by ambulatory blood pressure monitoring. When the study population was analyzed as a whole, the 3 ACE genotypes did not differ in left ventricular mass (II, 47 g/m2.7; ID, 49 g/m2.7; DD, 51 g/m2.7; p = NS). No difference was found in subjects (n = 135) in whom at least 1 major cardiovascular risk factor was present (II, 51 g/m2.7; ID, 51 g/m2.7; DD: 52 g/m2.7; p = NS). In …

Prophylaxis in congenital factor VII deficiency: indications, efficacy and safety. Results from the Seven Treatment Evaluation Registry (STER)

WOS: 000319897700018

Comparison of the rates of joint arthroplasty in patients with severe factor VIII and IX deficiency: an index of different clinical severity of the 2 coagulation disorders

AbstractData from the Italian Hemophilia Centres were collected to perform a retrospective survey of joint arthroplasty in patients with severe hemophilia. Twenty-nine of 49 hemophilia centers reported that 328 of the 347 operations were carried out in 253 patients with severe hemophilia A (HA) and 19 in 15 patients with severe hemophilia B (HB). When results were normalized to the whole Italian hemophilia population (1770 severe HA and 319 severe HB), patients with HA had a 3-fold higher risk of undergoing joint arthroplasty (odds ratio [OR], 3.38; 95% confidence interval [CI], 1.97-5.77; P < .001). These results were confirmed after adjustment for age, HIV, hepatitis C virus (HCV), and…

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 <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…

Acquired inhibitors of clotting factors: AICE recommendations for diagnosis and management

Appropriateness of oral anticoagulant therapy prescription and its associated factors in hospitalized older people with atrial fibrillation

Aims: Although oral anticoagulants (OACs) are effective in preventing stroke in older people with atrial fibrillation (AF), they are often underused in this particularly high-risk population. The aim of the present study was to assess the appropriateness of OAC prescription and its associated factors in hospitalized patients aged 65 years or older. Methods: Data were obtained from the retrospective phase of Simulation-based Technologies to Improve the Appropriate Use of Oral Anticoagulants in Hospitalized Elderly Patients With Atrial Fibrillation (SIM-AF) study, held in 32 Italian internal medicine and geriatric wards. The appropriateness of OAC prescription was assessed, grouping patients …

Extended use of dabigatran, warfarin, or placebo in venous thromboembolism

International audience; BACKGROUND: Dabigatran, which is administered in a fixed dose and does not require laboratory monitoring, may be suitable for extended treatment of venous thromboembolism. METHODS: In two double-blind, randomized trials, we compared dabigatran at a dose of 150 mg twice daily with warfarin (active-control study) or with placebo (placebo-control study) in patients with venous thromboembolism who had completed at least 3 initial months of therapy. RESULTS: In the active-control study, recurrent venous thromboembolism occurred in 26 of 1430 patients in the dabigatran group (1.8%) and 18 of 1426 patients in the warfarin group (1.3%) (hazard ratio with dabigatran, 1.44; 95…

Inherited Thrombophilic Risk Factors and Venous Thromboembolism

Study objectives To investigate whether the FIIA20210 mutation is associated with isolated pulmonaryembolism (PE). Design Case-control study. Setting Five thrombosis centers in southern Italy. Patients Six hundred forty-seven consecutive referredpatients with objectively documented venous thrombosis and 1,329control subjects. Measurements and results Medicalhistories were collected. The G-to-A transition at nucleotide 1691within the factor V gene (FV Leiden) and the G-to-A transition atnucleotide position 20210 within the prothrombin gene locus (FIIA20210), levels of anticoagulant factors, and levelsof antiphospholipid antibodies were determined by standard techniques.Patients with deep ven…

Pain assessment and management in Italian Haemophilia Centres

BACKGROUND: Although the widespread use of factor VIII/IX replacement therapy has significantly reduced the severity of arthropathy in persons with haemophilia (PWH), some develop degenerative joint changes, associated with significant pain. The aim of this survey was to investigate the management and perception of pain among Italian physicians who treat PWH. MATERIALS AND METHODS: Between September and October 2017, a questionnaire was distributed to 35 Italian haemophilia treatment centres (60 physicians). RESULTS: Fifty-three haemophilia specialists completed the survey. We found that there was good agreement (98.1%) on the need to investigate pain at each clinical visit, but there was h…

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…

Identifying human platelet glycoproteins IIb and IIIa by capillary electrophoresis.

Glanzmann thrombasthenia (GT) is an inherited hemorrhagic defect due to a failure of the platelet membrane glycoprotein (GP) IIb–IIIa complex. Capillary electrophoresis (CE) analysis of solubilized platelet membranes from normal individuals showed the presence of two peaks with a migration time of 27 and 29 min, respectively. An excellent run-to-run and day-to-day reproducibility of the technique (< 1% variation of the retention time) was documented. Using an automated Ferguson method, the apparent molecular masses were 100.0 kDa and 138.5 kDa, respectively. Immunoprecipitation with monoclonal antibodies anti-GP IIIa (B59.2.1) and anti-IIb (61.9.1.3) showed the two peaks as IIIa and IIb, re…

Hemostatic balance in patients with liver cirrhosis: Report of a consensus conference.

Abstract Patients with cirrhosis present with hemostatic alterations secondary to reduced availability of pro-coagulant and anti-coagulant factors. The net effect of these changes is a rebalanced hemostatic system. The Italian Association of the Study of the Liver (AISF) and the Italian Society of Internal Medicine (SIMI) promoted a consensus conference on the hemostatic balance in patients with cirrhosis. The consensus process started with the review of the literature by a scientific board of experts and ended with a formal consensus meeting in Rome in December 2014. The statements were graded according to quality of evidence and strength of recommendations, and approved by an independent …

Appropriateness of oral anticoagulant therapy prescription and its associated factors in hospitalized older people with atrial fibrillation

Aims Although oral anticoagulants (OACs) are effective in preventing stroke in older people with atrial fibrillation (AF), they are often underused in this particularly high-risk population. The aim of the present study was to assess the appropriateness of OAC prescription and its associated factors in hospitalized patients aged 65 years or older. Methods Data were obtained from the retrospective phase of Simulation-based Technologies to Improve the Appropriate Use of Oral Anticoagulants in Hospitalized Elderly Patients With Atrial Fibrillation (SIM-AF) study, held in 32 Italian internal medicine and geriatric wards. The appropriateness of OAC prescription was assessed, grouping patients in…