Thrombin-Activatable Fibrinolysis Inhibitor (TAFI) Antigen and Activity Assay in Patients With Primary Hypothyroidism

Abstract

Hypothyroidism causes a tendency for cardiovascular diseases. It was recently shown that thrombin-activatable fibrinolysis inhibitor (TAFI) attenuates fibrinolysis and also fibrin-plasminogen interaction by the removal of lysine and arginine residues from fibrin monomers. The aim of this study was to determine the effects of overt hypothyroidism on the levels of TAFI antigen (TAFI Ag) and TAFI activity (TAFIa). Thirty-one overt primary hypothyroid patients and age- and gender-matched 25 healthy controls were enrolled in the study. Patients were treated with L-thyroxine after the collection of blood samples. Thyroid functions were reevaluated following the achievement of euthyroid status. Thrombin-activatable fibrinolysis inhibitor Ag, tissue plasminogen activator (t-PA), and plasminogen activator inhibitor 1 (PAI-1) levels were measured with the enzyme-linked immunosorbent assay (ELISA). Thrombin-activatable fibrinolysis inhibitor activity was assessed with the chromogenic assay. Thrombin-activatable fibrinolysis inhibitor Ag (1.63% + or - 0.42% vs 1.32% + or - 0.36%, P < .01) and TAFIa (14.2 + or - 4.12 vs 11.6 + or - 3.49 microg/mL, P < .05) levels were elevated in hypothyroid patient compared to controls. Plasminogen activator inhibitor 1 and t-PA levels were not significantly different between both groups. In hypothyroid patients, TAFI Ag levels were correlated with free T(4) (r = -.373, P < .05) and thyroid-stimulating hormone (TSH) levels (r = .748, P < .001). Regression analysis showed that TSH levels were predictors of TAFI Ag levels (P < .001, beta =.671, 95% confidence interval [CI]: 0.008-0.017). Following L-thyroxine treatment, TAFI Ag (1.63% + or - 0.42%, 1.34% + or - 0.33%, P < .05) and TAFIa (14.2 + or - 4.12 microg/mL, 12.0 + or - 2.77 microg/mL, P < .05) levels were significantly decreased, but t-PA and PAI-1 levels remained unchanged. This results point out that the fibrinolytic activity was decreased in hypothyroid patients, and therefore the achievement of euthyroid status is important in ameliorating the increased risk of cardiovascular disease.

Hemostasis in Hypothyroidism and Autoimmune Thyroid Disorders

“…This process results in less plasmin formation. TAFI attenuates the fibrinolytic system by inhibiting the binding of plasminogen to fibrin and attenuation of fibrin-plasminogen interaction that causes inhibition of fibrinolysis and a tendency to thrombosis ( 59 - 62 ). The elevation of TAFI antigen is a cause of hypofibrinolysis in several endocrinological disorders ( 63 , 64 ).…”

“…PAI-1 and t-pA, however, were similar between two groups. The authors believe that fibrinolytic activity substantially decreases when hypothyroidism gets more severe and thyroid hormone therapy to restore euthyroidism may be important in ameliorating the increased risk of cardiovascular events ( 62 ).…”

Metabolic Profiling Provides a System Understanding of Hypothyroidism in Rats and Its Application

“…Therefore, inadequate thyroid hormone has widespread consequences for the body. Some studies have shown that hypothyroidism may induce delayed skeletal development [3], cardiovascular diseases [4], secondary hypertension [5], deterioration of human reproductive health [6], and changes in the brain structure and function [7].…”

New Insights into Subclinical Hypothyroidism and Cardiovascular Risk

“…Very recently, it was reported that in hypothyroidism the thrombin-activated fibrinolysis inhibitor (TAFI), which attenuates fibrinolysis and lowers fibrin-plasminogen interaction by the removal of lysine-arginine residues from fibrin monomers, and TAFI antigen are increased. 70 These results suggest that fibrinolytic activity is decreased in hypothyroidism. Decreased fibrinolytic activity, expressed by lower D-dimer levels, higher a2 antiplasmin activity, and increased levels of tissue plasminogen activator inhibitor antigen, was reported in patients with progressive moderate to severe hypothyroidism.…”