Thrombin Activatable Fibrinolysis Inhibitor Antigen Levels Are Inversely Correlated with Plasminogen Activator Inhibitor-1 Antigen Levels in Hyperthyroid Patients

Abstract

Abstract. Both increased and decreased fibrinolytic activity have been reported in patients with hyperthyroidism. Elevated levels of plasma plasminogen activator inhibitor-1 (PAI-1) antigen have been found in hyperthyroid patients. Thrombin activatable fibrinolysis inhibitor (TAFI) is a novel plasma protein, which inhibits fibrinolysis through removal of C-terminal lysines from partially degraded fibrin. Previously, we showed that plasma TAFI antigen levels were increased in patients with overt and subclinical hypothyroidism. The aim of this study is to investigate plasma levels of TAFI and PAI-1 antigens in hyperthyroid patients. PAI-1 and TAFI antigen levels were measured in the plasma of 29 patients with hyperthyroidism (14 overt hyperthyroid and 15 subclinical hyperthyroid), and 26 healthy individuals. Although there were increased levels of PAI-1 antigen in hyperthyroid patients, plasma TAFI antigen levels were significantly lower compared to controls (80.79 ng/ml vs. 32.42 ng/ml, p = 0.000 for PAI-1; 10.42 µg/ml vs. 12.24 µg/ml, p = 0.009 for TAFI). Elevated PAI-1 antigen levels were positively correlated with free thyroid hormones, although TAFI antigen levels were in negative correlation with free thyroxine. Furthermore, an inverse correlation between PAI-1 and TAFI antigen levels was found. Our study demonstrated that TAFI antigen levels were decreased in patients with hyperthyroidism. Inverse correlation with PAI-1 suggests that the decrease in TAFI antigen levels may be due to activation of TAFI pathway. Further studies evaluating the underlying mechanisms of low TAFI antigen levels in hyperthyroidism should be undertaken.

Effect of Levothyroxine Suppression Therapy on Plasma Thrombin Activatable Fibrinolysis Inhibitor Antigen Levels in Benign Thyroid Nodules

“…LT4 suppression treatment resulted in a non-significant increase in PAI-1 antigen levels. In accordance with our previous study [12] , TAFI antigen levels were found to be decreased in patients with endogenous hyperthyroidism. Endogenous hyperthyroid patients had significantly increased PAI-1 antigen levels when compared to healthy controls.…”

“…We observed that LT4 replacement treatment effectively reduced increased TAFI antigen levels in hypothyroidism. In a more recent study, we were able to detect reduced TAFI antigen levels in hyperthyroid patients [12] . In the present study, however, we failed to show any significant decrease in TAFI antigen levels after LT4 suppression treatment for benign thyroid nodules.…”

“…Levothyroxine replacement for hypothyroidism was effective in reducing the increased levels of TAFI in hypothyroid subjects [8] . In another previous study, we found that TAFI levels were significantly reduced in hyperthyroid subjects when compared to healthy controls [12] . In this prospective study, we aimed to investigate the effect of LT4 suppression therapy (on TAFI and PAI-1 antigen levels) for benign thyroid nodules.…”

“…Of 19 hyperthyroid patients, 9 had overt and 10 had subclinical hyperthyroidism. Plasma samples in the hyperthyroid group were obtained from age-matched premenopausal women who had enrolled in our previous study [12] .…”

Hyperthyroidism is associated with shortened APTT and increased fibrinogen values in a general population of unselected outpatients

“…Several in vivo studies on the effect of overt thyroid dysfunction on blood coagulation and fibrinolytic factors suggest that a procoagulant state might be associated with hyperthyroidism, but no reliable evidence has been provided so far on the potential biological mechanism because neither temporary nor permanent thromboembolic risk factors were consistently identified throughout the studies [7][8][9][10]. Compared with control subjects, increased values of von Willebrand factor (VWF), factor VIII factor IX, antithrombin, plaminogen activator inhibitor 1 (PAI-1) and decreased values of factor X, tissue plasminogen activator (t-PA) and TAFI were observed in patients with hyperthyroidism [13][14][15]. Significantly increased serum thrombomodulin were found by Morikawa et al in patients with Graves' disease [16].…”