The efficacy and safety of thrombopoietin receptor agonists in patients with chronic liver disease undergoing elective procedures: a systematic review and meta-analysis

Abstract

Thrombopoietin receptor agonists (TPO-RAs) can mitigate preprocedural thrombocytopenia in patients with chronic liver disease (CLD) however their effects on procedural outcomes is unclear. In this meta-analysis, we aimed to better define the efficacy, thrombotic risk and bleeding mitigation associated with the use of preoperative TPO-RAs in patients with CLD. We performed a systematic review and meta-analysis of randomized placebo-controlled clinical trials to assess the use of preprocedural TPO-RAs in patients with CLD, searching MEDLINE, EMBASE and the Cochrane library database. Six publications comprising eight randomized trials (1229 patients; 717 received TPO-RAs, 512 received placebo) and three unique TPO-RAs were retrieved. The majority of the included procedures were endoscopic. TPO-RAs were significantly more likely to result in a preoperative platelet count greater than 50 x 10⁹/L (72.1% vs 15.6%, RR 4.8, 95% CI 3.6–6.4 p < .00001. NNT 1.8) and reduced the incidence of platelet transfusions (22.5% vs 67.8%, RR 0.33, 95% CI 0.3–0.4 p < .00001. NNT 2.2). Total periprocedural bleeding was decreased in patients who received TPO-RAs (11.6% vs 15.6%, RR 0.64, 95% CI 0.5–0.9 p = .01. NNT 24.7) and there was no increase in the rate of thrombosis (2.2% vs 1.8% RR 1.25, 95% CI 0.6–2.9 p = .60. NNH 211.1). In patients with CLD the use of preprocedural TPO-RAs resulted in significant increased platelet counts, and decreased the incidence of platelet transfusions as compared to placebo. TPO use likewise decreased the incidence of total periprocedural bleeding without increasing the rate of thrombosis.

Keywords:

• Bleeding
• procedures
• thrombopoietin

Acknowledgements

Authors of this work have been supported by grants from the National Institutes of Health, National Heart, Lung, and Blood Institute (HL101972, HL144113). H. Al-Samkari is the recipient of the National Hemophilia Foundation-Shire Clinical Fellowship Award, the Harvard KL2/Catalyst Medical Research Investigator Training Award, and the American Society of Hematology Scholar Award. J. Shatzel is supported by the National Institutes of Health, National Heart, Lung, and Blood Institute (HL151367).

Declaration Of Interest

J.J.S. is a consultant for Aronora, Inc. H.A. receives research funding to his institution from Agios and Dova and is a consultant for Agios, Dova, and Amgen. The remaining authors declare no potential conflict of interest.

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Additional information

Funding

This work was supported by the National Heart, Lung, and Blood Institute [HL151367].