Factor V variants in bleeding and thrombosis

Res Pract Thromb Haemost. 2024 Jan 26;8(1):102330. doi: 10.1016/j.rpth.2024.102330. eCollection 2024 Jan.ABSTRACTA state-of-the-art lecture titled "Factor V variants in bleeding and thrombosis" was presented at the International Society on Thrombosis and Haemostasis (ISTH) congress in 2023. Blood coagulation is a finely regulated cascade of enzymatic reactions culminating in thrombin formation and fibrin deposition at the site of injury. Factor V (FV) plays a central role in this process, as its activated form is an essential procoagulant cofactor in prothrombin activation. However, other molecular forms of FV act as anticoagulant cofactors of activated protein C and tissue factor pathway inhibitor α, respectively, thereby contributing to the regulation of coagulation. This dual procoagulant and anticoagulant character makes FV a central regulator of the hemostatic balance, and quantitative and qualitative alterations of FV may be associated with an increased risk of bleeding or venous thrombosis. Here, we review the procoagulant and anticoagulant functions of FV and the manifold mechanisms by which F5 gene mutations may affect the balance between these opposite functions and thereby predispose individuals to bleeding or venous thrombosis. In particular, we discuss our current understanding of the 3 main pathological conditions related to FV, namely FV deficiency, activated protein C resistance, and the overexpression of FV-short, a minor splicing isoform of FV with tissue f...
Source: Thrombosis and Haemostasis - Category: Hematology Authors: Source Type: research