Coagulopathy in Cushing’s Syndrome

Abstract

A hypercoagulable state and its consequent increased incidence of thromboembolic complications are reported in patients with Cushing’s syndrome (CS). These alterations are related to cortisol excess that induces prothrombotic changes in blood by several and complex mechanisms including increased levels of clotting factors, mainly factor VIII and von Willebrand factor (VWF) and impaired fibrinolytic capacity. However, it has recently been observed that the increase in VWF levels is not a constant feature of CS and that VWF response to glucocorticoids is genetically determined and depends on the presence of particular polymorphisms in the VWF gene promoter. The risk of venous thromboembolism is moreover enhanced in patients with CS by additional endogenous and exogenous risk factors such as obesity, bed rest, surgery and invasive diagnostic procedures like inferior petrosal sinus (IPS) sampling. In line with all these data, patients with active CS should be treated as having a prothrombotic disorder and undergo antithrombotic prophylaxis during IPS sampling. Special care should be taken in the immediate perioperative period in order to avoid thromboembolic events. In the absence of prospective randomized trials, preventive antithrombotic treatment (best with heparin) during IPS sampling and low-dose heparin treatment early after surgery should be suggested.

Mortality in Cushing's syndrome: systematic analysis of a large series with prolonged follow-up

“…The association of chronic hypercortisolaemia with a number of morbidities has been well established (e.g. central obesity, insulin resistance and abnormalities in glucose metabolism, hypertension, dyslipidaemia, hypercoagulability, osteoporosis and neuropsychiatric disorders) (1,2,3,4,5,6,7), and if left untreated it has a major negative impact on survival (8). Furthermore, even after successful treatment, a number of complications and risks may persist (1,3,4,7,9,10,11), raising concerns regarding the long-term mortality of these patients.…”

D-dimer as a significant marker of deep vein thrombosis in patients with subclinical or overt Cushing’s syndrome

“…In a hypercortisol state, an impaired hemostatic system was found to associate significantly with several biomarkers such as elevated levels of von Willebrand factor (VWF), factor VIII, factor IX, fibrinogen, and plasminogen activator inhibitor-1 (PAI-1) [4][5][6]. Recently, VWF gene promoter polymorphisms have been reported to increase the risk of VTE via elevated levels of VWF in CS patients [7].…”

Activity of selected coagulation factors in overt and subclinical hypercortisolism

“…The prothrombotic effect of this group of steroids results from their direct effect on a number of hemostasis parameters as well as from concomitant metabolic disorders. Glucocorticoids stimulate the synthesis of coagulation factors by altering various transcription factors [25][26][27]. On average the stimulatory effect is absent after 12 months following successful surgery for Cushing's syndrome [12].…”