Anticoagulant Prophylaxis Markedly Reduces Thromboembolic Complications in Cushing’s Syndrome

Abstract

A hypercoagulable state and an increased incidence of thromboembolic complications are reported in Cushing's syndrome. The hypercoagulable state is related to an increase in plasma clotting factors, especially Factor VIII and von Willebrand factor complex, and to an impairment of fibrinolytic capacity. Retrospective analysis of postoperative thromboembolic events in a large group of patients with Cushing's syndrome, including 75 patients (group 1) evaluated in the period from 1972-1981 not receiving anticoagulants, and 232 patients (group 2), evaluated in the period from 1982-2000. Patients of group 1 underwent routine hemostatic function, i.e. prothrombin time and activated partial thromboplastine time. Patients of group 2 underwent a thorough investigation as to hemostatic parameters and received prophylactic treatment with heparin and/or warfarin. Patients with Cushing's syndrome showed various abnormalities of hemostatic parameters. A significant correlation between activated partial thromboplastine time and urinary free cortisol was observed. During follow-up, 15 patients (20%; mean follow-up, 9.4 +/- 6.4 yr) of group 1 and 14 (6.0%; mean follow-up, 6.6 +/- 4.2 yr) of group 2 showed thromboembolic complications. Of these patients, eight of group 1 and one of group 2 died. Survival analysis demonstrated a significantly higher morbidity and mortality due to thromboembolic events in group 1, not receiving anticoagulant prevention, than in group 2, treated with anticoagulants in the perioperative period until cure of the disease and normalization of clotting parameters. Cushing's syndrome is associated with a hypercoagulable state. An adequate anticoagulant prophylaxis can reverse this prothrombotic state and avoid postoperative thromboembolic events.

Systemic lupus erythematosus in a multiethnic US cohort (LUMINA): XXV. Smoking, older age, disease activity, lupus anticoagulant, and glucocorticoid dose as risk factors for the occurrence of venous thrombosis in lupus patients

“…Nevertheless, thromboembolic complications have also been reported during the initial phase of glucocorticoid use for the treatment of giant cell arteritis (40). Moreover, Cushing's syndrome is often regarded as a prothrombotic condition (41), since high levels of adrenal steroids have been shown to be associated with several clotting abnormalities, including increased levels of factor VIII, von Willebrand factor, and plasminogen activator inhibitor activity, as well as with decreased fibrinolysis (41)(42)(43). Similar clotting abnormalities have been reported in patients treated with exogenous glucocorticoids (44), indicating that glucocorticoids may, in fact, increase the risk of thrombotic events in individuals with a predisposition to develop them.…”

Hemostatic abnormalities in endocrine and metabolic disorders

“…An inverse, significant correlation was also observed between APTT and 24-h urinary free cortisol excretion. Interestingly, during the follow-up, 15 patients (20%) from group 1 and 14 patients (6%) from group 2 developed venous thromboembolic complications (80). Eight of these patients in group 1 and one in group 2 died.…”

“…Eight of these patients in group 1 and one in group 2 died. Overall, survival analysis demonstrated a significantly lower mortality and morbidity for venous thromboembolism in patients in group 2, who were treated with anticoagulants in the perioperative period until cure of the endocrine disease (80). To further explore the acute effects of glucocorticoids on the coagulation system, Brotman et al performed a small controlled clinical study (81).…”

Cushing`s disease: Fibrinogen and D-dimer levels fail to normalize despite early postoperative remission — a prospective, controlled study

“…The hypercoagulable state can lead to increased incidence of thromboembolic episodes in the postoperative period or during diagnostic procedures such as inferior petrosal sinus sampling [9][10][11][12][13][14]. Boscaro et al demonstrated significantly higher thromboembolic mortality and morbidity in a group of Cushing's syndrome patients receiving no anti-thromboembolic prevention in comparison with those in a group receiving prophylactic treatment with the use of warfarin or heparin [14].…”