Functional assessment of genetic variants in thrombomodulin detected in patients with bleeding and thrombosis.

Thrombomodulin (TM) expressed on endothelial cells regulates coagulation. Specific nonsense variants in the TM gene, THBD, result in high soluble TM levels causing rare bleeding disorder. In contrast, though THBD variants have been associated with venous thromboembolism, this association remains controversial.

Multi-Gene Panel for Thrombophilia Testing in Venous Thromboembolism.

Background: Conventional tests for inherited thrombophilia focus on the five most-established inherited thrombophilias; i.e. deficiencies in antithrombin, protein C, and protein S, and the factor V Leiden and prothrombin G20210A variants.

Peptidylarginine deiminase 4 and ADAMTS13 activity in bacteraemia.

infection is associated with increased levels of neutrophil extracellular traps (NETs) and von Willebrand factor (VWF), and with reduced activity of ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motifs, member 13). Peptidylarginine deiminase 4 (PAD4) contributes to NET formation and inactivates ADAMTS13 . The role of PADs in the dynamics of NETs, VWF and ADAMTS13 has not yet been studied.

Management of Bleeding and Hemolysis During Percutaneous Microaxial Flow Pump Support: A Practical Approach.

Percutaneous ventricular assist devices (pVADs) are increasingly being used because of improved experience and availability. The Impella (Abiomed), a percutaneous microaxial, continuous-flow, short-term ventricular assist device, requires meticulous postimplantation management to avoid the 2 most frequent complications, namely, bleeding and hemolysis. A standardized approach to the prevention, detection, and treatment of these complications is mandatory to improve outcomes.

Emicizumab for acquired haemophilia A: A case series.

Background: Emicizumab is approved to prevent bleeding in patients with congenital haemophilia A with or without inhibitors. However, no randomized trials addressed the efficacy of emicizumab in acquired haemophilia A (AHA).

Aims: To report the clinical and biochemical response of emicizumab in AHA.

Impairment of Angiogenesis-Driven Clot Resolution Is a Key Event in the Progression to Chronic Thromboembolic Pulmonary Hypertension: Validation in a Novel Rabbit Model.

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening condition and rare complication of acute pulmonary embolism. Mechanisms underlying impaired clot resolution and in sustained fibrothrombotic obstruction of the pulmonary arterial bed remain poorly understood. Since defective angiogenesis correlated to defective clot resolution based on observations in surgical material from patients with CTEPH, we aimed to validate its crucial pathogenic role by intrathrombus inhibition of angiogenesis in a novel CTEPH rabbit model.

Clinical application of multigene panel testing for bleeding, thrombotic, and platelet disorders: a 3-year Belgian experience.

Background: The international study ThromboGenomics has evaluated the diagnostic rate using a targeted multigene panel test for the screening of inherited bleeding, thrombotic and platelet disorders.

Objectives: We retrospectively analyzed the results of the implementation of genetic testing for inherited bleeding, thrombotic and platelet disorders in Belgian clinical practice and evaluated possible reclassification of reported variants.

Patients/methods: We implemented a Thrombosis-Hemostasis multigene panel test using whole exome sequencing to diagnose 487 patients recruited by 27 different Belgian hospitals with the implementation of stringent laboratory accreditation standards and by studying up to 100 diagnostic-grade genes.

Pro-haemostatic effect of DDAVP is partially derived through non-classical (CD14 /CD16 ) monocytes residing the spleen.

The splenic endothelial Weibel-palade bodies are one of the most important candidate organelles to release von Willebrand factor upon stimulation with desmopressin. However, the presence of functional desmopressin-specific receptor has not yet been demonstrated on endothelial cells. Experimental evidences are in favour of an indirect pro-haemostatic effect of desmopressin, but the exact mediator and its cellular origin are largely elusive.

Dysregulation of the kallikrein-kinin system in bronchoalveolar lavage fluid of patients with severe COVID-19.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) binds to the angiotensin-converting enzyme 2 (ACE2) receptor, a critical component of the kallikrein-kinin system. Its dysregulation may lead to increased vascular permeability and release of inflammatory chemokines. Interactions between the kallikrein-kinin and the coagulation system might further contribute to thromboembolic complications in COVID-19.

Apixaban in a porcine model of mechanical valve thrombosis in pulmonary position-a pilot study.

Objectives: The newest mechanical valves have low thrombogenicity, making them candidates for anticoagulation with a direct oral anticoagulant. While these drugs hold great promise to replace warfarin, clinical trials have been disappointing so far. We aimed to evaluate apixaban in a porcine model of mechanical valve thrombosis with On-X® (CryoLife) aortic valves implanted in pulmonary position.

Factor VIII-Fc Activates Natural Killer Cells Fc-Mediated Interactions With CD16.

The most challenging complication associated with Factor VIII (FVIII) replacement therapy is the development of neutralizing anti-drug antibodies, or inhibitors, which occur in 23-35% of severe (FVIII level <1%) hemophilia A (HA) patients and are a serious hindrance to effective management of HA. Consequently, strategies that can either prevent anti-FVIII inhibitors from developing or "tolerize" individuals who develop such antibodies represent a clinically important unmet need. One intervention for patients with high-titer inhibitors is immune tolerance induction (ITI) therapy.

Venous Thromboembolism in Patients Discharged after COVID-19 Hospitalization.

Background:  Venous thromboembolism (VTE) is a frequent complication of COVID-19, so that the importance of adequate in-hospital thromboprophylaxis in patients hospitalized with COVID-19 is well established. However, the incidence of VTE after discharge and whether postdischarge thromboprophylaxis is beneficial and safe are unclear. In this prospective observational single-center study, we report the incidence of VTE 6 weeks after hospitalization and the use of postdischarge thromboprophylaxis.

Coagulation Factors Accumulate During Normothermic Liver Machine Perfusion Regardless of Donor Type and Severity of Ischemic Injury.

Background: Coagulation factors may inform on liver function during normothermic machine perfusion (NMP). We investigated whether graft ischemic injury impairs the accumulation of anticoagulation factors during NMP of porcine and human livers.

Methods: Dynamics of FV, FVII, FVIII, FIX, and FX during NMP and their correlation with graft injury was investigated in porcine livers with minimal (no warm ischemia, n = 5) or severe injury (60 min warm ischemia, n = 5).

Apixaban in patients on haemodialysis: a single-dose pharmacokinetics study.

Background: Apixaban, a direct oral anticoagulant inhibiting factor Xa, has been proven to reduce the risk of atrial fibrillation-related stroke and thromboembolism in patients with mild to moderate renal insufficiency. Patients on renal replacement therapy, however, were excluded from randomized controlled trials. Therefore, uncertainty remains concerning benefits, dosing and timing of intake in haemodialysis population.

Optimization of the detection of inhibitory autoantibodies against the VWF-cleaving protease ADAMTS13 with an automated chemiluminescent ADAMTS13 activity immunoassay.

Introduction: Acquired thrombotic thrombocytopenic purpura is a rare disease associated with the production of autoantibodies against the VWF-cleaving protease ADAMTS13. The detection of these antibodies is made difficult by the instability of ADAMTS13 in citrated plasma and the time-consuming ADAMTS13 assays. The aim of our study was to evaluate the optimal conditions for detecting anti-ADAMTS13 inhibitory antibodies with the novel automated chemiluminescent immunoassay HemosIL AcuStar ADAMTS13 Activity assay.

Von Willebrand factor and ADAMTS13 impact on the outcome of Staphylococcus aureus sepsis.

Background: Previous clinical evidence correlates levels of von Willebrand factor (VWF) and its cleaving protease ADAMTS13 with outcome in septic patients. No previous studies addressed if VWF and ADAMTS13 affected the outcome of Staphylococcus aureus sepsis.

Objectives: We studied the role of VWF and ADAMTS13 in S.

Accurate measurement of extended half-life and unmodified factor VIII low levels with one-stage FVIII assays is dependent on the matrix of calibration curves.

Introduction: The monitoring of factor VIII (FVIII) replacement therapy relies on the accurate measurement of FVIII activity over a large concentration range. However, unexplained overestimation of low FVIII levels has recently been reported with extended half-life recombinant FVIIIs.

Aim: The objective of this study was to confirm previous publications indicating that the reagents used to generate the calibration curves determine the accuracy of the measurement of low FVIII levels.

Pure ultra-fine carbon particles do not exert pro-coagulation and inflammatory effects on microvascular endothelial cells.

Pro-thrombotic and inflammatory changes play an important role in cardiovascular morbidity and mortality, resulting from short-term exposure to fine particulate air-pollution. Part of those effects has been attributed to the ultra-fine particles (UFPs) that pass through the lung and directly contact blood-exposed and circulating cells. Despite UFP-induced platelet activation, it is unclear whether the penetrated particles exert any direct effect on endothelial cells.

Targeting Coagulase Activity in Staphylococcus aureus Bacteraemia: A Randomized Controlled Single-Centre Trial of Staphylothrombin Inhibition.

Background: () bacteraemia is frequent and carries a high morbidity and mortality. Coagulases secreted by initiate blood coagulation by directly activating prothrombin. This pathogen-activated coagulation is insensitive to most antithrombotic drugs, with the exception of small molecule direct thrombin inhibitors (DTIs).

Biodistribution of Liver-Derived Mesenchymal Stem Cells After Peripheral Injection in a Hemophilia A Patient.

Background: With the exception of liver transplantation, there is no cure for hemophilia, which is currently managed by preemptive replacement therapy. Liver-derived stem cells are in clinical development for inborn and acquired liver diseases and could represent a curative treatment for hemophilia A. The liver is a major factor VIII (FVIII) synthesis site, and mesenchymal stem cells have been shown to control joint bleeding in animal models of hemophilia.