A 52-year-old man with a history of recurrent deep vein thrombosis presents to the hematology clinic. During investigation of his thrombophilia, various coagulation factors are measured. Which of the following is the most common inherited thrombophilic defect in the Indian population?

Explanation

## Most Common Inherited Thrombophilia in the Indian Population **High-Yield:** Factor V Leiden (FVL) mutation is the most common inherited thrombophilic defect globally and is also the most frequently identified inherited thrombophilia in Indian thrombophilia cohorts, though its prevalence is lower than in Caucasian populations (~1–5% in Indians vs. 5–8% in Caucasians). **Key Point:** Factor V Leiden is a point mutation (G1691A) in the Factor V gene that renders Factor Va resistant to inactivation by Activated Protein C (APC resistance). This leads to sustained thrombin generation and a 5–7× increased risk of venous thromboembolism in heterozygotes. ### Comparison of Common Inherited Thrombophilias | Defect | Prevalence in Indians | Relative Risk | Mechanism | |--------|----------------------|---------------|-----------| | Factor V Leiden | ~1–5% (most common) | 5–7× (hetero); 80× (homo) | Resistance to APC | | Prothrombin G20210A | Rare in Indians | 2–3× | ↑ Factor II levels | | Protein C deficiency | <0.5% | 6–8× | ↓ Natural anticoagulant | | Antithrombin III deficiency | <0.1% | 10–25× | ↓ Thrombin inhibition | **Clinical Pearl:** While Prothrombin G20210A mutation is the second most common inherited thrombophilia in Caucasians, it is **rare in South Asian (Indian) populations**. Factor V Leiden, though less prevalent in Indians than in Caucasians, remains the single most common inherited thrombophilic defect identified in Indian thrombophilia studies (Ghosh et al., Indian J Hematol Blood Transfus; Aggarwal et al., Thromb Res). ## Why Factor V Leiden is the Answer 1. **Epidemiology:** Multiple Indian cohort studies (including those from AIIMS and CMC Vellore) identify FVL as the most prevalent inherited thrombophilia in Indian patients with DVT/PE. 2. **Mechanism:** APC resistance — Factor Va is not cleaved at Arg506, prolonging its procoagulant activity. 3. **Detection:** Activated Protein C resistance assay (functional) confirmed by PCR-based genetic testing for G1691A mutation. 4. **Global context:** FVL is the most common inherited thrombophilia worldwide; Prothrombin G20210A is second most common in Caucasians but is distinctly rare in Indian, African, and East Asian populations. **Reference:** Harrison's Principles of Internal Medicine, 21st ed., Chapter on Thrombotic Disorders; Robbins & Cotran Pathologic Basis of Disease, 10th ed., Chapter on Hemostasis and Thrombosis.