Effectiveness of Recombinant Human Thrombopoietin in combination with or without Avatrombopag in Critically Ill Patients with Sepsis-Associated Thrombocytopenia

Background This study aimed to determine the effectiveness of recombinant human thrombopoietin (rhTPO) monotherapy and rhTPO combined with avatrombopag in achieving early platelet recovery (defined as a ≥ 30% increase or an absolute increase of ≥ 100 × 10⁹/L within 7 days) in critically ill patients with sepsis-associated thrombocytopenia. Methods This single-center, retrospective, case–control study was carried out between November 2022 and November 2024. The study enrolled adult patients diagnosed according to the Sepsis-3 criteria with platelet counts < 100 × 10⁹/L. Participants were treated with either rhTPO monotherapy or rhTPO in combination with avatrombopag. Baseline data were collected, including demographics, clinical assessments, and laboratory results. Statistical comparisons between groups were made using logistic regression, with P < 0.05 considered significant. A linear mixed-effects model was used for sensitivity analysis of platelet changes over time. Results A total of 217 patients were screened, 132 of them (rhTPO monotherapy, n = 51; rhTPO + avatrombopag, n = 81) met the inclusion criteria and were analyzed. Most baseline variables were similar between the two groups, with the exception of age (median 66 vs. 68 years, p = 0.024), baseline platelet count (42 vs. 34 × 10⁹/L, p = 0.018), and Sequential Organ Failure Assessment (SOFA) score (10 vs. 12, p = 0.036). There was no statistically significant difference between the groups at day 7, with the rhTPO group’s platelet response rate being 88.2% in and the combination group’s 90.1% (p = 0.958). Multivariate logistic regression analysis identified higher SOFA scores (OR 0.70, 95% CI 0.56–0.87, p = 0.001) and lower baseline platelet counts (OR 0.96, 95% CI 0.93–1.00, p = 0.042) were independent negative predictors of treatment response. On the other hand, there was no effect of combination therapy (OR 1.85, 95% CI 0.51–6.72, p = 0.350). By using longitudinal mixed-effects modeling, it was further demonstrated that there was no significant treatment–time interaction (p = 0.957). Conclusion The combination of avatrombopag and rhTPO did not improve platelet recovery within 7 days in patients with sepsis-associated thrombocytopenia. Early platelet response was strongly influenced by disease severity and baseline platelet count rather than by treatment regimen.