Coagulation factor V Leiden (FVL) (FVL)

Coagulation factor V Leiden is a mutated form of human factor V that causes an increased tendency to form abnormal blood clots, a condition known as thrombophilia (StatPearls, 2023). The mutation involves a single nucleotide polymorphism (G1691A) in the F5 gene, resulting in the replacement of arginine with glutamine at position 506 (R506Q) (UniProt P12259). This specific site is one of the primary cleavage points for activated protein C (APC), which normally inactivates factor V to regulate the coagulation cascade (Mayo Clinic, 2023). Because factor V Leiden is resistant to APC-mediated degradation, it remains active longer in the circulation, promoting excessive thrombin generation and fibrin clot formation (MedlinePlus, 2020). While factor V Leiden itself is not typically the direct binding site for current pharmacological agents, it is the primary molecular driver for patients requiring long-term anticoagulant therapy. Management of individuals with this variant involves the use of direct oral anticoagulants (DOACs) or vitamin K antagonists to mitigate the elevated risk of venous thromboembolism, deep vein thrombosis, and pulmonary embolism (PubMed, PMID: 30893320). This target is critical in hematology for assessing genetic risk factors in patients with recurrent thrombosis and guiding the duration of anticoagulation.

Other names

Factor V R506QActivated protein C resistanceFV R506QFactor V G1691A mutationFVL

Anticoagulant drugs manage the effects of Factor V Leiden by inhibiting downstream proteases like Factor Xa or Thrombin, or by reducing the synthesis of vitamin K-dependent factors, thereby counteracting the hypercoagulability caused by activated protein C resistance (StatPearls, 2023).