Factor V Leiden MOA is associated with which mechanism?

• A. Resistance to protein C
• B. Increased effect of antithrombin
• C. Increased platelet aggregation
• D. Deficiency of protein S

Answer: (A)

Factor V Leiden causes resistance to activation‑protein C. A point mutation in factor V (R506Q) disrupts the proteolytic cleavage of factor Va by activated protein C, so factor Va remains active longer. With APC not properly inactivating Va (and with protein S as its cofactor), thrombin generation stays high, tipping the balance toward clot formation and causing inherited thrombophilia. This is why the mechanism is resistance to activated protein C. The other options don’t describe this APC‑resistance defect: antithrombin activity isn’t increased, platelet aggregation is not the primary driver here, and protein S deficiency is a separate cause of thrombophilia, not the characteristic mechanism of Factor V Leiden.