*Corresponding author: Yiren Hu (email: yirenhu@hotmail.com)
Department of General Surgery
The Third Clinical Institute Affiliated to Wenzhou Medical University
Wenzhou People's Hospital
Wenzhou 325005
China
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BJS, https://doi.org/10.1093/bjs/znae325, published 24 February 2025
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Dear Editor
We read the trial by Xie et al. evaluating enoxaparin for thromboprophylaxis after deceased-donor liver transplantation (DDLT)1. While enoxaparin increased bleeding (35.5% versus 25.5%, P=0.020) without reducing overall thrombosis, there was a striking 56% reduction in deep vein thrombosis (DVT) among patients with hepatocellular carcinoma (HCC) in subgroup analysis (HR 0.44, P=0.016). This benefit contrasts sharply with patients who did not have HCC (HR 1.02, P=0.954)1, underscoring the need for precision thromboprophylaxis.
The hypercoagulable state in patients with HCC is driven by tumour-derived tissue factor (TF) and procoagulant mucins, and creates a biological niche where enoxaparin’s anti-Xa activity directly counteracts thrombin generation2. Patients with HCC in this study experienced no significant rise in bleeding (29.8% vs. 21.8%, P=0.169)1, suggesting a favourable risk-benefit profile. In contrast overall, enoxaparin failed to reduce portal vein thrombosis (PVT) (3.5% versus 3.0%, P=0.793)1, likely due to surgical/anatomical factors (for example, anastomotic stenosis) or flow-related (for example, splenic steal syndrome) phenomena unmodifiable by pharmacological prophylaxis3.
Patients undergoing liver transplantation for reasons other than HCC are predominantly cirrhotic (median MELD 16, platelets 61,000/μl)1, and exhibit a coagulation system vulnerable to thrombosis and bleeding4, limiting enoxaparin’s efficacy.
The 7-day prophylaxis window1 may also underestimate enoxaparin’s potential, as thrombotic risks persist post-transplant. Extended prophylaxis (for example, 30 days) could enhance outcomes5. Future studies should stratify by indication for liver transplant, potentially evaluating enoxaparin or direct oral anticoagulants in HCC versus mechanical prophylaxis in non-HCC cohorts.
References
Xie K, Yang H, Wang S, Xiao C, Lan T, Jiang H, Li S et al. Comparing the efficacy and safety of thromboprophylaxis with enoxaparin versus normal saline after liver transplantation: randomized clinical trial. BJS 2025; 112, doi: https://doi.org/10.1093/bjs/znae325.
Lyman GH, Carrier M, Ay C, Di Nisio M, Hicks LK, Khorana AA et al. American Society of Hematology 2021 guidelines for management of venous thromboembolism: prevention and treatment in patients with cancer. Blood Advances 2021;5:927-974.
Intagliata NM, Caldwell SH, Tripodi A. Diagnosis, Development, and Treatment of Portal Vein Thrombosis in Patients With and Without Cirrhosis. Gastroenterology 2019;156:1582-1599.e1581.
Northup PG, Garcia-Pagan JC. Vascular Liver Disorders, Portal Vein Thrombosis, and Procedural Bleeding in Patients With Liver Disease: 2020 Practice Guidance by the American Association for the Study of Liver Diseases 2021;73:366-413.
Barkoudah E, Piazza G, Hecht TEH, Grant P, Deitelzweig S, Fang MC et al. Extended Venous Thromboembolism Prophylaxis in Medically Ill Patients: An NATF Anticoagulation Action Initiative. The American journal of medicine 2020, 133 Suppl 1: 1-27.
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