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Background: Asthma is associated with a prothrombotic state. Plasma factor VIIa-antithrombin complex concentrations (FVIIa-AT) indirectly reflect the interaction of tissue factor (TF) with FVII. Since TF is a key initiator of coagulation in vivo, we hypothesized that FVIIa-AT are higher in asthma.

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Mice with Reduced PAR4 Reactivity show Decreased Venous Thrombosis and Platelet Procoagulant Activity.

J Thromb Haemost

January 2025

Case Western Reserve University, School of Medicine, Department of Pharmacology, Cleveland, OH United States. Electronic address:

Background: Hypercoagulation and thrombin generation are major risk factors for venous thrombosis. Sustained thrombin signaling through PAR4 promotes platelet activation, phosphatidylserine exposure, and subsequent thrombin generation. A single-nucleotide polymorphism in PAR4 (rs2227376) changes proline to leucine extracellular loop 3 (P310L), which decreases PAR4 reactivity and is associated with a lower risk for venous thromboembolism (VTE) in a GWAS meta-analysis.

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Background: Tumour type, treatment and patient related factors contribute to cancer associated venous thromboembolism (VTE), however, the role of each factor and the mechanisms involved are not understood.

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Methods: Gynaecological cancer patients who developed VTE during follow-up (n = 59) (VTE+) were matched with treatment naïve(treatment (-)(VTE-)(n = 120) and chemotherapy treated patients(treatment (+)(VTE-) (n = 57)).

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Background:  Fibrinolysis is spatiotemporally well-regulated and greatly influenced by activated platelets and coagulation activity. Our previous real-time imaging analyses revealed that clotting commences on activated platelet surfaces, resulting in uneven-density fibrin structures, and that fibrinolysis initiates in dense fibrin regions and extends to the periphery. Despite the widespread clinical use of direct oral anticoagulants (DOACs), their impact on thrombin-dependent activation of thrombin-activatable fibrinolysis inhibitor (TAFI) and fibrinolysis remains unclear.

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Inherited factor VII deficiency is the most common rare bleeding disorder, affecting about 1/500,000 individuals without gender predilection. Most of the patients with FVII 20-50% are asymptomatic, but post-traumatic or post-surgical bleeding may often occur since there is not an exact correlation between FVII plasma levels and the bleeding phenotype. We enrolled 19 children and adolescents with FVII levels of 20-35% and 33 controls.

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