A Prospective Study to Assess the Absolute Incidence of Venous Thromboembolism (VTE) Associated with Hereditary Deficiencies of Protein C, Protein S and Antithrombin and the Contribution of Cosegregation of Other Thrombophilic Defects

Abstract number: P0066

Brouwer JLP, Ten Kate MK, Veeger NJGM, Van der Schaaf W, Kluin-Nelemans HC, Van der Meer J

Hereditary deficiencies of protein C (PC), protein S type I (PS) and antithrombin (AT) are strong risk factors for VTE, as demonstrated in retrospective studies. We performed a prospective study to estimate the absolute risk of VTE for these deficiencies and the contribution of cosegregation. From a large family cohort study (DESCARTES, 468 relatives of 91 symptomatic, deficient probands), 149 asymptomatic deficient relatives and 233 asymptomatic non-deficient relatives were enrolled. Deficiency was confirmed by repeated measurements, its inheritance by a deficiency in at least 2 family members. Cosegregating thrombophilic disorders contained factor V Leiden, prothrombin G20210A mutation, high levels of FVIII:C, FIX:C and FXI:C, hyperhomocysteinemia. Thromboprophylaxis was restricted to high risk situations, like surgery. Oral contraceptives were discouraged in deficient relatives. VTE was objectively diagnosed. Annual incidences (AI) of VTE were calculated. The total number of observation years was 2529. VTE occurred in 16/149 deficient relatives (11%), 7 events were secondary to external risk factors (despite thromboprophylaxis). In 5/233 non-deficient relatives (2%), VTE was demonstrated, in all cases after surgery. Results are shown in the table. Cosegregation (CO) was demonstrated in 58% of relatives.

The absolute risk estimates in this prospective study are comparable to those in previous retrospective studies and are influenced by cosegregation.