Co-segregation of thrombosis with the factor V Q506 mutation in an extended family with resistance to activated protein C

The activated protein C (APC) resistance phenotype results from a mutation at one of the cleavage sites of factor V by APC (Q506). We describe a large family with an APC resistance phenotype and without any other detectable coagulation defect, including eight subjects who had developed deep venous thrombosis (mean age of the first thrombosis episode 29 years; range 17-55 years). The factor V Q506 mutation was detected in the seven patients with thrombosis who could be tested and in 13 asymptomatic subjects (mean age 17 years; range 5-33 years). The APC resistance was detectable in only 10 heterozygotes among the 19 tested. These data suggest that, in affected families, the risk for the factor V Q506 mutation carriers to develop thrombosis may be very high and that factor V genotyping must be performed in patients with thrombosis even without any detectable APC resistance phenotype.