The A20210 allele in the prothrombin gene enhances the risk of venous thrombosis in carriers of inherited protein S deficiency

Sixteen families with inherited protein S deficiency and venous thromboembolism (VT) were screened for the presence of factor V (FV) Leiden mutation and for the G20210A allele in the prothrombin gene. While FV Leiden was not detected in any of the families, protein S deficiency and prothrombin mutation were present in five families. To assess the risk of VT in carriers of the combined defects, a total of 92 members of the 16 families, including propositi, were examined. Thirty subjects were normal 40 showed protein S deficiency, 10 the prothrombin mutation and 12 showed both abnormalities. When index cases were excluded, thrombosis history were present in 40.7% of protein S-deficient patients, 75% of patients with combined abnormality, one out of the 10 (10%) with prothrombin mutation and only one (3.3%) of the normal subjects. Relatives with combined defects showed the highest incidence rate of VT in comparison with normal relatives (rate ratio = 32.4), those with protein S deficiency an intermediate degree (rate ratio = 15.7), and G20210A relatives the lowest (rate ratio = 3.4). Relatives with combined defects had an increased risk of VT in comparison with relatives with protein S deficiency (incidence rate ratio 2.1; 95% confidence interval, 0.7-5.41; P = 0.1). In conclusion, the presence of the prothrombin mutation seems to increase the risk of VT carriers of protein S deficiency, although additional families are required to fully estimate the magnitude of risk. Blood Coagul Fibrinolysis 11:321-326 (C) 2000 Lippincott Williams & Wilkins.