Absolute Risk Of Venous And Arterial Thrombo-embolism In Thrombophilic Families Is Not Increased By High Thrombin-activatable Fibrino-lysis Inhibitor (tafi) Levels

摘要

Upon activation by the thrombin/thrombomodulin complex and/or plasmin, activated TAFI (TAFIa) inhibits the amplification of plasmin production by removing the newly exposed C-terminal lysine residues from partially degraded fibrin, thus preventing plasminogen from effectively binding to fibrin, a critical step for fibrinolysis. Since TAFIa inhibits fibrinolysis, high plasma levels of TAFI may promote the development of thrombosis. However, results from previous studies are conflicting: of six studies, four reported an association of first or recurrent venous throm-boembolism with high TAFI levels while two studies did not. The results of studies concerning the arterial side of the vasculature were also not consistent. The study briefly reviewed here assessed the absolute risk of venous and arterial thromboembolism in subjects with high TAFI levels (> 126 U/dl; normal range from 19 - 126 U/dl) and the contribution of concomitant thrombophilic defects. Relatives from four identical cohort studies in families either with deficiencies of antithrombin, protein C, protein S, hyperhomocysteinemia, high factor VIII levels, or prothrombin polymorphism G20210A and the factor V Leiden mutation were pooled for analysis. Of 1,940 relatives 187 had high TAFI levels. Annual incidences of venous thromboembolism in both relatives with high TAFI levels (0.23%) and relatives with normal TAFI levels (0.26%) were comparable to the annual incidence in the normal population (0.1 - 0.3%). However, only high factor VIII levels were associated with an increased risk of venous and/or arterial thrombosis independent of TAFI levels. None of the concomitant prothrombotic risk factors showed interactions with high TAFI levels.