凝血酶原复合物联合小剂量利妥昔单抗治疗血友病B伴抑制物

Immune tolerance induction in a case of hemophilia B with inhibitor with prothrombin complex concentrate and rituximab

目的探讨血友病B伴抑制物的免疫耐受诱导（ITI）治疗，提高血友病B伴抑制物的诊疗水平。方法应用基于APTT标准曲线的一期法测定重型血友病B患者凝血因子Ⅸ（FⅨ）活性，应用Bethesda法进行FIX抑制物定量测定；利用凝血酶原复合物（PCC）进行ITI并联合利妥昔单抗清除患者抑制物。结果患儿既往PCC暴露日为20d，抑制物滴度峰值为56BU／ml。在2015年11月患儿抑制物滴度降至10．4BU／ml时开始ITI治疗，单用PCC一段时间无效，给予PCC联合利妥昔单抗治疗，17个月后成功清除患者体内FIX抑制物，未发生过敏反应及。肾病综合征等并发症。ITI过程中患者年化出血率有所改善。结论该患者是国内首例报道的采用ITI联合利妥昔单抗成功治疗血友病B伴抑制物的病例。PCC联合利妥昔单抗ITI治疗是目前有希望清除血友病B抑制物的方法。

Objective To explore the immune tolerance induction （ITI） in a case of severe hemophilia B patient with inhibitor. Methods The F IX ： C was detected using a one-stage method and FIX inhibitor was assayed using Bethesda method. ITI was performed with prothrombin complex concentrates （PCC） in combination with rituximab, Results His past exposure days （ED） with PCC were 20 ED and his peak F IX inhibitor titer was 56 BU/ml. When his FIX inhibitor titer decreased to 10.4 BU/ml in Nov. 2015 and after receiving the informed consent from his parents, ITI was started. PCC with low dose rituximab successfully eradicated the high titer inhibitor within 17 months. There was no anaphylaxis, thrombotic event and infection. Conclusion This is the first case report for successful immune tolerance induction therapy in Chinese hemophilia B patient. ITI using PCC combined with rituximab is an effective choice to induce immune tolerance of hemophilia B with inhibitor.