Evaluation of haemostatic and fibrinolytic markers in patients with Cushing's syndrome: a longitudinal study
Valentina Raffaelli1, Luca Manetti1, Lucia Ruocco2, Clara Giovannetti1, Maura Genovesi1, Giovanni Pellegrini2, Fausto Bogazzi1 & Enio Martino1
Patients with active Cushings syndrome (CS) have an increased coagulability and thrombotic tendency. High glucocorticoids concentrations increase plasma clotting factors, especially von Willebrand factor (vWf) and reduced fibrinolytic capacity. Thromboemobolic complications, mainly in the postsurgical phase, have been reported.
Aim of this longitudinal study was to evaluate haemostatic and fibrinolytic markers in patients with active Cushings syndrome during the activity and after the remission or the persistency of the disease.
Forty patients (32 women and 9 men) with CS were enrolled in the study: 36 were affected by ACTH-secreting pituitary adenoma and 4 by an adrenal adenoma. All patients, at the starting of the study, had an active CS. All patients were re-evaluated after 1224 months after surgery: 27 presented the remission of the disease (Group 1), 13 had persistent hypercortisolism (Group 2). Haemostatic and fibrinolytic markers were evaluated in all patients during the activity of the disease and after surgery. No patients were taking drugs to affect coagulations tests.
von Willebrand factor (P<0.0001), plasminogen activator inhibitor (PAI-1) activity (P=0.003), antithrombin III (P=0.0002) and plasminantiplasmin complex (P=0.006) were statistically different in Group 1. No differences between active and remission patients were observed in other markers (fibrinogen, prothrombin fragment 1+2, factor V, factor VII, factor IX, factor XII, activated partial thromboplastin time, thrombinantithrombin complex, plasminogen, and D-dimer). No statistical differences of haemostatic and fibrinolytic markers were observed between patients of Group 2.
The study confirms that CS is associated with a thrombophilic state and to the alteration of the fibrinolytic system. Recent studies provide evidence that polymorphisms in the vWf and PAI-1 can influence the corticosteroid-mediated transcriptional regulation of these factors. Therefore, further studies are necessary to define the modifications of coagulation cascade in hypercortisolism.