Hypercoagulability in Cushing's syndrome: prevalence, pathogenesis and treatment

Cushing's syndrome is not only accompanied by an increased prevalence of cardiovascular disease but also by a hypercoagulable state that is reflected by an increased incidence of venous thromboembolism. Overall, patients with CS have been reported to have a more than 10-fold increased risk of developing venous thromboembolism. Moreover, the incidence of postoperative thrombosis has been shown to be comparable to the risk after major orthopaedic surgery. Hypercoagulability in CS is due to both increased production of procoagulant factors with activation of the coagulation cascade and an impaired fibrinolytic capacity, resulting in a shortened activated partial thromboplastin time and an increased clot lysis time respectively. Although these abnormalities seem to improve 1year following successful surgery, they do not yet normalize. Therefore, sustained biochemical remission might be required to fully resolve the hypercoagulable state in CS. Considering the risk of venous thromboembolism in uncontrolled CS there may be a rationale to give patients with active CS thromboprophylaxis. So far this seems warranted following surgical interventions. However, further studies are needed to determine the optimal dosage and duration of thromboprophylaxis.