Research PapersThe A20210 allele in the prothrombin gene enhances the risk of venous thrombosis in carriers of inherited protein S deficiencyCastaman, G.; Tosetto, A.; Cappellari, A.; Ruggeri, M.; Rodeghiero, F.Author Information The authors are with the Department of Hematology and Hemophilia and Thrombosis Center, San Bortolo Hospital, Vicenza, Italy. Received 15 November 1999; accepted 21 January 2000 Address correspondence to: Giancarlo Castaman, Department of Hematology, San Bortolo Hospital, I-36100 Vicenza, Italy. Tel: (+39) 444 993 679; fax: (+39) 444 993 922; e-mail: [email protected] Blood Coagulation and Fibrinolysis: June 2000 - Volume 11 - Issue 4 - p 321-326 Buy Abstract 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. © 2000 Lippincott Williams & Wilkins, Inc.