Efficacy of a Venous Thromboembolism Prophylaxis Protocol After Pituitary Surgery for Cushing's Disease

Background: The hypercoagulable state associated with Cushing’s Disease (CD) can persist postoperatively, even after remission of hypercortisolism. Venous thromboembolism (VTE) events most often occur one to three months after surgery and can result in significant morbidity and mortality. The reported incidence of postoperative VTE in CD ranges from approximately 2% to 3.4%. Despite this increased risk, there is variability in the literature on how best to prevent VTE in CD. Our study evaluates the effectiveness of a VTE prophylaxis protocol for patients undergoing endoscopic endonasal pituitary surgery for CD. Methods: We performed a retrospective chart review on patients with CD who underwent pituitary surgery between 2017 and 2024, after implementation of a VTE prophylaxis protocol. Per protocol, patients underwent a lower extremity ultrasound preoperatively, received chemoprophylaxis with subcutaneous heparin (5,000 or 7,500 units) starting the night of surgery, and were given enoxaparin 40 or 60 mg SC daily for 30 days postoperatively. Demographic, clinical, and perioperative variables were extracted from electronic health records. Outcomes included post-operative VTE events and bleeding complications, which were analyzed using descriptive statistics. Results: Eighty patients were included in the study. The median age was 43 years (IQR 31–54), the median body mass index (BMI) was 36 kg/m2 (IQR 32–42), and 64 patients (80%) were female. A prior history of VTE was present in 6 patients (7.6%), and 7 patients (8.9%) were on anticoagulants before the surgery. Sixty-one patients (76%) underwent preoperative lower-extremity ultrasound, none of which were positive. All patients underwent an endoscopic endonasal approach, with 18 (23%) undergoing a transcavernous approach and/or selective medial cavernous wall resection. Twenty-one patients (27%) received at least a single dose of desmopressin postoperatively, although only 1 (1.3%) required long-term desmopressin. Median hospital length of stay was 3 days (IQR 3–4). Inpatient prophylaxis was administered to 79 of 80 patients (98.7%), and 70 patients (89%) were discharged on enoxaparin. Postoperative VTE occurred in 3 patients (3.8%) during the index admission: 1 pulmonary embolism, and 2 peripheral inserted central catheter (PICC) associated upper extremity (UE) VTEs, both associated with prolonged use in patients who returned to the operating room for additional tumor/gland removal. No VTE events occurred within 30 days of discharge. There were no sellar or intracranial hemorrhages. Four (5.0%) patients experienced self-limited epistaxis within 30 days of discharge: one during index admission while on full anticoagulation for a PICC-associated UE VTE that resolved with bedside intervention, and three post-discharges while on prophylactic enoxaparin (two resolved upon arrival to the emergency department, and one resolved with absorbable packing in clinic). Conclusion: Implementation of a standardized VTE prophylaxis protocol in patients undergoing endoscopic endonasal surgery for CD was associated with low postoperative VTE rates, no instances of sellar/intracranial hemorrhage, and acceptable rates of minor epistaxis events. The utility of routine preoperative lower extremity screening ultrasounds remains uncertain. Future studies are necessary to refine the ideal VTE prophylaxis protocol in CD. Publication History Article published online: 27 February 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany