Factor V Leiden Mutation is the Most Common Inherited Cause of Thrombosis
The correct answer is D. Factor V Leiden (FV Leiden) Mutation is definitively the most common inherited cause of thrombosis. This is unequivocally established by multiple authoritative guidelines and represents fundamental knowledge in thrombophilia evaluation.
Epidemiologic Evidence
Factor V Leiden accounts for the vast majority of inherited thrombophilia cases:
- Factor V Leiden is present in approximately 5% of Caucasian Americans in the general population 1, 2
- It is found in 20% of patients presenting with idiopathic first venous thrombosis 1
- In pregnant women with venous thrombosis, Factor V Leiden is present in 60% of cases 1
- Factor V Leiden accounts for 85-95% of all patients with activated protein C resistance 2
Comparative Prevalence of Other Inherited Thrombophilias
The other inherited thrombophilias are significantly less common:
- Antithrombin III deficiency, Protein C deficiency, and Protein S deficiency collectively account for only 5-20% of venous thromboembolism patients 2
- Prothrombin G20210A mutation is the second most common inherited risk factor 1, 3, but still substantially less prevalent than Factor V Leiden
- Factor V Leiden was discovered in 1994 and immediately recognized as the most common genetic risk factor for venous thrombosis 1
Clinical Significance
Factor V Leiden creates a hypercoagulable state through a specific molecular mechanism:
- The mutation results in substitution of glutamine for arginine at position 506, making factor Va resistant to inactivation by activated protein C 2
- Heterozygotes have a 4- to 7-fold increased risk for initial venous thromboembolism 2, 4
- Homozygotes have an 80-fold increased risk for venous thromboembolism 2
Guideline Consensus
The American College of Medical Genetics explicitly states that Factor V Leiden is "the most common genetic risk factor for venous thrombosis" 1. This designation is reinforced by the EGAPP Working Group, which identifies Factor V Leiden as "the most common known inherited risk factor for thrombosis" 1.
Common Pitfall to Avoid
Do not confuse prevalence with clinical severity. While Antithrombin III deficiency may carry higher individual thrombotic risk, Factor V Leiden is far more prevalent in the population and among thrombosis patients, making it the most common inherited cause by frequency 1, 2.