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April 23, 2025, 11:43

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Bleeding is a significant complication of acute-on-chronic liver failure (ACLF), with prolonged prothrombin time and thrombocytopenia in these patients elevating the perceived risk of bleeding. We were intrigued by the manuscript by Liu et al. [1], which investigates the efficacy and safety of recombinant human thrombopoietin (rhTPO) in treating thrombocytopenia among ACLF patients. This prospective, open-label study involved 70 ACLF patients with severe thrombocytopenia, who were assigned to either an rhTPO group or a control group. The primary endpoint was the proportion of patients achieving a platelet count greater than 50 × 10^9/L by day 14. The study’s noteworthy findings indicated that rhTPO significantly increased platelet counts in ACLF patients, with a higher proportion reaching the target platelet count in the rhTPO group compared to the control group (60.7% vs. 12.0%). The study concluded that rhTPO effectively elevates platelet counts, improves liver function, and reduces bleeding events in ACLF patients with thrombocytopenia, while maintaining a favorable safety profile. These findings provide promising insights into managing thrombocytopenia in ACLF patients. While this study holds clinical significance, it also has notable limitations. Liver disease has long been recognized as a condition associated with bleeding disorders, which arise from multiple factors [2,3]. These include thrombocytopenia, low levels of coagulation factors, and decreased fibrinolytic proteins, all contributing to the coagulopathy seen in liver disease [4]. Thrombocytopenia is one of the most common hematological abnormalities and often the first abnormality detected in chronic liver disease patients [5]. While mild to moderate thrombocytopenia rarely has clinical significance due to the low likelihood of spontaneous bleeding, moderate to severe thrombocytopenia can hinder patients from receiving essential interventions, including medications and invasive procedures. Delays in procedures and the need to correct platelet abnormalities can extend hospital stays and increase overall healthcare costs [6,7]. Increasing platelet counts and achieving rebalanced hemostasis appears to be a strategy for controlling the risk of acute bleeding in ACLF patients without raising the risk of thrombosis; however, the impact on disease prognosis requires further investigation [2]. Despite indicating that increasing platelet counts and achieving rebalanced hemostasis may help control the risk of acute bleeding in ACLF patients without increasing the risk of thrombosis, further investigation is necessary to understand the impact on disease prognosis. Additionally, while serum hepatocyte growth factor and thrombopoietin (TPO) levels were measured, key coagulation-related tests were not further explored. Simply correcting thrombocytopenia does not address all facets of coagulation [8]. Furthermore, laboratory tests such as platelet aggregation and thromboelastography were not conducted. These assessments could provide a more comprehensive understanding of the extent to which the coagulopathy in ACLF patients has been addressed, rather than relying solely on platelet counts [9]. Moreover, the study's small sample size limits its statistical power and may introduce confounding factors. The analysis of results was relatively straightforward and did not adequately account for potential confounders. Consequently, the conclusions drawn should be considered preliminary. The exploratory and pilot nature of this study limits its clinical significance. Nonetheless, it remains a valuable contribution to the field, providing direction for future research and establishing a foundational basis for subsequent investigations. Currently, in addition to rhTPO, there are other treatment options available, such as oral small molecule agonists of TPO receptor like avatrombopag [10]. Further studies comparing these agents are needed to determine the optimal strategies for managing bleeding risk in ACLF patients. Overall, this research offers hope for the management of ACLF patients and points toward future investigation directions. REFERENCES 1. Liu G, Tang F, Wang T, Yan JQ, Li FH, Ha FS, Zhang X, Jing L, Liang J. Efficacy of recombinant human thrombopoietin in patients with acute-on-chronic liver failure and thrombocytopenia: A prospective, open-label study. World J Gastroenterol. 2025;31 14:105004. doi: 10.3748/wjg.v31.i14.105004. 2. Lisman T, Porte RJ. Pathogenesis, prevention, and management of bleeding and thrombosis in patients with liver diseases. Res Pract Thromb Haemost. 2017;1 2:150-161. doi: 10.1002/rth2.12028. 3. Lisman T, Leebeek FW, de Groot PG. Haemostatic abnormalities in patients with liver disease. J Hepatol. 2002;37 2:280-7. doi: 10.1016/s0168-8278(02)00199-x. 4. Stravitz RT, Ellerbe C, Durkalski V, Schilsky M, Fontana RJ, Peterseim C, Lee WM; Acute Liver Failure Study Group. Bleeding complications in acute liver failure. Hepatology. 2018;67 5:1931-1942. doi: 10.1002/hep.29694. 5. Violi F, Basili S, Raparelli V, Chowdary P, Gatt A, Burroughs AK. Patients with liver cirrhosis suffer from primary haemostatic defects? Fact or fiction? J Hepatol. 2011;55 6:1415-27. doi: 10.1016/j.jhep.2011.06.008. 6. Poordad F. Review article: thrombocytopenia in chronic liver disease. Aliment Pharmacol Ther. 2007;26 Suppl 1:5-11. doi: 10.1111/j.1365-2036.2007.03510.x. 7. Moore AH. Thrombocytopenia in Cirrhosis: A Review of Pathophysiology and Management Options. Clin Liver Dis (Hoboken). 2019;14 5:183-186. doi: 10.1002/cld.860. 8. O'Leary JG, Greenberg CS, Patton HM, Caldwell SH. AGA Clinical Practice Update: Coagulation in Cirrhosis. Gastroenterology. 2019;157 1:34-43.e1. doi: 10.1053/j.gastro.2019.03.070. 9. Biswas S, Anand A, Vaishnav M, Mehta S, Swaroop S, Aggarwal A, Arora U, Agarwal A, Elhence A, Mahapatra SJ, Agarwal S, Gunjan D, Sehgal T, Aggarwal M, Dhawan R, Gamanagatti S, Shalimar. Thromboelastography-Guided versus Standard-of-Care or On-Demand Platelet Transfusion in Patients with Cirrhosis and Thrombocytopenia Undergoing Procedures: A Randomized Controlled Trial. J Vasc Interv Radiol. 2024;35 10:1508-1518.e2. doi: 10.1016/j.jvir.2024.06.014. 10. Terrault N, Chen YC, Izumi N, Kayali Z, Mitrut P, Tak WY, Allen LF, Hassanein T. Avatrombopag Before Procedures Reduces Need for Platelet Transfusion in Patients With Chronic Liver Disease and Thrombocytopenia. Gastroenterology. 2018;155 3:705-718. doi: 10.1053/j.gastro.2018.05.025.

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