Low thrombosis rate seen in blood donors and their relatives with inherited deficiencies of antithrombin and protein C: correlation with type of defect, family history, and absence of the factor V Leiden mutation.

We have previously identified a group of blood donors with inherited deficiencies of either antithrombin (AT) or protein C who appear to have a relatively low thrombosis rate. In the 5 years that have elapsed since initial identification of these individuals, resistance to activated protein C (APC resistance), which is associated with the factor V Leiden gene mutation, has emerged as an important and highly prevalent inherited thrombophilic risk factor. We have followed 28 donors/relatives with deficiency of AT (median age 48 years, range 16-77) and 23 with deficiency of protein C (median age 44 years, range 15-79) over a period of 5 years. During the study period only one individual, who was previously symptomatic, has suffered a thrombotic event which occurred spontaneously whilst on warfarin. We have now excluded coinheritance of APC resistance due to the factor V Leiden mutation in our cohort. Our findings demonstrate that individuals with single inherited thrombophilic defects are not uncommon and are frequently asymptomatic. The absence of the factor V Leiden mutation may in part explain the low thrombosis rate observed, and lends support to the hypothesis that multiple thrombophilic defects may be necessary for the development of thrombosis.