Identification of Prothrombin Belgrade Variant in a Mexican-American Family with Recurrent Deep Vein Thrombosis

A rare prothrombin variant (c.1787G > A, p.Arg596Gln), also known as the prothrombin Belgrade variant, has been associated with an increased predisposition to thrombosis through resistance to antithrombin. This variant has been previously reported in individuals from Serbia, Japan, China, and India. In this case report, we described the first reported case of heterozygosity for the prothrombin Belgrade variant in a Mexican-American family. Affected individuals had negative results on standard hypercoagulable studies; however, they exhibited a history of early-onset and recurrent venous thromboembolism (VTE). Although rare, the prothrombin Belgrade variant-and other prothrombin variants associated with antithrombin resistance-may be underrecognized in patients with recurrent thrombotic events, particularly among individuals from ethnic backgrounds not previously associated with this variant. These findings support the consideration of comprehensive genetic thrombophilia testing, including full sequencing of the prothrombin gene, in patients with negative standard hypercoagulable studies but a strong personal and/or family history of VTE.