Journal of Thrombosis and Haemostasis : JTH

The 2021 ASH ISTH NHF WFH guidelines recommendation that patients with VWF levels of 30-50 IU/dL and an increased bleeding phenotype be categorized as type 1 VWD rather than Low VWF has proved controversial. However, in support of that decision, recent data have demonstrated that individuals with partial quantitative VWF deficiency exhibit an age-dependent evolving phenotype and confirmed that Low VWF represents a sub-group within heterogeneous type 1 VWD. Nonetheless, type 1 VWD heterogeneity continues to pose significant diagnostic challenges...

BACKGROUND: Targeted long-read sequencing (LRS) is expected to comprehensively analyse diverse complex variants in haemophilia A (HA) and B (HB), caused by the F8 and F9 genes, respectively. However, its clinical applicability still requires extensive validation. OBJECTIVES: To evaluate the clinical applicability of targeted LRS-based analysis, compared with routine PCR-based methods. METHODS: Gene variants of retrieved subjects were retrospectively and prospectively analysed...

BACKGROUND: Myeloproliferative neoplasms (MPN) are characterized by a high rate of thrombotic complications that contribute to morbi-mortality. MPN-related thrombogenesis is assumed to be multifactorial involving both pro-coagulant and pro-inflammatory processes. Whether impaired fibrinolysis also participates in the pro-thrombotic phenotype of MPN has been poorly investigated. OBJECTIVES: We determined whether MPN, particularly JAK2V617F-positive MPN, are associated with fibrinolytic changes...

Many virus types affect the blood clotting system with correlations to pathology that range widely from thrombosis to haemorrhage linking to inflammation. Here we overview the intricate crosstalk induced by infection between proteins on the virus encoded by either the host or virus genomes, coagulation proteins, platelets, leukocytes, and endothelial cells. For blood-borne viruses with an outer covering acquired from the host cell, the envelope, a key player may be the cell-derived trigger of coagulation on the virus surface, tissue factor (TF)...

BACKGROUND: Although guidelines recommend risk assessment for hospital-acquired venous thromboembolism (HA-VTE) to inform prophylaxis decisions, studies demonstrate inappropriate utilization of pharmacoprophylaxis in hospitalized medical patients. Predictors of pharmacoprophylaxis initiation in medical inpatients remain largely unknown. OBJECTIVE: To determine factors associated with HA-VTE pharmacoprophylaxis initiation in adults hospitalized on medical services...

Cerebral venous sinus thrombosis (CVST) is an uncommon site of venous thromboembolism. CVST more commonly affects younger people and women, in stark contrast to other forms of venous thrombosis where incidence increases with age and overall affects men. Traditional risk factors for the development of CVST include endogenous and exogenous estrogen (combined oral contraceptives and pregnancy and the puerperium), thrombophilias and rare haematologic disorders. New and emerging risk factors include obesity, polycystic ovary syndrome, COVID-19 infection, and vaccine-induced thrombocytopenia and thrombosis (VITT) and VITT-like disorders...

BACKGROUND: A paucity of data exists to support the use of factor Xa inhibitors in severely obese patients with a weight ≥ 150kg or BMI ≥ 50 kg/m2 . OBJECTIVES: The purpose of this study is to evaluate whether factor Xa inhibitors are as safe and effective as warfarin for the treatment of atrial fibrillation (AF) and/or venous thromboembolism (VTE) in individuals with a BMI ≥ 50 kg/m2 and/or weight ≥ 150 kg. PATIENTS / METHODS: This was a multicenter retrospective cohort study of severely obese adult patients with AF and/or VTE treated with a factor Xa inhibitor or warfarin...

Endothelial cells deliver a vital contribution to the maintenance of hemostasis by constituting an anatomical as well as functional barrier between the blood and the rest of the body. Apart from the physical barrier function, endothelial cells maintain the hemostatic equilibrium by their pro- and anticoagulant functions. An important part of their procoagulant contribution is the production of von Willebrand factor (VWF), which is a carrier protein for coagulation factor VIII (FVIII) and facilitates the formation of a platelet plug...

BACKGROUND: Protein S (PS) is an anticoagulant that functions as a cofactor for activated protein C (APC) and tissue factor pathway inhibitor. PS deficiency is a risk factor for venous thromboembolism. PS activity is commonly measured using clot-based assays involving fibrin and thrombin production, but improvements are needed. OBJECTIVES: To develop a new assay for measuring plasma PS activity by quantifying the amount of activated coagulation factor V (FVa) cleaved by APC...

BACKGROUND: Almost half of severe hemophilia A (HA) cases are caused by an intron-22 inversion mutation (Int22Inv), which truncates the 26-exon F8 mRNA after exon 22. Another F8 transcript, F8B , is initiated from within F8-intron-22. F8B mRNA consists of a short exon spliced to exons 23-26 and is expressed in multiple human cell types. It has been hypothesized that Int22Inv patients have self-tolerance to partial FVIII proteins expressed from these two transcripts. FVIII is expressed in endothelial cells, primarily in liver and lung...

Direct Oral Anticoagulants (DOACs) are the first line anticoagulants for the secondary prevention of venous thromboembolism (VTE). However, patients with severe inherited thrombophilias represent a group where the efficiency and safety of DOACs is poorly studied. In this communication, we focus on the utility of DOACs in the secondary prevention of VTE in patients with severe thrombophilia. Current evidence is based only on cohort or single center studies, and poor data is available on compliance of the patients in the studies...

BACKGROUND: Continuously improving cancer-specific survival puts a growing proportion of cancer patients at risk of major adverse cardiovascular events (MACE), but tailored tools for cardiovascular risk prediction remain unavailable. OBJECTIVES: To assess a broad panel of cardiovascular biomarkers and risk factors for the prediction of MACE and cardiovascular death in cancer patients. METHODS: In total, 2192 patients with newly diagnosed or recurrent cancer were followed prospectively for the occurrence of 2-year MACE and 5-year cardiovascular death...

BACKGROUND: Patients with primary immune thrombocytopenia (ITP) have an increased risk of thrombosis, which may be due to altered fibrinolysis. OBJECTIVES: To elucidate the clinical impact of delayed fibrinolysis in ITP patients. METHODS: A turbidimetric clot formation and lysis assay and a fluorometric plasmin generation (PG) assay were performed and levels of plasminogen-activator-inhibitor-1 (PAI-1), tissue-plasminogen-activator (tPA), tPA-PAI-1 complexes, α2-antiplasmin, TAFI and D-Dimer were assessed in 86 adult primary ITP patients and 78 healthy controls (HC)...

Ovarian vein thrombosis (OVT) is a rare but potentially serious condition. We conducted a scoping review of published data to provide a better understanding of OVT management. MEDLINE and Cochrane databases were searched. Eligibility criterion was original articles including women with OVT until May 2024. Quantitative data were pooled via CMA software. Quality of the primary studies was assessed via the Newcastle‒Ottawa Scale. Out of 1,007 identified records, 19 primary studies including 1,128 patients were selected...

BACKGROUND: Hematopoietic transcription factor RUNX1 is expressed from proximal P2 and distal P1 promoter to yield isoforms RUNX1 B and C, respectively. The roles of these isoforms in RUNX1 autoregulation and downstream-gene regulation in megakaryocytes and platelets are unknown. OBJECTIVES: To understand the regulation of RUNX1 and its target genes by RUNX1 isoforms. METHODS: We performed studies on RUNX1 isoforms in megakaryocytic HEL cells and HeLa cells (lack endogenous RUNX1), in platelets from 85 healthy volunteers administered aspirin or ticagrelor, and on the association of RUNX1 target genes with acute events in 587 patients with cardiovascular disease (CVD)...

BACKGROUND: Anticoagulation and antiplatelet therapy effectively inhibit neointimal hyperplasia (NIH) in both arterial and venous systems but not in arteriovenous fistulae (AVF). The main site of AVF failure is the juxta-anastomotic area that is characterized by disturbed flow compared with laminar flow in the arterial inflow and the venous outflow. OBJECTIVES: We hypothesized that early thrombus formation is required for eccentric and heterogeneous NIH in the presence of disturbed flow...

BACKGROUND: Normothermic machine perfusion (NMP) is used for preservation and assessment of human donor livers prior to transplantation. During NMP, the liver is metabolically active, which allows detailed studies on the physiology of human livers. OBJECTIVES: To study the production of hemostatic proteins in human donor livers during NMP for up to 7 days. METHODS: In this observational study, nine livers underwent NMP for up to 7 days with a heparinised perfusate based on red blood cells and colloids using a modified Liver Assist device...

Platelets navigate the fine balance between homeostasis and injury. They regulate vascular homeostasis and drive repair post-injury amidst leukocyte extravasation. Crucially, platelets initiate extracellular traps generation and promote immunothrombosis. In chronic human diseases, platelet action often extends beyond its normative role, sparking sustained reciprocal activation of leukocytes and mural cells, culminating in adverse vascular remodeling. Studies in the last decade have spotlighted a novel key player in platelet activation, the high mobility group box 1 (HMGB1) protein...

BACKGROUND: Gene therapy is designed to provide people with haemophilia B with a steady and elevated factor IX activity, thereby strengthening protection and relieving the burden of replacement therapy frequent infusions. The European Medicines Agency has approved a gene therapy for the severe and moderately severe forms of haemophilia B that uses the factor IX Padua variant (etranacogene dezaparvovec). The aim is to provide a document dedicated to haemophilia B gene therapy and give a comprehensive overview of the topic...

BACKGROUND: CpG ODN are synthetic single stranded DNA sequences that act as immunostimulants. They have been increasingly used to treat several cancers, however, thrombocytopenia is a potential recognized side effect of some sequences. OBJECTIVES: We tested the ability of two CpG ODN (ODN 2395 and ISIS 120704) to induce thrombocytopenia when administered to BALB/c mice and determined mechanisms associated with thrombocytopenia. METHODS: BALB/c mice were pre-bled and then injected with titrated doses of CpG ODNs and platelet counts were determined...