Current clinical practice for thromboprophylaxis management in patients with Cushing's syndrome across reference centers of the European Reference Network on Rare Endocrine Conditions (Endo-ERN)

Abstract

Background: Cushing's syndrome (CS) is associated with an hypercoagulable state and an increased risk of venous thromboembolism (VTE). Evidence-based guidelines on thromboprophylaxis strategies in patients with CS are currently lacking. We aimed to map the current clinical practice for thromboprophylaxis management in patients with CS across reference centers (RCs) of the European Reference Network on Rare Endocrine Conditions (Endo-ERN), which are endorsed specifically for the diagnosis and treatment of CS. Using the EU survey tool, a primary screening survey, and subsequently a secondary, more in-depth survey were developed.

Results: The majority of the RCs provided thromboprophylaxis to patients with CS (n = 23/25), although only one center had a standardized thromboprophylaxis protocol (n = 1/23). RCs most frequently started thromboprophylaxis from CS diagnosis onwards (n = 11/23), and the majority stopped thromboprophylaxis based on individual patient characteristics, rather than standardized treatment duration (n = 15/23). Factors influencing the initiation of thromboprophylaxis were 'medical history of VTE' (n = 15/23) and 'severity of hypercortisolism' (n = 15/23). Low-Molecular-Weight-Heparin was selected as the first-choice anticoagulant drug for thromboprophylaxis by all RCs (n = 23/23). Postoperatively, the majority of RCs reported 'severe immobilization' as an indication to start thromboprophylaxis in patients with CS (n = 15/25). Most RCs (n = 19/25) did not provide standardized testing for variables of hemostasis in the postoperative care of CS. Furthermore, the majority of the RCs provided preoperative medical treatment to patients with CS (n = 23/25). About half of these RCs (n = 12/23) took a previous VTE into account when starting preoperative medical treatment, and about two-thirds (n = 15/23) included 'reduction of VTE risk' as a goal of treatment.

Conclusions: There is a large practice variation regarding thromboprophylaxis management and perioperative medical treatment in patients with CS, even in Endo-ERN RCs. Randomized controlled trials are needed to establish the optimal prophylactic anticoagulant regimen, carefully balancing the increased risk of (perioperative) bleeding, and the presence of additional risk factors for thrombosis.

Keywords: Cushing’s syndrome; Endo-ERN survey; Guidelines; Hemostasis; Hypercortisolism; Thromboprophylaxis; Venous thromboembolism.

Fig. 1

European Landscape of RCs participating in MTG Pituitary and/or MTG Adrenal of Endo-ERN and responder status. Completion of both primary and secondary survey (green icons). Completion of only the primary survey or was included for analysis of only the primary survey (blue icons). Non-responder to the surveys or exclusion from analysis of both surveys (red icons). Endo-ERN The European Reference Network on Rare Endocrine Conditions, MTG main thematic group, RC reference center

Fig. 2

Proportion of responses including each factor influencing initiation of thromboprophylaxis in patients with Cushing’s syndrome (not mutually exclusive). BG blood group, CD Cushing’s disease, CS Cushing’s syndrome, VTE venous thromboembolism, vWF von Willebrand Factor

Fig. 3

Proportion of responses from each indication for the initiation of postoperative thromboprophylaxis in patients with Cushing’s syndrome (not mutually exclusive). CD Cushing’s disease, TE thromboembolic