In-hospital outcomes of catheter-directed thrombolysis in patients with pulmonary embolism.

AbstractAimsCatheter-directed treatment of acute pulmonary embolism (PE) is technically advancing. Recent guidelines acknowledge this treatment option for patients with overt or imminent haemodynamic decompensation, particularly when systemic thrombolysis is contraindicated. We investigated patients with PE who underwent catheter-directed thrombolysis (CDT) in the German nationwide inpatient cohort.Methods and resultsData from hospitalizations with PE (International Classification of Disease code I26) between 2005 and 2016 were collected by the Federal Office of Statistics in Germany. Patients with PE who underwent CDT (OPS 8-838.60 or OPS code 8-83b.j) were compared with patients receiving…

Home treatment of patients with low-risk pulmonary embolism with the oral factor Xa inhibitor rivaroxaban: Rationale and design of the HoT-PE Trial

SummaryPulmonary embolism (PE) is a potentially life-threatening acute cardiovascular syndrome. However, more than 95 % of patients are haemodynamically stable at presentation, and among them are patients at truly low risk who may qualify for immediate or early discharge. The Home Treatment of Pulmonary Embolism (HoT-PE) study is a prospective international multicentre single-arm phase 4 management (cohort) trial aiming to determine whether home treatment of acute lowrisk PE with the oral factor Xa inhibitor rivaroxaban is feasible, effective, and safe. Patients with confirmed PE, who have no right ventricular dysfunction or free floating thrombi in the right atrium or ventricle, are eligib…

Venous thromboembolism in patients hospitalized for hip joint replacement surgery

Venous thromboembolism (VTE) is a potentially life-threatening disease. Major transient risk factors include trauma, surgery, and immobilization. Patients undergoing hip joint replacement (HJR) are characterized by a high risk of postoperative VTE, but data on the time trends of VTE rates in this population are sparse.In an analysis of the German nationwide inpatient sample, we included all hospitalizations for elective primary HJR in Germany from 2005 to 2016. Time trends of the surgical procedure, overall death rates, and VTE rates were analysed, and predictors of VTE identified.Overall, 1,885,839 inpatients with elective primary HJR (59.1% women, 51.4% ≥70 years) were included in the ana…

Sex-specific differences in the presentation, clinical course, and quality of life of patients with acute venous thromboembolism according to baseline risk factors. Insights from the PREFER in VTE

Abstract Introduction Sex and the presence of specific provoking risk factors, along with age, influence the presentation and prognosis of venous thromboembolism (VTE). We investigated the presentation, course and quality of life in women and men with acute VTE classified according to their VTE provoking factors. Methods PREFER in VTE is an international, non-interventional registry of patients with a first episode of acute symptomatic VTE. Baseline provoking factors were classified as follows: major transient, minor transient, active cancer, and none identifiable. The primary outcome was recurrent VTE. Quality of life and treatment satisfaction were secondary outcomes. Results Of 3,455 pat…

Management of high-risk pulmonary embolism in an "unstable medical environment": Not only a matter of hemodynamic.

Safety of prothrombin complex concentrate in healthy subjects

Keywords: anticoagulants; prothrombin complex concentrate; thrombosis; reversal; meta-analysis; bleeding disorders

Incidence of symptomatic venous thromboembolism following hospitalization for coronavirus disease 2019: Prospective results from a multi-center study

Background Thrombosis and pulmonary embolism appear to be major causes of mortality in hospitalized coronavirus disease 2019 (COVID-19) patients. However, few studies have focused on the incidence of venous thromboembolism (VTE) after hospitalization for COVID-19. Methods In this multi-center study, we followed 1529 COVID-19 patients for at least 45 days after hospital discharge, who underwent routine telephone follow-up. In case of signs or symptoms of pulmonary embolism (PE) or deep vein thrombosis (DVT), they were invited for an in-hospital visit with a pulmonologist. The primary outcome was symptomatic VTE within 45 days of hospital discharge. Results Of 1529 COVID-19 patients discharge…

Lemierre syndrome: Current evidence and rationale of the Bacteria-Associated Thrombosis, Thrombophlebitis and LEmierre syndrome (BATTLE) registry.

Abstract Lemierre syndrome is a rare but potentially fatal condition characterized by septic thrombophlebitis of the head and neck district, preferentially affecting adolescents and young adults and manifesting as a complication of a local bacterial infection – typically, a pharyngotonsillitis or an abscess. It is historically associated with the Gram-negative anaerobic rod Fusobacterium necrophorum and with thrombophlebitis of the internal jugular vein. However, its definition has never been firmly established, and its spectrum within the continuum of bacteria-associated thrombophlebitis may be larger than what presumed so far. Recent evidence suggests that its prognosis remains serious ev…

Lemierre Syndrome: Clinical Update and Protocol for a Systematic Review and Individual Patient Data Meta-analysis.

Lemierre syndrome usually affects otherwise healthy adolescents or young adults and occurs at an overall rate of 1 to 10 cases per million person-years with an estimated fatality rate of 4 to 9%. Diagnostic criteria remain debated and include acute neck/head bacterial infection (often tonsillitis caused by anaerobes at high potential for sepsis and vascular invasion, notably Fusobacterium necrophorum) complicated by local vein thrombosis, usually involving the internal jugular vein, and systemic septic embolism. Medical treatment is based on antibiotic therapy with anaerobic coverage, anticoagulant drugs and supportive care in case of sepsis. Surgical procedures can be required, including d…

Antithrombotics and new interventions for venous thromboembolism: Exploring possibilities beyond factor IIa and factor Xa inhibition.

Abstract Direct oral anti–activated factor X and antithrombin agents have largely replaced vitamin K antagonists as the standard of care in treatment of venous thromboembolism. However, gaps in efficacy and safety persist, notably in end‐stage renal disease, implantable heart valves or assist devices, extracorporeal support of the circulation, and antiphospholipid syndrome. Inhibition of coagulation factor XI (FXI) emerges as a promising new therapeutic target. Antisense oligonucleotides offer potential advantages as a prophylactic or therapeutic modality, with one dose‐finding trial in orthopedic surgery already published. In addition, monoclonal antibodies blocking activation and/or activ…

Survival and recurrent venous thromboembolism in patients with first proximal or isolated distal deep vein thrombosis and no pulmonary embolism

Essentials The long-term risk of recurrence and death after distal deep vein thrombosis (DVT) is uncertain. We included subjects with first proximal or isolated distal DVT (IDDVT) and no pulmonary embolism. The risk of symptomatic and asymptomatic recurrence is lower after IDDVT (vs. proximal). IDDVT may be associated with a lower long-term risk of death, especially after unprovoked DVT. SummaryBackground A few studies have focused on the risk of recurrence after first acute isolated distal deep vein thrombosis (IDDVT) compared with proximal DVT (PDVT), whereas the incremental risk of death has never been explored beyond the first 3 years after acute event. Methods Our single-center cohort …

c.451dupT in KLKB1 is common in Nigerians, confirming a higher prevalence of severe prekallikrein deficiency in Africans compared to Europeans

Essentials Prekallikrein (PK) deficiency is a recessive trait with isolated aPTT prolongation. KLKB1 c.451dupT is common in Nigerians (7/600 alleles) and absent in a European group (0/600). To date, all genotyped PK-deficient patients of African ancestry were homozygous for 451dupT. Diagnostics of isolated aPTT prolongation in African descendants should include PK testing. ABSTRACT: Background Severe prekallikrein deficiency (PK deficiency) is an autosomal-recessive condition thought to be very rare. Recently we reported that the previously unnoticed variant c.451dupT, p.Ser151Phefs*34 in KLKB1, which is listed in databases aggregating genome data, causes PK deficiency and is common in Afri…

The Millennial Generation of Thrombosis and Hemostasis

Course of D-Dimer and C-Reactive Protein Levels in Survivors and Nonsurvivors with COVID-19 Pneumonia: A Retrospective Analysis of 577 Patients

Ambulatory treatment of low-risk pulmonary embolism in fragile patients: a subgroup analysis of the multinational Home Treatment of Pulmonary Embolism (HoT-PE) Trial

Pulmonary embolism is the third most frequent acute cardiovascular disease with an annual incidence of approximately 100 cases per 100 000 population and an annual mortality of ≥7 deaths per 100 000 population in the European region [1, 2]. Initial management is adjusted to the risk of in-hospital death or early complications, which depend both on the severity of pulmonary embolism and the presence of comorbidities [3]. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors hav…

In-hospital outcomes of catheter-directed thrombolysis in patients with pulmonary embolism

Abstract Background and purpose Catheter-directed treatment of acute pulmonary embolism (PE) is technically advancing. Recent guidelines acknowledge this treatment option for patients with overt or imminent haemodynamic decompensation, particularly when systemic thrombolysis is contraindicated or has failed. We investigated baseline characteristics and in-hospital outcomes of patients with PE who underwent catheter-directed thrombolysis (CDT) in the German nationwide inpatient cohort. Methods Data from hospitalizations with PE between 2005 and 2016 were collected by the Federal Office of Statistics (Statistisches Bundesamt) in Germany and included in this analysis. Patients with PE who unde…

Clinical course of isolated distal deep vein thrombosis in patients with active cancer: a multicenter cohort study

Essentials Isolated distal deep vein thrombosis (IDDVT) is frequently associated with cancer. No study has specifically evaluated the long-term clinical course of cancer-associated IDDVT. Patients with cancer-associated IDDVT are at very high risk of symptomatic recurrence and death. We observed low rates of major bleeding during anticoagulation. SummaryBackground Although isolated distal deep vein thrombosis (IDDVT) is frequently associated with cancer, no study has specifically evaluated the long-term clinical course of IDDVT in this setting. Aim To provide data on the rate of recurrent venous thromboembolism (VTE), major bleeding events and death in IDDVT patients with active cancer. Pat…

Venous thromboembolism in patients hospitalized for knee and hip joint replacement surgery

Abstract Background Venous thromboembolism (VTE) is a frequent acute cardiovascular disease, leading to significant morbidity and mortality worldwide. Major trauma, surgery, immobilisation and joint replacements are major provoking factors for VTE. In particular, patients undergoing knee and hip joint replacement surgery are at high risk of developing VTE perioperatively, even in the era of established pharmacological thromboprophylaxis. Without thromboprophylaxis, as many as 20–60% of patients may develop perioperative VTE. Purpose As recent studies indicate an increasing number of total knee and hip replacement surgeries in European countries and the United States, aims of our study were …

P5017Factors associated with a negative D-dimer test in patients diagnosed with acute symptomatic pulmonary embolism

Abstract Background The recommended diagnostic strategy for suspected acute pulmonary embolism (PE) combines the assessment of pre-test probability, D-dimer level, and -if indicated- computed tomography pulmonary angiography. Purpose To evaluate the frequency and potential explanations for negative D-dimer tests in patients diagnosed with acute PE. Methods The multicentre Follow-up of Acute Pulmonary Embolism (FOCUS) cohort study prospectively enrolled 1,100 consecutive patients diagnosed with acute symptomatic PE; two-year follow-up is ongoing. The items of the Simplified revised Geneva Score and the D-dimer levels at diagnosis have been prospectively collected, but they did not necessaril…

Severe High Molecular Weight Kininogen (HK) Deficiency: Clinical Characteristics, Deficiency-Causing KNG1 Variants in Reported and New Cases, and Estimated Prevalence

Abstract Background: Severe high molecular weight kininogen (HK) deficiency is an autosomal recessive defect of the contact system caused by mutations in KNG1. Limited scientific interest in HK deficiency due to the rarity of the seemingly asymptomatic condition may increase, as HK, the precursor of bradykinin, is now discussed as a therapeutic target e.g. in hereditary angioedema. Aims: We provide a comprehensive analysis of the diagnostic, clinical, and genetic features of HK deficiency and estimate its frequency. Methods: We identified a new case of HK deficiency, systematically review the literature, conduct new genetic studies of reported cases, and comprehensively analyze the clinical…

A model for estimating the health economic impact of earlier diagnosis of chronic thromboembolic pulmonary hypertension

Background Diagnostic delay of chronic thromboembolic pulmonary hypertension (CTEPH) exceeds 1 year, contributing to higher mortality. Health economic consequences of late CTEPH diagnosis are unknown. We aimed to develop a model for quantifying the impact of diagnosing CTEPH earlier on survival, quality-adjusted life-years (QALYs) and healthcare costs. Material and methods A Markov model was developed to estimate lifelong outcomes, depending on the degree of delay. Data on survival and quality of life were obtained from published literature. Hospital costs were assessed from patient records (n=498) at the Amsterdam UMC – VUmc, which is a Dutch CTEPH referral center. Medication costs were ba…

Reperfusion treatment for high-risk pulmonary embolism associated with COVID-19

Severe plasma prekallikrein deficiency : clinical characteristics, novel KLKB1 mutations, and estimated prevalence

BACKGROUND Severe plasma prekallikrein (PK) deficiency is an autosomal-recessive defect characterized by isolated activated partial thromboplastin time prolongation. To date, no comprehensive methodologically firm analysis has investigated the diagnostic, clinical, and genetic characteristics of PK deficiency, and its prevalence remains unknown. PATIENTS/METHODS We described new families with PK deficiency, retrieved clinical and laboratory information of cases systematically searched in the (gray) literature, and collected blood of these cases for complementary analyses. The Genome Aggregation Database (gnomAD) and the population-based Gutenberg Health Study served to study the prevalence …

Home treatment of fragile patients with acute pulmonary embolism: a subgroup analysis of the multinational home treatment of pulmonary embolism (HoT-PE) trial

Abstract Background and aims Subgroup analyses of randomized trials and cohort studies on direct oral anticoagulants (DOACs) suggested that single direct drug treatment may be effective and safe in elderly and “fragile” patients with acute pulmonary embolism (PE). In a post-hoc analysis of HoT-PE, a prospective multicenter management trial, we studied whether early discharge and home treatment of acute PE is effective and safe in these patients. Methods HoT-PE enrolled patients with acute PE classified as being at low risk based on the modified Hestia criteria and the absence of right ventricular dysfunction. The primary efficacy outcome was symptomatic recurrent VTE, or PE-related death wi…

The Post-COVID-19 Functional Status scale: a tool to measure functional status over time after COVID-19

Since the outbreak of the Coronavirus disease 2019 (COVID-19) pandemic, most attention has focused on containing transmission of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and addressing the surge of critically ill patients in acute care settings. Indeed, as of April 29th 2020, over 3 million confirmed cases have been accounted for globally [1]. In the coming weeks and months, emphasis will gradually involve also post-acute care of COVID-19 survivors. It is anticipated that COVID-19 may have a major impact on physical, cognitive, mental and social health status, also in patients with mild disease presentation [2]. Previous outbreaks of coronaviruses have been associate…

Residual vein obstruction in patients diagnosed with acute isolated distal deep vein thrombosis associated with active cancer.

After acute proximal deep vein thrombosis (DVT) the thrombotic mass decreases, especially during the first months of anticoagulation. The persistence of residual vein obstruction (RVO) may predict future recurrence in patients with cancer-associated DVT. We aimed to evaluate the proportion of patients with RVO after an episode of cancer associated isolated distal DVT (IDDVT), to identify variables associated with RVO, and to provide initial evidence of its association with recurrent VTE. We performed a post-hoc analysis of a multicenter cohort study of patients with isolated cancer-associated acute IDDVT. We included patients who underwent a control ultrasonography at the end of the anticoa…

COVID-19 in thrombosis research: An editorial perspective

Survival and quality of life after early discharge in low-risk pulmonary embolism.

IntroductionEarly discharge of patients with acute low-risk pulmonary embolism requires validation by prospective trials with clinical and quality-of-life outcomes.MethodsThe multinational Home Treatment of Patients with Low-Risk Pulmonary Embolism with the Oral Factor Xa Inhibitor Rivaroxaban (HoT-PE) single-arm management trial investigated early discharge followed by ambulatory treatment with rivaroxaban. The study was stopped for efficacy after the positive results of the predefined interim analysis at 50% of the planned population. The present analysis includes the entire trial population (576 patients). In addition to 3-month recurrence (primary outcome) and 1-year overall mortality, …

Quality of Life 3 and 12 Months Following Acute Pulmonary Embolism

BACKGROUND Few data are available on the long-term course and predictors of quality of life (QoL) following acute pulmonary embolism (PE). RESEARCH QUESTION What are the kinetics and determinants of disease-specific and generic health-related QoL 3 and 12 months following an acute PE? STUDY DESIGN AND METHODS The Follow-up after Acute Pulmonary Embolism (FOCUS) study prospectively followed up consecutive adult patients with objectively diagnosed PE. Patients were considered for study who completed the Pulmonary Embolism Quality of Life (PEmb-QoL) questionnaire at predefined visits 3 and 12 months following PE. The course of disease-specific QoL as assessed using the PEmb-QoL and the impact …

P2772The rule-out criteria for chronic thromboembolic pulmonary hypertension can identify patients without haemodynamic abnormalities and functional limitation 3 and 12 months after acute PE

Abstract Background Up to one-third of patients report persisting hemodynamic abnormalities and functional limitation over long-term follow-up after acute pulmonary embolism (PE). Purpose We tested whether a validated algorithm designed to rule-out chronic thromboembolic pulmonary hypertension (CTEPH) after acute PE can be used for identifying patients at lower risk of presenting with persisting symptoms and echocardiographic abnormalities. Methods The multicentre Follow-up of Acute Pulmonary Embolism (FOCUS) cohort study prospectively enrolled 1,100 consecutive patients diagnosed with acute symptomatic PE; two-year follow-up is ongoing. We focused on the scheduled visits for 3- and 12-mont…

Anti-Factor Xa levels correlate with recurrent venous thromboembolism and clinically relevant bleeding in patients receiving low-molecular-weight heparin

Background: The aim of our study was to investigate whether anti-Xa levels assessed in selected groups of LMWH-treated patients with VTE correlate with the risk of developing thromboembolic or bleeding complications. Methods: Retrospective study, in adult patients treated with anti-Xa-adjusted LMWH analysing the association between anti-Xa activity and recurrent VTE or bleeding. Primary outcomes were symptomatic fatal or nonfatal objectively diagnosed VTE and clinically relevant bleeding (ISTH criteria). Results: From 2007-2017, 192 patients were recruited. Mean age was 62 (SD 18) years and 48% were men. Indications for anti-Xa monitoring were: VTE recurrence under anticoagulation (20.8%), …

OC-01 - Clinical history of cancer patients with isolated distal deep vein thrombosis: a multicenter cohort study

Introduction Isolated distal deep vein thrombosis (IDDVT) accounts for one-fourth to one-half of all deep vein thrombosis (DVT) of the leg. Patients with IDDVT are frequently treated for a shorter period of time compared to patients with proximal DVT and/or pulmonary embolism (PE) due to a perceived lower risk of recurrence. About 10-20% of patients with venous thromboembolic events (VTEs) have concomitant cancer. Guidelines recommend long-term anticoagulant treatment in this group of patients due to their high risk of VTE recurrence. Unfortunately, information on the clinical history of IDDVT patients is limited and, to date, no study has evaluated the long-term risk of VTE recurrence in I…

Early switch to oral anticoagulation in patients with acute intermediate-risk pulmonary embolism (PEITHO-2) : a multinational, multicentre, single-arm, phase 4 trial

BACKGROUND: Current guidelines recommend a risk-adjusted treatment strategy for the management of acute pulmonary embolism. This is a particular patient category for whom optimal treatment (anticoagulant treatment, reperfusion strategies, and duration of hospitalisation) is currently unknown. We investigated whether treatment of acute intermediate-risk pulmonary embolism with parenteral anticoagulation for a short period of 72 h, followed by a switch to a direct oral anticoagulant (dabigatran), is effective and safe. METHODS: We did a multinational, multicentre, single-arm, phase 4 trial at 42 hospitals in Austria, Belgium, France, Germany, Italy, Netherlands, Romania, Slovenia, and Spain. …

P2540Sex-specific differences in the clinical presentation, surgical complications, and course of chronic thromboembolic pulmonary hypertension

Abstract Background Women are more susceptible to develop several forms of pulmonary hypertension, but they may have better survival rates than men. Sparse data are available concerning sex-specific differences in chronic thromboembolic pulmonary hypertension (CTEPH). Purpose and methods We investigated sex-specific differences in the clinical presentation of CTEPH, functional parameters, exposure to pulmonary endarterectomy (PEA), and survival. Results Women constituted half of the study population (N=679 treatment-naïve patients from the European CTEPH registry) and were characterized by a lower prevalence of some cardiovascular risk factors (e.g. prior acute coronary syndrome, smoking ha…

Home parenteral nutrition-associated thromboembolic and bleeding events: results of a cohort study of 236 individuals

UNLABELLED Essentials Sparse or outdated studies focus on thrombotic and bleeding risk in home parenteral nutrition (HPN). 236 HPN patients followed at a single center for a total of 684 patient-years were evaluated. Rates of venous thrombosis and major bleeding, and prevalence of vena cava syndrome are provided. Anticoagulants might reduce thrombosis risk, but population-specific safety concerns remain. SUMMARY Background Home parenteral nutrition (HPN) is necessary for patients with intestinal failure. Recurrent catheter-related thrombosis (CRT) is common, leading to infectious complications, pulmonary embolism, vascular access loss and intestinal transplantation. The efficacy and safety …

Compromised Lung Volume and Hemostatic Abnormalities in COVID-19 Pneumonia: Results from an Observational Study on 510 Consecutive Patients

Background: Hemostatic abnormalities have been described in COVID-19, and pulmonary microthrombosis was consistently found at autopsy with concomitant severe lung damage. Methods: This is a retrospective observational cross-sectional study including consecutive patients with COVID-19 pneumonia who underwent unenhanced chest CT upon admittance at the emergency room (ER) in one large academic hospital. QCT was used for the calculation of compromised lung volume (%CL). Clinical data were retrieved from patients’ files. Laboratory data were obtained upon presentation at the ER. Aim: The aim of this study was to evaluate the correlation between hemostatic abnormalities and lung involvement in pa…

Thrombosis and thromboembolism related to COVID‐19: A clarion call for obtaining solid estimates from large‐scale multicenter data

Abstract The clinical spectrum of coronavirus disease 2019 (COVID‐19) is wide, ranging from minor, nonspecific symptoms to severe pneumonia, acute respiratory distress syndrome, multiorgan involvement, and shock. In severe cases, the acute systemic inflammatory response, coagulation activation, and diffuse endothelial damage may, in combination with hypoxia, immobilization, and underlying risk factors, result in potentially life‐threatening venous and arterial thrombotic events. The first data from single‐center retrospective studies suggest that thrombotic events are a key aspect of COVID‐19‐associated morbidity and mortality. We have planned and will be launching the COvid REgistry on THR…

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…

Prevalence of pulmonary embolism in 127 945 autopsies performed in cancer patients in the United States between 2003 and 2019

Abstract Background Pulmonary embolism (PE) is a potentially fatal disease, but data on the incidence of fatal PE in cancer patients are scant. Objective We sought to estimate the proportion of cancer patients with PE at autopsy. Methods For this retrospective cohort study, all autopsy reports of cancer patients were retrieved from PALGA: Dutch Pathology Registry and used for data extraction. The primary outcome was PE at time of autopsy, defined as any clot obstructing a pulmonary artery. The secondary outcome was venous thromboembolism, defined as the composite of thrombotic PE, deep vein thrombosis, splanchnic vein thrombosis, or internal jugular vein thrombosis. Results A total of 9571 …

Detection and Differential Diagnosis of Prekallikrein Deficiency: Genetic Study of New Families and Systematic Review of the Literature

Abstract Introduction. Prekallikrein (PK) and high-molecular-weight kininogen (HK) deficiencies are ultra-rare, autosomal-recessive defects of the contact system caused by biallelic mutations in the KLKB1 and KNG1 genes, respectively. Since affected subjects do not manifest a bleeding phenotype, a correct diagnosis is essential to prevent the administration of prohemostatic agents or plasma and to avoid delay of surgery. We describe a new case of PK deficiency identified at UMC Mainz. In addition, we performed a systematic review of the literature in order to i) collect blood material for genetic studies of reported PK deficient cases lacking this information, and ii) perform a comprehensiv…

Pharmacokinetics of dabigatran etexilate and rivaroxaban in patients with short bowel syndrome requiring parenteral nutrition: The PDER PAN study

Background and aims: Patients on parenteral nutrition for short bowel syndrome (SBS) have a high risk of thrombotic complications and are often treated with parenteral anticoagulation. Direct oral anticoagulants are absorbed proximally in the digestive tract and may represent alternative regimens in selected SBS patients. In our pilot study, we provided pharmacokinetics parameters of dabigatran etexilate and rivaroxaban in this setting and compared peak (Cmax), trough (Ctrough) concentrations, and areas-under-the-concentration-time-curve (AUC(0) (-) (t)) to reference values retrieved from phase I-III studies. Methods: We enrolled 6 adults with a remaining small bowel length <= 200 cm, norma…

Determinants of the Quality of Warfarin Control and Validation of the SAMe-TT2-R2 Score for Acute Venous Thromboembolism. An Analysis of the Hokusai-VTE Trial