Risk of venous thromboembolism and clinical manifestations in carriers of antithrombin, protein C, protein S deficiency, or activated protein C resistance - A multicenter collaborative family study

Deficiencies of antithrombin (AT), protein C (PC) or protein S (PS), and ac tivated protein C resistance (APCR) are very well-established coagulation d efects predisposing to venous thromboembolism (VTE). We performed a retrosp ective cohort family study to assess the risk for VTE in individuals with A T, PC, or PS deficiency, or APCR. Five hundred thirteen relatives from 9 It alian centers were selected from 233 families in which the proband had had at least 1 episode of VTE. We calculated the incidence of VTE in the whole cohort and in the subgroups after stratification by age, sex, and defect. T he overall incidence of VTE (per 100 patient-years) in the group of relativ es was 0.52. It was 1.07 for AT, 0.54 for PC, 0.50 for PS, 0.30 for APCR, a nd 0.67 in the group with a double defect. The incidence was associated wit h age, but not with sex. The mean age at onset was between 30 and 40 years for all the coagulation defects. Women had the peak of incidence in the age range of 21 to 40 years, earlier than men. The lifetime risk for VTE was 4 .4 for AT versus APCR, 2.6 for AT versus PS, 2.2 for AT versus PC, 1.9 for PC versus APCR, and 1.6 for PS versus APCR. AT deficiency seems to have a h igher risk for VTE than the other genetic defects. There is a relation betw een age and occurrence of thrombosis for both men and women. The latter had the peak of incidence earlier than the former.