Abstract
<title>Abstract</title> <p>Objective To evaluate the efficacy and safety of recombinant human thrombopoietin (rhTPO), thrombopoietin receptor agonists (TPO-RAs), and their combination in pregnant patients with refractory severe immune thrombocytopenia (ITP) (platelet count < 30×10⁹/L,unresponsive to first-line corticosteroids/intravenous immunoglobulin [IVIG]). Methods This retrospective study enrolled 28 pregnant patients with severe ITP. Patients were assigned to three groups: rhTPO monotherapy (n = 16), TPO-RA monotherapy (eltrombopag, hetrombopag, or avatrombopag; n = 3), or combined rhTPO + TPO-RA therapy (n = 9). Efficacy (complete/partial/no response) was assessed 2 weeks post-treatment per standardized criteria. Safety (maternal adverse events, neonatal outcomes) and obstetric outcomes (gestational age at delivery, mode of delivery, postpartum hemorrhage) were analyzed. Results TPO-RA monotherapy achieved a 100% response rate (1 CR, 2 PR); rhTPO monotherapy had a 25% response rate (2 CR, 2 PR); combined therapy showed 0% response. No serious maternal adverse events occurred except 1 case of mild eltrombopag-related liver function impairment (resolved after switching to hetrombopag). Excluding 3 second-trimester medical inductions for treatment failure, 25 singleton live births were recorded, with only 1 neonate having thrombocytopenia (no severe neonatal complications). Conclusion TPO-RAs exhibit a favorable safety profile and promising efficacy in patients with refractory severe ITP, whereas rhTPO demonstrates a suboptimal response. Combined rhTPO + TPO-RAs therapy showed no responses, likely due to selection bias; thus, it is not routinely recommended, and sequential therapy (e.g., TPO-RA after rhTPO failure) may be a more rational approach. This study provides valuable insights for clinical decision-making in the absence of standardized second-line guidelines for gestational ITP, though large multicenter validation is needed.</p>