High factor VIII levels contribute to the thrombotic risk in families withfactor V Leiden

Factor V Leiden (FVL)-carrying relatives of selected patients with venous t hromboembolism (VTE) have much higher venous thrombotic risks than FVL-carr ying relatives of unselected consecutive patients with VTE. To find an expl anation for this, we explored other risk factors of VTE, in particular the presence of high factor VDI levels, in a retrospective follow-up study. We assessed levels of factor VIII, factor IX, fibrinogen, protein C, protein S , antithrombin, the presence of prothrombin 20210A, and the occurrence of V TE in 61 first-degree relatives of 12 selected thrombophilic families harbo uring FVL, and 183 first-degree relatives of 47 unselected families of FVL carriers with a first VTE. In all families, FVL appeared to be an independe nt risk factor for VTE. Higher thrombosis incidence rates were found in car riers of both FVL and high factor VIII levels (greater than or equal to 150 IU/dl), while high levels of factor VDI appeared to be an independent thro mbotic risk factor only in selected thrombophilic families. The fraction. o f individuals with more than one prothrombotic coagulation disorder was 10% higher in selected families. These results and the higher thrombotic risks we found in the thrombophilic families favour the hypothesis that other un known coexisting genetic defects contribute to thrombophilia.