Accurate evaluation of factor VIII activity of efanesoctocog alfa in the presence of emicizumab.

Background: Efanesoctocog is a B-domain-deleted, Fc-fusion FVIII linked to the D'D3 domain of VWF and two XTEN polypeptides, designed for an ultra-extended half-life for prophylaxis in hemophilia A, but also aiding in managing acute bleeding or surgery in patients on long-term emicizumab. However, no current laboratory method accurately measures FVIII levels in the presence of emicizumab. We hypothesized that the chromogenic (CSA) FVIII assay, specifically calibrated for efanesoctocog using bovine coagulation factors, could provide an accurate assessment of efanesoctocog activity.

Von Willebrand factor for outcome prediction within different clinical stages of advanced chronic liver disease.

Background And Aims: The prognostic performance of von Willebrand factor (VWF) may vary across clinical stages of advanced chronic liver disease (ACLD). Therefore, we investigated the evolution of VWF and other biomarkers throughout the full ACLD spectrum and evaluated their stage-specific prognostic utility.

Methods: We retrospectively included Viennese ACLD patients with available information on hepatic venous pressure gradient (HVPG), C-reactive protein (CRP)/VWF levels and outcomes.

Platelet adhesion assessed by PFA-100 is not linked to progression of ACLD.

Background & Aims: Increased aggregation of individual platelets upon activation, as assessed by whole blood aggregometry standardised to platelet count (PLT), has recently been linked to progression of advanced chronic liver disease (ACLD). Moreover, changes in primary haemostasis have been implicated in bleeding and thrombosis in patients with ACLD.We aimed (i) to identify the determinants of the primary haemostatic capacity - as assessed by Platelet Function Analyzer 100 (PFA-100) (' bleeding time') - in patients with ACLD and (ii) to investigate its potential association with clinical outcomes.

Concentration-effect relationship for tranexamic acid inhibition of tissue plasminogen activator-induced fibrinolysis in vitro using the viscoelastic ClotPro® TPA-test.

Background: Tranexamic acid is an antifibrinolytic drug that is commonly administered for obstetric haemorrhage. Conventional viscoelastic tests are not sensitive to tranexamic acid, but the novel ClotPro® TPA-test can measure tranexamic acid-induced inhibition of fibrinolysis. We aimed to evaluate the TPA-test in pregnant and non-pregnant women.

Prevalence of FXII-Deficiency and Its Relevance to Monitoring Anticoagulation in Adults Receiving Extracorporeal Membrane Oxygenation.

During extracorporeal membrane oxygenation (ECMO) blood is exposed to artificial surfaces, resulting in contact activation of the intrinsic coagulation pathway initiated by coagulation factor XII (FXII). Little is known about the prevalence of acquired FXII-deficiency, especially during ECMO. The primary outcome was the prevalence of acquired FXII-deficiency (FXII activity <60%) during ECMO.

Prevalence and Impact of Lupus Anticoagulant in Patients Receiving Extracorporeal Membrane Oxygenation.

Background: Monitoring of blood coagulation is essential in ECMO patients. We investigated the prevalence of lupus anticoagulant (LA) and its association with coagulation testing and hemostaseologic complications in patients treated with ECMO.

Methods: This is a retrospective analysis including adult patients who received ECMO at a medical intensive care unit at the Medical University of Vienna.

The necessity of repeat testing for von Willebrand disease in adult patients with mild to moderate bleeding disorders.

Background: In patients with mild-to-moderate bleeding disorders (MBD), von Willebrand disease (VWD) is diagnosed at von Willebrand factor (VWF) levels ≤50 IU/dL. Although VWF levels are unstable, repeated testing for VWD diagnosis is not necessarily advised in recent guidelines.

Objectives: To analyze the relevance of repeated VWF testing to diagnose VWD in patients with MBD.

Von Willebrand factor processing in patients with advanced chronic liver disease and its relation to portal hypertension and clinical outcome.

Background And Aims: Endothelial dysfunction and portal hypertension (PH) are reflected by increased von Willebrand factor antigen (VWF-Ag) levels in advanced chronic liver disease (ACLD). This study investigated VWF release and cleavage and their association with PH and clinical outcomes.

Methods: Levels of VWF-Ag, VWF-N (VWF-propeptide), and VWF-A (VWF processed by the main VWF-cleaving protease ADAMTS13) were assessed in 229 patients with clinically stable ACLD (hepatic venous pressure gradient [HVPG] ≥ 6 mmHg; absence of bacterial infections or acute decompensation) undergoing HVPG-measurement.

Bleeding phenotype in nonsevere hemophilia by International Society on Thrombosis and Haemostasis bleeding assessment tool, bleeding frequency, and the joint status.

Background: Although the phenotype of severe hemophilia has been well studied, there are still knowledge gaps in nonsevere hemophilia.

Objectives: The objective of this study was to characterize the clinical bleeding phenotype in nonsevere hemophilia and its association with different factor VIII/IX assessments.

Methods: This was a cross-sectional, multicenter study to investigate the bleeding phenotype in adults with nonsevere hemophilia by the number of bleeding and joint bleeding in the past 5 years, a joint score, and the International Society on Thrombosis and Haemostasis bleeding assessment tool (ISTH-BAT).

Characterization of a prothrombotic phenotype using thrombin generation and thrombin activity in cirrhosis and portal hypertension.

Background: Patients with advanced chronic liver disease (ACLD) may develop a prothrombotic phenotype that seems to be more pronounced with more severe liver dysfunction. An imbalance of endogenous pro- and anticoagulants is not fully captured by routine coagulation assays.

Methods: In a cohort of ACLD patients undergoing hepatic venous pressure gradient (HVPG) measurement, we assessed thrombin generation (TGA) using two commercially available assays (Technothrombin and Thrombinoscope) with and without addition of soluble thrombomodulin (TM), as well as thrombin activity, alongside a panel of coagulation parameters.

Antithrombin Activity and Association with Risk of Thrombosis and Mortality in Patients with Cancer.

Venous and arterial thromboembolism (VTE/ATE) are common complications in cancer patients. Antithrombin deficiency is a risk factor for thrombosis in the general population, but its connection to risk of cancer-associated thrombosis is unclear. We investigated the association of antithrombin activity levels with risk of cancer-associated VTE/ATE and all-cause mortality in an observational cohort study including patients with cancer, the Vienna Cancer and Thrombosis Study.

The Sequential Application of Baveno VII Criteria and VITRO Score Improves Diagnosis of Clinically Significant Portal Hypertension.

Background & Aims: Baveno VII proposed liver stiffness measurement (LSM)/platelet count (PLT)-based criteria ('ruled out,' LSM ≤15 kPa plus PLT ≥150 G/L; 'ruled in': LSM ≥25 kPa) for clinically significant portal hypertension (CSPH) in compensated advanced chronic liver disease (cACLD). However, a substantial proportion of patients remains 'unclassified.'

Methods: Patients with evidence of cACLD (LSM ≥10 kPa) undergoing hepatic venous pressure gradient (HVPG) measurement at the Vienna General Hospital 2004 to 2021 (derivation [2004-2016], n = 221; validation [2017-2021], n = 81) were included.

Increasing test specificity without impairing sensitivity: lessons learned from SARS-CoV-2 serology.

Background: Serological tests are widely used in various medical disciplines for diagnostic and monitoring purposes. Unfortunately, the sensitivity and specificity of test systems are often poor, leaving room for false-positive and false-negative results. However, conventional methods were used to increase specificity and decrease sensitivity and vice versa.

Clinical significance of substantially elevated von Willebrand factor antigen levels in patients with advanced chronic liver disease.

Background: Von Willebrand factor antigen (VWF) is a non-invasive marker for clinically significant portal hypertension (HVPG≥10 mmHg) and confers HVPG-independent prognostic information. While quantification of increased VWF-levels is not relevant in the context of von Willebrand disease, highly elevated VWF may be of clinical significance in ACLD. Thus, we have modified our analytical approach to quantify very high VWF-levels (i.

Assay validity of point-of-care platelet function tests in thrombocytopenic blood samples.

Introduction: Point-of-care (POC) platelet function tests are faster and easier to perform than in-depth assessment by flow cytometry. At low platelet counts, however, POC tests are prone to assess platelet function incorrectly. Lower limits of platelet count required to obtain valid test results were defined and a testing method to facilitate comparability between different tests was established.

The VWF binding aptamer rondoraptivon pegol increases platelet counts and VWF/FVIII in type 2B von Willebrand disease.

Type 2B von Willebrand disease (VWD) is characterized by an increased binding affinity of von Willebrand factor (VWF) to platelet glycoprotein Ib. This can lead to clearance of high-molecular-weight (HMW) multimers and thrombocytopenia with a resulting moderate-severe bleeding phenotype. Rondoraptivon pegol (BT200) is a pegylated aptamer binding to the A1 domain of VWF with a novel mechanism of action: it enhances VWF/factor VIII (FVIII) levels by decreasing their clearance.

Absorption of Direct Oral Anticoagulants in Cancer Patients after Gastrectomy.

Direct oral anticoagulants (DOACs) are safe and effective in cancer patients treated for venous thromboembolism (VTE) or atrial fibrillation (AF). Gastrectomy is the treatment of choice in patients with localized upper gastrointestinal cancer. DOACs are absorbed in the upper gastrointestinal tract, but to what extent is unclear.

Multicenter performance evaluation and reference range determination of a new one-stage factor VIII assay.

Introduction: We conducted a multicenter evaluation of a new one-stage factor VIII (FVIII) assay (Roche Diagnostics), intended for the quantitative assessment of FVIII activity. We evaluated the analytical performance of the FVIII assay on the cobas t 711 analyzer.

Methods: Experiments performed at three laboratories used 3.

Factor VIII/protein C ratio independently predicts liver-related events but does not indicate a hypercoagulable state in ACLD.

Background & Aims: It has been suggested that the ratio of procoagulant factor VIII to anticoagulant protein C (FVIII/PC) reflects the hemostatic equilibrium. Moreover, FVIII/PC predicted decompensation/death in a small study not accounting for portal hypertension severity. We investigated (i) the prognostic value of FVIII/PC (outcome-cohort) and (ii) whether FVIII/PC reflects the hypercoagulable state (assessed by thrombomodulin-modified thrombin generation assay [TM-TGA]) or the risk of bleeding/thrombotic events in patients undergoing hepatic venous pressure gradient (HVPG) measurement during follow-up.