目的 观察血小板生成素受体激动剂（TPO-RA）与小剂量利妥昔单抗治疗激素治疗无效或复发免疫性血小板减少症（ITP）患者疗效及对凝血功能、T淋巴细胞水平的影响。 方法 该研究为单中心回顾性研究，选取2021年3月至2025年3月南通市第一人民医院收治的80例激素治疗无效或复发ITP患者，根据治疗方法分为TPO-RA组（n = 55）、利妥昔单抗组（n = 25）。比较两组治疗效果、血小板计数、凝血功能［凝血酶原时间（PT）、活化部分凝血活酶时间（APTT）］、T淋巴细胞［调节性T细胞（Treg）、辅助性T细胞17（Th17）、Treg/Th17］及不良反应。 结果 TPO-RA组总有效率（85.45%）高于利妥昔单抗组（64.00%），起效时间短于利妥昔单抗组（P < 0.05）；治疗后TPO-RA组PLT水平较高（P < 0.05）；两组治疗后PT、APTT水平差异无统计学意义（P > 0.05）；两组治疗后Treg细胞、Treg/Th17比值均提高（P < 0.05）；治疗后TPO-RA组Treg细胞、Treg/Th17比值较高（P < 0.05）；治疗后两组Th17细胞水平差异无统计学意义（P > 0.05）；两组不良反应发生率差异无统计学意义（P > 0.05）。 结论 TPO-RA用于激素治疗无效或复发ITP患者起效时间快、疗效较好，可明显提高PLT水平、改善患者免疫功能，对PT、APTT水平影响较小、安全性良好。

Objective To compare the clinical efficacy， hematologic response kinetics， immunomodulatory effects， and safety profile of thrombopoietin receptor agonists （TPO-RAs） versus low-dose rituximab in adult patients with immune thrombocytopenia （ITP） refractory to or relapsing after first-line corticosteroid therapy. Methods This was a single-center， retrospective cohort study conducted at our institution between March 2021 and March 2025. A total of 80 adult patients diagnosed with primary ITP who exhibited inadequate response to ≥ 4 weeks of corticosteroid therapy or experienced relapse within 3 months after tapering were enrolled. Patients were stratified into two treatment cohorts based on clinical decision-making： the TPO-RA group （n = 55）， receiving either eltrombopag or romiplostim； And the low-dose rituximab group （n = 25）， receiving 100 mg weekly for four doses. Primary endpoints included overall response rate （ORR； defined as platelet count ≥ 30 × 10?/L and at least twofold increase from baseline） and time to response. Secondary endpoints encompassed platelet count trajectories， coagulation parameters?prothrombin time （PT） and activated partial thromboplastin time （APTT）?and immunophenotyping of peripheral blood T lymphocyte subsets： regulatory T cells （Tregs）， T helper 17 cells （Th17）， and the Treg/Th17 ratio. Adverse events were systematically recorded and graded per CTCAE v5.0. Results The TPO-RA group achieved a significantly higher overall response rate （85.5% vs. 64.0%， P = 0.032） and shorter median time to response （14 d vs. 28 d， P < 0.001） compared with the rituximab group. Post-treatment platelet counts were markedly elevated in the TPO-RA group ［（142.6 ± 48.3） × 10?/L vs. （98.1 ± 36.7） × 10?/L， P = 0.002］. No statistically significant differences were observed in PT （P = 0.417） or APTT （P = 0.352） between groups following therapy. Both regimens significantly increased circulating Treg frequency （P < 0.001 for both） and Treg/Th17 ratio （P < 0.001 for both）； however， the TPO-RA group demonstrated greater magnitude of improvement in both parameters relative to the rituximab group （Treg： 8.2% vs. 6.1%， P = 0.018； Treg/Th17： 2.4 vs. 1.7， P = 0.023）. Th17 cell frequencies did not differ significantly between groups post-treatment （P = 0.674）. The incidence of grade ≥ 2 adverse events was comparable （12.7% vs. 16.0%， P = 0.715）. Conclusions In corticosteroid-refractory or relapsed ITP， TPO-RAs confer superior and more rapid platelet recovery compared with low-dose rituximab， accompanied by more pronounced restoration of Treg-mediated immune homeostasis-without adversely affecting global coagulation function. These findings support TPO-RAs as a preferred second-line therapeutic option in this clinical setting.