Risk of Venous Thromboembolism Is Not Increased by Elevated TAFI Levels.

Abstract

TAFI (Thrombin-activatable fibrinolysis inhibitor) is a suppressor of fibrinolysis and high plasma levels of TAFI are assumed to induce venous thromboembolism (VTE). A few studies published on this subject identified TAFI as a mild risk factor for VTE. The risk may be increased if high TAFI levels are combined with other trombophilic defects. We performed a retrospective study to asses the absolute risk of VTE associated with elevated levels of TAFI and the contribution of concomitant thrombophilic defects. Subjects were recruited from a previous large family cohort study, which was designed to estimate the risk of VTE in first degree relatives of probands with documented VTE and a hereditary deficiency of antithrombin, protein C or protein S. Probands were excluded from analysis. Blood samples of relatives were tested on deficiencies of antithrombin, protein C and protein S, prothrombin G20210A, factor FV Leiden, hyperhomocysteinemia and increased levels of factor VIII:C, IX:C and XI:C. TAFI activity was additional measured by chromogenic assay on plasma samples stored at minus 80 degrees Celsius.We analysed 350 of 457 relatives, who were tested on TAFI. TAFI levels observed in women were lower than in men (median 97 versus 106 U/dL) and increased with age (median from 95 U/dL at age 15–30 yr to 107 U/dL at age>60 yr). Relatives with TAFI levels above the 90th percentile (>128 U/dL) had the same absolute risk of VTE as relatives with TAFI levels below the 90th percentile. Annual incidences (AI) were 0.74 versus 0.72 % per year: relative risk (RR) 1.0; 95% CI.0.51–2.10 (Table).Concomitant thrombophilic defects were demonstrated in 82% of the relatives. These defects were equally distributed among relatives with TAFI levels of >90th versus <90th percentile. Relatives with TAFI levels above the 90th percentile and concomitance of at least one other thrombophilic defect were not at increased risk of VTE compared to relatives with lower TAFI levels and concomitant thrombophilic defects (RR 0.83; 95% CI 0.41–1.68).Our data do not support that eleveated TAFI levels are a risk factor for VTE. The high absolute risk of VTE among relatives is mainly due to the presence of other thrombophilic defects rather than elevated TAFI levels, as interactions between TAFI and other thrombophilic defects were not demonstrated.VTE (n)Observation yearsAI (95% CI)RR (95% CI)TAFI > 90th percentile912090.74 (0.3–1.4)1.0 (0.51–2.10)Concomitance911470.78 (0.4–14.9)0.83 (0.41–1.68)No concomitance0620TAFI < 90th percentile5373640.72 (0.5–0.9)RefConcomitance5357240.93 (0.7–1.2)RefNo concomitance014260