Significant Variability in Postoperative Thromboprophylaxis in Cushing's Disease Patients: A Survey of the North American Skull Base Society and the AANS/CNS Joint Tumor Section

Abstract

Introduction Cushing's disease (CD) is associated with hypercoagulability which is associated with an increased risk of venous thromboembolic events (VTEs) perioperatively. This risk persists even after successful transsphenoidal surgery (TSS). However, there are no current guidelines for pharmacologic thromboprophylaxis in this patient population.

Objective Characterize existing thromboprophylaxis management practices in patients undergoing TSS for CD.

Methods An anonymous RedCap survey comprised of questions about perioperative thromboprophylaxis in CD patients was distributed via the American Association of Neurological Surgeons (AANS)/Congress of Neurological Surgeons (CNS) Joint Tumor Section and the North American Skull Base Society (NASBS) email lists.

Results The survey was distributed to 554 members of the AANS/CNS Joint Tumor Section and 1,094 members of NASBS asking that members who surgically treat CD respond. Sixty responses (3.0% response rate) were received. Fifty-two (86.7%) respondents are involved in the postoperative management of CD patients. Thirty-six (69.2%) treat all patients with postoperative VTE chemoprophylaxis, 8 (15.4%) treat some patients, while 8 (15.4%) do not use chemoprophylaxis. Preferred chemoprophylaxis varies as 26 (59.1%) administer low molecular weight heparin, 14 (31.8%) give unfractionated heparin, 1 (2.3%) give direct oral anticoagulants, and 3 (6.8%) give aspirin. Most (28, 53.8%) of the respondents perceive the VTE risk in this patient population to be 0 to 5%, 16 (30.8%) perceive the risk to be 6 to 10%, and 8 (15.4%) perceive it to be 11 to 20%.

Conclusion There is great variability in VTE detection and postoperative prevention practice patterns in CD patients. This study highlights the need for prospective studies to clarify optimal pharmacologic chemoprophylaxis strategies and duration in this patient population.

Keywords

venous thromboembolic events - chemoprophylaxis - pituitary adenoma - ACTH-secreting - deep vein thrombosis - pulmonary embolism

Publication History

Received: 07 April 2023

Accepted: 17 July 2023

Article published online:
29 August 2023

• References

• 1 Isidori AM, Minnetti M, Sbardella E, Graziadio C, Grossman AB. Mechanisms in endocrinology: the spectrum of haemostatic abnormalities in glucocorticoid excess and defect. Eur J Endocrinol 2015; 173 (03) R101-R113
• 2 Soni P, Koech H, Silva D. et al. Cerebral venous sinus thrombosis after transsphenoidal resection: a rare complication of Cushing disease-associated hypercoagulability. World Neurosurg 2020; 134: 86-89
• 3 Boscaro M, Sonino N, Scarda A. et al. Anticoagulant prophylaxis markedly reduces thromboembolic complications in Cushing's syndrome. J Clin Endocrinol Metab 2002; 87 (08) 3662-3666
• 4 Wagner J, Langlois F, Lim DST, McCartney S, Fleseriu M. Hypercoagulability and risk of venous thromboembolic events in endogenous Cushing's syndrome: a systematic meta-analysis. Front Endocrinol (Lausanne) 2019; 9: 805
• 5 Kastelan D, Dusek T, Kraljevic I, Aganovic I. Hypercoagulable state in Cushing's syndrome is reversible following remission. Clin Endocrinol (Oxf) 2013; 78 (01) 102-106
• 6 Erem C, Nuhoglu I, Yilmaz M. et al. Blood coagulation and fibrinolysis in patients with Cushing's syndrome: increased plasminogen activator inhibitor-1, decreased tissue factor pathway inhibitor, and unchanged thrombin-activatable fibrinolysis inhibitor levels. J Endocrinol Invest 2009; 32 (02) 169-174
• 7 Sabahi M, Shahbazi T, Maroufi SF. et al. MRI-negative Cushing's disease: a review on therapeutic management. World Neurosurg 2022; 162: 126-137.e1
• 8 Abbassy M, Kshettry VR, Hamrahian AH. et al. Surgical management of recurrent Cushing's disease in pregnancy: a case report. Surg Neurol Int 2015; 6 (Suppl. 25) S640-S645
• 9 Miljic P, Miljic D, Cain JW, Korbonits M, Popovic V. Pathogenesis of vascular complications in Cushing's syndrome. Hormones (Athens) 2012; 11 (01) 21-30
• 10 Barbot M, Daidone V, Zilio M. et al. Perioperative thromboprophylaxis in Cushing's disease: what we did and what we are doing?. Pituitary 2015; 18 (04) 487-493
• 11 McCormick JP, Sun M, Shafqat I, Heaney AP, Bergsneider M, Wang MB. Venous thromboembolic (VTE) prophylaxis in Cushing disease patients undergoing transsphenoidal surgery. Interdiscip Neurosurg 2022; 27 (09) 101371
• 12 Fleseriu M, Auchus R, Bancos I. et al. Consensus on diagnosis and management of Cushing's disease: a guideline update. Lancet Diabetes Endocrinol 2021; 9 (12) 847-875
• 13 Garcia DA, Baglin TP, Weitz JI, Samama MM. Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141 (02) e24S-e43S
• 14 Ceccato D, Di Vincenzo A, Pagano C, Pesavento R, Prandoni P, Vettor R. Weight-adjusted versus fixed dose heparin thromboprophylaxis in hospitalized obese patients: a systematic review and meta-analysis. Eur J Intern Med 2021; 88: 73-80
• 15 Arnold MA, Revuelta Barbero JM, Pradilla G, Wise SK. Pituitary gland surgical emergencies: the role of endoscopic intervention. Otolaryngol Clin North Am 2022; 55 (02) 397-410
• 16 Al-Qurayshi Z, Bennion DM, Greenlee JDW, Graham SM. Endoscopic pituitary surgery: national database review. Head Neck 2022; 44 (12) 2678-2685
• 17 Agam MS, Wedemeyer MA, Wrobel B, Weiss MH, Carmichael JD, Zada G. Complications associated with microscopic and endoscopic transsphenoidal pituitary surgery: experience of 1153 consecutive cases treated at a single tertiary care pituitary center. J Neurosurg 2018; 130 (05) 1-8
• 18 Rutland JW, Dullea JT, Oermann EK. et al. Post-operative vision loss: analysis of 587 patients undergoing endoscopic surgery for pituitary macroadenoma. Br J Neurosurg 2022; 36 (04) 494-500
• 19 Younus I, Gerges MM, Godil SS. et al. Incidence and risk factors associated with reoperation for sellar hematoma following endoscopic transsphenoidal pituitary surgery. J Neurosurg 2019; 133 (03) 1-7
• 20 Waqar M, Chadwick A, Kersey J. et al. Venous thromboembolism chemical prophylaxis after endoscopic trans-sphenoidal pituitary surgery. Pituitary 2022; 25 (02) 267-274
• 21 Ostrom QT, Cioffi G, Gittleman H. et al. CBTRUS Statistical Report: primary brain and other central nervous system tumors diagnosed in the United States in 2012-2016. Neuro-oncol 2019; 21 (Suppl. 05) v1-v100
• 22 Daly AF, Beckers A. The epidemiology of pituitary adenomas. Endocrinol Metab Clin North Am 2020; 49 (03) 347-355
• 23 Barker II FG, Klibanski A, Swearingen B. Transsphenoidal surgery for pituitary tumors in the United States, 1996-2000: mortality, morbidity, and the effects of hospital and surgeon volume. J Clin Endocrinol Metab 2003; 88 (10) 4709-4719