Coinheritance of the HR2 haplotype in the factor V gene confers an increased risk of venous thromboembolism to carriers of factor V R506Q (Factor V leiden)

With the aim of establishing whether the HR2 haplotype in factor V affects the risk of venous thromboembolism, a retrospective multicenter cohort stud y was performed in 810 family members identified through 174 probands who s uffered from at least 1 episode of deep vein thrombosis and/or pulmonary em bolism and had an inherited defect associated with thrombophilia (antithrom bin, protein C, or protein S deficiency; factor V R506Q or prothrombin G202 10A), Fifty-eight percent (468/810) of the family members had an inherited defect and 10% (47/468) were symptomatic, The HR2 haplotype was found in as sociation with factor V R506Q more frequently in family members with venous thromboembolism (18%) than in those without (8%). Double heterozygosity fo r factor V R506Q and HR2 conferred a 3- to 4-fold increase in the relative risk of venous thromboembolism compared with factor V R506Q alone. The medi an age at fi rst event was lower when the 2 defects were associated (46 v 5 2 years). No increase in risk of venous thromboembolism could be demonstrat ed when the HR2 haplotype was associated with inherited thrombophilic defec ts other than factor V R506Q, Because both factor V R506Q and the HR2 haplo type are very frequent, the effect of their coinheritance on the risk of ve nous thromboembolism might represent a clinically relevant issue, and scree ning for HR2 in carriers of factor V R506Q should be considered. (C) 1999 b y The American Society of Hematology.