Thrombin activatable fibrinolysis inhibitor and the risk for deep vein thrombosis

Thrombin activatable fibrinolysis inhibitor (TAFI, or procarboxypeptidase B ) is the precursor of a recently described carboxypeptidase that potently a ttenuates fibrinolysis, Therefore, we hypothesized that elevated plasma TAF I levels induce a hypofibrinolytic state associated with an increased risk for venous thrombosis. To evaluate this hypothesis, we developed an electro immunoassay for TAFI antigen and used this assay to measure TAFI levels in the Leiden Thrombophilia Study, a case-control study of venous thrombosis i n 474 patients with a first deep vein thrombosis and 474 age- and sex-match ed control subjects. In 474 healthy control subjects, an increase of TAFI w ith age was observed in women but not in men. Oral contraceptive use also i ncreased the TAFI concentration. TAFI levels above the 90th percentile of t he controls (> 122 U/dL) increased the risk for thrombosis nearly 2-fold co mpared with TAFI levels below the 90th percentile (odds ratio, 1.7; 95% con fidence interval, 1.1-2.5), Adjustment for various possible confounders did not materially affect this estimate, These results indicate that elevated TAFI levels form a mild risk factor for venous thrombosis. Such levels were found in 9% of healthy controls and in 14% of patients with a first deep v ein thrombosis. Elevated TAFI levels did not enhance the thrombotic risk as sociated with factor V Leiden but may interact with high factor VIII levels . (Blood. 2000;95: 2855-2859) (C) 2000 by The American Society of Hematolog y.