Journal of Thrombosis and Haemostasis : JTH

Based on emerging evidence from the COVID-19 pandemic, the International Society on Thrombosis and Haemostasis (ISTH) guidelines for antithrombotic treatment in COVID-19 were published in 2022. Since then, at least 16 new randomized controlled trials have contributed additional evidence, which necessitated a modification of most of the previous recommendations. We used again the American College of Cardiology Foundation/American Heart Association methodology for assessment of level of evidence (LOE) and class of recommendation (COR)...

BACKGROUND: Scott syndrome is a mild platelet-type bleeding disorder, first described in 1979, with only 3 unrelated families identified through defective phosphatidylserine (PS) exposure and confirmed by sequencing. The syndrome is distinguished by impaired surface exposure of procoagulant PS on platelets after stimulation. To date, platelet function and thrombin generation in this condition have not been extensively characterized. OBJECTIVES: Genetic and functional studies were undertaken in a consanguineous family with a history of excessive bleeding of unknown cause...

BACKGROUND: Deep venous thrombosis (DVT) is a common vascular event that can result in debilitating morbidity and even death due to pulmonary embolism. Clinically, patients with faster resolution of a venous thrombus have improved prognosis, but the detailed structural information regarding changes that occur in a resolving thrombus over time is lacking. OBJECTIVE: To define the spatial-morphological characteristics of venous thrombus formation, propagation, and resolution at the submicron level over time...

BACKGROUND: No F8 genetic abnormality is detected in approximately 1% to 2% of patients with severe hemophilia A (HA) using conventional genetic approaches. In these patients, deep intronic variation or F8 disrupting genomic rearrangement could be causal. OBJECTIVES: The study aimed to identify the causal variation in families with a history of severe HA for whom genetic investigations failed. METHODS: We performed whole F8 gene sequencing in 8 propositi...

BACKGROUND: The 2023 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) antiphospholipid syndrome (APS) classification criteria were developed with higher specificity but lower sensitivity compared with the 2006 Sydney revised classification criteria. OBJECTIVES: To validate the performance of the 2023 ACR/EULAR APS classification criteria in a large Chinese APS cohort. METHODS: This was a single-center cohort study...

BACKGROUND: The widespread use of the anti-fibrinolytic agent, tranexamic acid (TXA), interferes with the quantification of fibrinolysis by dynamic laboratory assays such as clot lysis, making it difficult to measure fibrinolysis in many trauma patients. At the final stage of coagulation, Factor XIIIa (FXIIIa) catalyses the formation of fibrin-fibrin and fibrin-α2 -antiplasmin (α2 AP) cross-links which increases clot mechanical strength and resistance to fibrinolysis. OBJECTIVES: Here, we develop a method to quantify fibrin-fibrin and fibrin-α2 AP cross-links that avoids the challenges posed by TXA in determining fibrinolytic resistance in conventional assays...

Platelets are well-known players in several cardiovascular diseases such as atherosclerosis and venous thrombosis. There is increasing evidence demonstrating that reactive oxygen species (ROS) are generated within activated platelets. Nicotinamide adenine dinucleotide phosphate oxidase (NOX) is a major source of ROS generation in platelets. Ligand binding to platelet receptor glycoprotein (GP) VI stimulates intracellular ROS generation consisting of a spleen tyrosine kinase-independent production involving NOX activation and a following spleen tyrosine kinase-dependent generation...

BACKGROUND: Until recently, the treatment of hemophilia A relied on FVIII replacement. However, up to 1/3 of patients with severe hemophilia A develop neutralizing alloantibodies that render replacement therapy ineffective. The development of emicizumab, a bispecific antibody that partially mimics FVIIIa, has revolutionized the treatment of these patients. However, the use of an activated prothrombin complex concentrate (FEIBA®) to treat breakthrough bleeding in patients on emicizumab has been associated with thrombotic complications including a unique microangiopathy...

BACKGROUND: Coagulopathy is a major cause of morbidity and mortality in COVID-19 patients. Hypercoagulability in COVID-19 results in deep vein thrombosis, thromboembolic complications, and diffuse intravascular coagulation. Microbiome dysbiosis influences the clinical course of COVID-19. However, the role of dysbiosis in COVID-19-associated coagulopathy is not fully understood. OBJECTIVES: The present study tested the hypothesis that the microbiota-derived proapoptotic corisin is involved in the coagulation system activation during SARS-CoV-2 infection...

BACKGROUND: There are very few large population-based studies studying mental health in persons with von Willebrand disease (PwVWD). OBJECTIVES: We aim to assess prevalence of depression and anxiety in PwVWD over a period of 20 years and identify bleeding symptoms that may be more likely associated with depression and anxiety in PwVWD. METHODS: This is a retrospective cohort study using a deidentified national dataset from 1118 hospitals with 176 million patients...

BACKGROUND: Antibodies against factor VIII (FVIII) are a major complication in the treatment of patients with severe hemophilia A (HA). The Nijmegen Bethesda assay (NBA) is the gold standard for detection of neutralizing antibodies (inhibitors). Whereas both, inhibitors and non-neutralizing antibodies (NNAbs) can be detected by immunoassays such as enzyme-linked immunosorbent assay (ELISA) and multiplex Luminex™ bead-based assays. AIM: Evaluation of an in-house Luminex™ bead-based assay (LumiTope) in comparison to a commercially available ELISA and NBA...

Coagulopathy alongside micro- and macrovascular thrombotic events were frequent characteristics of patients presenting with acute COVID-19 during the initial stages of the pandemic. However, over the past 4 years, the incidence and manifestations of COVID-19-associated coagulopathy have changed due to immunity from natural infection and vaccination, and the appearance of new SARS-CoV-2 variants. Diagnostic criteria and management strategies based on early experience and studies for COVID-19-associated coagulopathy thus require re-evaluation...

BACKGROUND: The platelet-driven contraction or retraction of blood clots has been utilized to obtain blood serum for laboratory studies, but now in vitro clot contraction assays are used in research laboratories and clinics to assess platelet functionality. The static final extent of clot contraction measured using a clot size or expelled serum volume can be supplemented substantially with a dynamic analysis. OBJECTIVES: To provide a step-by-step protocol for a relatively simple and affordable new automated methodology to follow the kinetics of blood clot contraction, which allows for simultaneous measurements of various samples at a time and requires only a fluorescence plate reader...

BACKGROUND: Relatively little is known about thrombotic adverse events (AEs) of emicizumab in postmarketing real-world settings, particularly in comparison with factor VIII (FVIII) products. A recent European study reported a potentially greater thrombotic risk of emicizumab compared with FVIII products. OBJECTIVES: This drug safety study aims to investigate whether thrombotic AEs are more frequently reported for emicizumab than for FVIII products and if so, whether it is independent of bypassing agents as coreporting drugs using the United States Food and Drug Administration Adverse Event Reporting System data...

BACKGROUND: Extracellular traps formed by neutrophils (NETs) and eosinophils (EETs) have been described in coronary thrombi, contributing to thrombus stability. A key mechanism during NET formation is histone modification by the enzyme PAD4. Citrullinated histones, the product of PAD4 activity, are often attributed to neutrophils. Eosinophils also express high levels of PAD4 but the contribution of PAD4 to EET formation is not known. METHODS: We performed immunohistological analyses on thrombi, including a large, intact and eosinophil-containing thrombus retrieved from the right coronary artery using an aspiration catheter and stroke thrombi from thrombectomy retrieval...

BACKGROUND: Thrombin generation (TG) is used as a global test of coagulation, and is an indicator of thrombosis and bleeding risk. Until now, data on the association of TG and mortality is inconclusive. We investigated the association of TG and mortality in the prospective Moli-sani cohort (n=21,920). METHODS: TG was measured using calibrated automated thrombinography using PPP reagent low. Lag time (LT), endogenous thrombin potential (ETP), peak height, time-to-peak (TTP) and velocity index (VI) were quantified...

BACKGROUND: At sites of vessel injury, thrombin acts as the central mediator of coagulation by catalyzing fibrin clot formation and platelet activation. Thrombin generation is most frequently measured in plasma samples using small-molecule substrates; however, these have low specificity for thrombin and limited utility in whole blood. Plasma assays are limited because they ignore the hemostatic contributions of blood cells and require anticoagulation and the addition of supraphysiological concentrations of calcium...

Inflammation and coagulation are critical self-defense mechanisms for mitigating infection that can nonetheless induce tissue injury and organ dysfunction. In severe cases, like sepsis, a dysregulated thromboinflammatory response may result in multiorgan dysfunction. Sepsis-associated acute kidney injury (AKI) is a significant contributor to patient morbidity and mortality. The connection between AKI and thromboinflammation is largely due to unique aspects of the renal vasculature. Specifically, the interaction between blood cells with the endothelial, glomerular, and peritubular capillary systems during thromboinflammation reduces oxygen supply to tubular epithelial cells...

BACKGROUND: Cancer patients have an increased risk of developing coagulation complications, and chemotherapy treatment increases the risk. Tumor progression is closely linked with the hemostatic system. Breast cancer tumors express coagulation factor V (FV), an essential factor in blood coagulation. The functional role of FV during treatment with chemotherapy is poorly understood and were explored in this study. OBJECTIVES: We aimed to investigate the role of FV in breast cancer progression by exploring associations to treatment response, gene regulation and the functional effects of FV...

BACKGROUND: Immune-mediated thrombotic thrombocytopenic purpura is caused by autoantibodies against ADAMTS-13, a plasma enzyme that cleaves von Willebrand factor. However, the mechanism resulting in severe deficiency of plasma ADAMTS-13 activity remains controversial. OBJECTIVES: To determine the mechanism of autoantibody-mediated severe deficiency of plasma ADAMTS13 activity in immune-mediated thrombotic thrombocytopenic purpura. METHODS: Fluorescence resonance energy transfer-VWF73 was used to determine plasma ADAMTS-13 activity...