A 55-year-old woman presents with recurrent right leg deep vein thrombosis (DVT). Thrombophilia testing reveals homozygous Factor V Leiden mutation. She asks about the mechanism by which Factor V Leiden causes thrombophilia:

• A Factor V Leiden (R506Q mutation) renders Factor Va resistant to cleavage and inactivation by activated Protein C (APC resistance) ✓
• B Factor V Leiden causes elevated Factor V levels leading to excess thrombin generation
• C Factor V Leiden inhibits Protein S, reducing anticoagulant activity
• D Factor V Leiden activates Protein Z inhibitor pathway, bypassing normal coagulation

Explanation

Factor V Leiden is a single nucleotide polymorphism (R506Q — arginine to glutamine substitution at position 506) in the Factor V gene. This point mutation renders Factor Va resistant to proteolytic inactivation by activated Protein C (APC), a key natural anticoagulant mechanism. Normally, APC cleaves Factor Va at Arg506, Arg306, and Arg679; the R506Q mutation prevents initial cleavage at position 506, significantly impairing APC-mediated inactivation. The result is a hypercoagulable state — APC resistance. Heterozygosity increases DVT risk 3-8 fold; homozygosity increases it 50-80 fold.

Reference: Bailey & Love's Short Practice of Surgery, 27th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.