TY - JOUR
T1 - Factor V variants in bleeding and thrombosis
AU - Mohapatra, Adarsh K.
AU - Todaro, Alice M.
AU - Castoldi, Elisabetta
N1 - Funding Information:
A.K.M. is an Early-Stage Researcher of the EU Horizon 2020 Innovative Training Network TICARDIO (Marie Sklodowska-Curie grant agreement No 813409). A.M.T. is supported by the Cardiovascular Research Institute Maastricht ( CARIM ).
Publisher Copyright:
© 2024 The Author(s)
PY - 2024/1/1
Y1 - 2024/1/1
N2 - A 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 a, 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 factor pathway inhibitor a–dependent anticoagulant properties and an emerging role as a key regulator of the initiation of coagulation. Finally, we summarize relevant new data on this topic presented during the 2023 ISTH Congress.
AB - A 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 a, 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 factor pathway inhibitor a–dependent anticoagulant properties and an emerging role as a key regulator of the initiation of coagulation. Finally, we summarize relevant new data on this topic presented during the 2023 ISTH Congress.
KW - bleeding
KW - factor V
KW - FV-short
KW - mutation
KW - venous thrombosis
U2 - 10.1016/j.rpth.2024.102330
DO - 10.1016/j.rpth.2024.102330
M3 - Article
SN - 2475-0379
VL - 8
JO - Research and practice in thrombosis and haemostasis
JF - Research and practice in thrombosis and haemostasis
IS - 1
M1 - 102330
ER -