Familial thrombophilia and the prothrombin 20210A mutation: association with increased thrombin generation and unusual thrombosis

The 20210A prothrombin mutation has recently been associated with an increa sed risk of venous thrombosis, but the mechanism of the increased thromboti c risk in affected persons has not been elucidated We report on a thromboph ilic family in which the proband presented with cerebral vein thrombosis an d homozygosity for the 20210A prothrombin mutation as her only identifiable risk factor for venous thrombosis. Extended genotyping of family members r evealed seven other affected, but asymptomatic, first-degree relatives tone A/A homozygote and six G/A heterozygotes). Plasma levels of prothrombin, p rothrombin fragments 1+2 and thrombin-antithrombin complexes were highest i n A/A homozygotes, intermediate in G/A heterozygotes and lowest in those wi th the G/G homozygous normal genotype, while D-dimer levels were elevated o nly in A/A homozygotes. Our results suggest that the 20210A prothrombin mut ation is associated with activation of coagulation and increased thrombin g eneration, not only in patients with a past history of thrombosis but also in otherwise healthy asymptomatic persons. In a similar fashion to the homo zygous factor V Leiden mutation, patients with the homozygous 20210A prothr ombin mutation could be at highest risk of thrombosis, as suggested by our patient who presented with unusual thrombosis. (C) 1999 Lippincott Williams & Wilkins.