Detection of Factor V Leiden and Prothrombin Gene Mutations in Patients Who Died With Thrombotic Events

Abstract

Context.—Individuals with factor V or prothrombin gene mutations are at increased risk for thrombotic events. Furthermore, the risk of recurrent deep venous thrombosis in heterozygous carriers of both factor V Leiden and prothrombin gene mutations is high enough that some investigators suggest lifelong warfarin prophylaxis for these individuals, even with a single spontaneous thrombotic event. Objectives.—To assess the incidence of factor V Leiden and prothrombin gene mutations in an autopsy population and to determine if these tests can prove useful in identification of at-risk family members. Design.—We analyzed factor V Leiden and prothrombin gene mutations in 45 patients who died with or of thrombotic events, using archival tissue and multiplex allele-specific polymerase chain reaction amplification. The wild-type factor V gene was amplified in all 45 patients, whereas the wild-type prothrombin gene was amplified in 29 patients. Results.—Two patients (4.4%) who died with thrombotic events at the ages of 35 and 92 years were heterozygous for factor V gene mutation. Two additional patients (6.7%), who died with thrombotic events at the ages of 26 and 39 years, were heterozygous for prothrombin gene mutation. Patients homozygous for either factor V or prothrombin gene or simultaneously heterozygous for both genes were not detected in our study. Conclusions.—Our findings suggest that screening the relatives of elderly patients who die with thrombotic events would not be cost-effective because of the low incidence of these mutations in the autopsy population. However, because the incidence of these mutations appeared significantly more frequently among individuals who died at 39 years or younger, testing the relatives of this subset of patients may prove useful for detection of at-risk individuals who would benefit from preventive anticoagulation therapy.

Hereditary Thrombophilia in Recurrent Ivf Failure

“…Thrombophilic genetic mutations increase the tendency toward coagulation and thromboembolic disease (10) . Of the two main recognized genetic mutations factor V Leiden (FVL) mutation involves a guanineto-adenine substitution (G/A) at nucleotide 1691 in exon 10, which results in synthesis of a defective factor V molecule, resistant to cleavage by activated protein C (11,12) . Sequence variation of a G to A transposition in the 3`-untranslated region of the prothrombin gene (FII; position 20210) results in increased plasma prothrombin and a two-to-four fold increased risk for thromboembolic disease (13,14) .…”