Increased thrombin-activatable fibrinolysis inhibitor and decreased tissue factor pathway inhibitor in patients with hyperthyroidism

Various abnormalities of coagulation-fibrinolytic system have been reported in patients with thyroid dysfunction. Several studies indicate that coagulation and fibrinolytic system is disturbed in the patients with hyperthyroidism. The levels of plasma thrombin-activatable fibrinolysis inhibitor (TAFI) antigen and tissue factor pathway inhibitor (TFPI) have been very rarely investigated in patients with hyperthyroidism. Therefore, the main purpose of this study was to evaluate the profile of coagulation and fibrinolytic parameters including TAFI and TFPI in patients with hyperthyroidism. We also investigated the relationships between serum thyroid hormones and hemostatic parameters in these patients. Thirty patients with untreated hyperthyroidism and 25 age- and sex-matched healthy controls were included in the study. Factor V (FV), protein C, protein S, TFPI, and TAFI were measured. The relationships between serum thyroid hormones and these hemostatic parameters were examined. Compared with the control subjects, TAFI Ag levels were increased significantly in patients with hyperthyroidism [mean +/- A SD (ranges)] [177.03 +/- A 20.37 (131-206%) versus 145.9 +/- A 23.0 (89-169%)] (P < 0.001), whereas FV [89.8 +/- A 21.02 (49-124%) versus 116.1 +/- A 31.4 (56.4-200%)], protein C [72.8 +/- A 46.22 (2-149%) versus 144.0 +/- A 26.3 (74-158%)] and protein S [60.06 +/- A 42.82 (9-156%) versus 151 +/- A 33 (76-231%)] activities and TFPI Ag levels [69.56 +/- A 17.63 (39-140 ng/ml) versus 87.5 +/- A 15.9 (64-121 ng/ml)] were decreased significantly (P < 0.001 for all of them). We did not find a significant difference between Graves' disease and toxic nodular goiter for hemostatic parameters. In patients with Graves' disease, serum-free T-3 levels were inversely correlated with TFPI Ag levels (r: -0.57, P < 0.05). In conclusion, we found some important differences in the hemostatic parameters between the patients with hyperthyroidism and healthy controls. Increased TAFI and decreased FV, protein C, protein S, and TFPI in these patients represent a potential hypercoagulable and hypofibrinolytic state, which might augment the risk for atherosclerotic and atherothrombotic complications. Thus, disturbances of the hemostatic system may contribute to the excess mortality due to cardiovascular disease seen in patients with hyperthyroidism.