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Systematic Review ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Endocrinol. | doi: 10.3389/fendo.2018.00805

Hypercoagulability and Risk of Venous Thromboembolic Events in Endogenous Cushing’s syndrome: A Systematic Meta-Analysis

  • 1Oregon Health & Science University, United States
  • 2Université de Sherbrooke, Canada
  • 3Singapore General Hospital, Singapore

Background: Hypercortisolism has been implicated in the development of venous thromboembolic events (VTE). We aimed to characterize VTE risk in endogenous Cushing’s syndrome (CS) patients, compare that risk to other pathologies, and determine if there are any associated coagulation factor changes.
Methods: Medline and Scopus search for “hypercortisolism” and “thromboembolic disease” from January 1980 - April 2017 to include studies that reported VTE rates and/or coagulation profile of CS patients. A systematic review and meta-analysis were performed.
Results: Forty-eight studies met inclusion criteria. There were 7,142 CS patients, average age was 42 years and 77.7% female. Odds ratio of spontaneous VTE in CS is 17.82 (95%CI 15.24-20.85, p < 0.00001) when comparing to a healthy population. For CS patients undergoing surgery, the odds ratio (both with / without anticoagulation) of spontaneous VTE is 0.26 (95%CI 0.07-0.11, p < 0.00001) / 0.34 (0.19-0.36, p < 0.00001) when compared to patients undergoing hip fracture surgery who were not treated with anticoagulants. Coagulation profiles in patients with CS showed statistically significant differences compared to controls, as reflected by increases in von Willebrand factor (180.11 vs 112.53 IU/dL, p < 0.01), as well as decreases in activated partial thromboplastin time (aPTT; 26.91 vs 30.65, p < 0.001) and factor VIII (169 vs 137 IU/dL, p < 0.05).
Conclusion: CS is associated with significantly increased VTE odds versus general population, but lower than in patients undergoing major orthopedic surgery. Although exact timing, type, and dose of anticoagulation medication remains to be established, clinicians might consider monitoring vWF, PTT, and factor VIII when evaluating CS patients and balance advantages of thromboprophylaxis with risk of bleeding.

Keywords: Venous thomboembolism, Cushing Disease, Cushing Syndrome, Hypercoaguability, Anticoagualtion

Received: 20 Sep 2018; Accepted: 21 Dec 2018.

Edited by:

Nienke Biermasz, Leiden University, Netherlands

Reviewed by:

Leila Warszawski, Instituto Estadual de Diabetes e Endocrinologia Luiz Capriglione, Brazil
Lucio Vilar, Division of Endocrinology, Hospital das Clinicas, Federal University of Pernambuco, Brazil  

Copyright: © 2018 Wagner, Langlois, Lim, McCartney and Fleseriu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Maria Fleseriu, Oregon Health & Science University, Portland, 97239, Oregon, United States,