Blood coagulation and fibrinolysis in patients with Cushing's syndrome: increased plasminogen activator inhibitor-1, decreased tissue factor pathway inhibitor, and unchanged thrombin-activatable fibrinolysis inhibitor levels

Abstract

Background and objectives: Cushing's syndrome (CS) is associated with an increased cardiovascular mortality and morbidity. Chronic endogenous and exogenous hypercortisolism frequently induce a hypercoagulable and thrombotic condition. Little is known about hemostatic features of patients with CS. To our knowledge, plasma tissue factor pathway inhibitor (TFPI) and thrombin-activatable fibrinolysis inhibitor (TAFI) levels in these patients have not been investigated. Therefore, the main purpose of this study was to evaluate the markers of endogenous coagulation/fibrinolysis, including TFPI and TAFI, and to investigate the relationships between cortisol and these hemostatic parameters and serum lipid profile in patients with CS.

Design and methods: Twenty-four patients with CS and 24 age-matched healthy controls were included in the study. Prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, factors V, VII, VIII, IX, and X activities, von Willebrand factor (vWF), antithrombin III (AT III), protein C, protein S, tissue plasminogen activator (t-PA), tissue plasminogen activator inhibitor-1 (PAI-1), TFPI and TAFI, as well as common lipid variables, were measured. The relationships between serum cortisol and these hemostatic parameters were examined.

Results: Compared with the control subjects, platelet count, PT, fibrinogen, AT-III and PAI-1 were significantly increased in patients with CS (p<0.05, p<0.0001, p<0.01, p<0.05, and p<0.0001, respectively), whereas aPTT and TFPI levels were significantly decreased (p<0.0001 and p<0.01, respectively). Plasma TAFI Ag levels did not significantly change in patients with CS compared with the controls. In patients with CS, we showed a negative correlation between serum cortisol: 08:00 h and aPTT (r:-0.469, p<0.05). Serum cortisol: 24:00 h was positively correlated with PAI-1 Ag levels (r: 0.479, p<0.05).

Interpretation and conclusions: In conclusion, we found some important differences in the hemostatic parameters between the patients with CS and healthy controls. Increased platelet count, fibrinogen, PAI-1, and decreased TFPI levels in these patients represent a potential hypercoagulable and hypofibrinolytic state, which might augment the risk for atherosclerotic and atherothrombotic complications. This condition may contribute to the excess of mortality due to cardiovascular disease seen in patients with CS.