High risk of thrombosis recurrence in patients with homozygous and compound heterozygous factor V R506Q (Factor V Leiden) and prothrombin G20210A.

Objective: Heterozygous Factor V R506Q [Factor V Leiden (FVL)] and prothrombin G20210A (PGM), the most common inherited thrombotic disorders in the Caucasian population, confer a low-moderate risk for first venous thromboembolic (VTE) event. We investigated the thrombotic complications of rare homozygous and compound heterozygous FVL and PGM.

Methods: A cohort of patients with homozygous and compound heterozygous FVL and PGM were evaluated at a major referral center in Central Pennsylvania, USA between June 2001 and March 2019. Data including incidence of first and recurrent thrombosis, associated risk factors, family history and demographics were collected.

Results: Seventy-five patients were eligible for analysis: 47 had homozygous FVL, three had homozygous PGM, 19 had compound heterozygous FVL and PGM, five had compound homozygous FVL and heterozygous PGM, and one had compound heterozygous FVL and homozygous PGM. Fifty-nine patients experienced 111 thromboembolic events. Forty-seven percent of first thrombotic events occurred in patients without clinical or surgical conditions predisposing to thrombosis. The rate of recurrent thromboembolism was 59%. The mean time to recurrence was 8.5 years. Ninety percent of recurrent events occurred during times when patients were not treated with anticoagulation.

Conclusion: Persons with homozygous and compound heterozygous FVL and PGM are at a significantly increased risk of first unprovoked and recurrent VTE. Patients with first thromboembolic events should be considered for long-term anticoagulation.