Contribution of prothrombin 20210A allele and factor V Leiden mutation to thrombosis risk in thrombophilic families with other hemostatic deficiencies

Background and Objectives. The aims of this study were to compare the lifet ime probability of developing thrombosis in 722 relatives of 132 thrombophi lic families of symptomatic probands with recognized thrombophilic defects and to determine the prevalence of the factor V Leiden (FVL) mutation and t he 20210A allele of the prothrombin gene (PT20210A) in these families. Design and Methods. The study included 722 members belonging to 132 unrelat ed families. The propositi were patients who had been referred to our Throm bosis Unit. The families were selected through a symptomatic proband. Once a patient with a deficiency or mutation was identified, family members were screened for the same defect. Results. The prevalence of FVL and PT20210A in families with other thrombop hilic defects was higher than expected. Compared with non-deficient individ uals, the risk of venous thrombosis was increased in subjects with antithro mbin (AT), protein S (PS) and protein C (PC) deficiencies, and in carriers of FVL and PT20210A mutations. The risk of thrombosis was significantly inc reased for individuals with combined genetic defects (PC-FVL, PS-FVL, PS-PT 20210A and FVL-PT20210A). The ages at the time of 50% thrombosis-free survi val were as follows: 34 years for AT deficiency, (19 years with FVL, 21 yea rs with PT20210A), 62 years for PC deficiency (33 years with FVL, 44 years with PT20210A), 37 years for PS deficiency (24 years with FVL, 36 years wit h PT20210A), 50 years for the FVL mutation (52 years with PT20210A), and 65 years for the PT20210A mutation. As for clinical characteristics, no diffe rences were observed except for the higher frequency of oral contraceptive- related thrombosis in women who were carriers of PT20210A or FVL. Interpretation and Conclusions. Based on these results, screening for FVL a nd PT20210A mutation is recommended in patients with other thrombophilic de fects. To the best of our knowledge, this is the first family study, includ ing the PT20210A mutation, that compares genetic risk factors for thrombosi s and the lifelong probability of developing thrombosis. (C) 2001, Ferrata Storti Foundation.