Clinical meaning
Factor V Leiden (FVL) is the most common inherited thrombophilia, caused by a single point mutation (G1691A) in the F5 gene that substitutes glutamine for arginine at position 506 (R506Q) of the Factor V protein. This amino acid substitution occurs at one of the three activated protein C (APC) cleavage sites on Factor V, rendering Factor Va RESISTANT to inactivation by activated protein C. Under normal hemostasis, the anticoagulant protein C (activated by thrombin bound to thrombomodulin on endothelial surfaces) cleaves and inactivates Factor Va and Factor VIIIa, serving as a critical negative feedback mechanism that limits thrombin generation and prevents pathological clot propagation. When Factor Va carries the Leiden mutation, APC cannot effectively cleave it at position 506, resulting in prolonged Factor Va activity, sustained prothrombinase complex (Factor Va + Factor Xa) activity, excessive thrombin generation, and a hypercoagulable state. FVL follows AUTOSOMAL DOMINANT inheritance and is the most prevalent inherited thrombophilia in Caucasian populations (~5% prevalence in European-descent populations, rare in Asian and African populations). HETEROZYGOUS carriers have a 3-8 fold increased risk of venous thromboembolism (VTE) compared...