Treatment of refractory thrombotic thrombocytopenic purpura with N-acetylcysteine: a case report
Treatment of refractory thrombotic thrombocytopenic purpura with N-acetylcysteine: a case report
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DOI：
10.1111/trf.12440
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发表时间：
2014-05-01
期刊：
影响因子：
2.9
通讯作者：
Mims, Martha P.
中科院分区：
文献类型：
--
作者：
Li, Gloria W.;Rambally, Siayareh;Mims, Martha P.
血栓性血小板减少性紫癜（TTP）是一种可导致全身微血管血栓形成的危及生命的疾病。这种疾病是由血小板（PLT）过度粘附到加工酶ADAMTS-13不充分切割的超大（UL）血管性血友病因子（VWF）多聚体引起的。虽然许多病例对血浆置换有反应，但同时使用或不使用皮质类固醇，但10%至20%的难治性疾病患者的治疗是困难的。实验研究表明，N-乙酰半胱氨酸（NAC）抑制PLT结合内皮细胞分泌和锚定的UL VWF多聚体表明，NAC可能是有用的治疗TTP。病例报告：一位44岁女性，以不适、意识模糊、胸腹疼痛及短暂性视力丧失来就诊。实验室检查和外周血涂片检查结果与TTP一致。患者开始接受血浆置换和皮质类固醇治疗，但10天后PLT计数仍低于10.0 × 10（9）/L，并出现发热。开始使用利妥昔单抗，但患者病情恶化，陷入昏迷。开始使用抗生素，但培养物保持无菌。昏迷3天后，临床进一步恶化，开始用NAC治疗。患者在1小时内接受负荷剂量150 mg/kg NAC静脉内（IV）给药。在18小时内，患者突然醒来，并开始与医务人员交流。继续进行血浆置换、皮质类固醇、利妥昔单抗和NAC输注（150 mg/kg IV，每日17小时× 10天），到第17天，PLT计数超过50 × 10（9）/L。患者完全康复，并于第31天出院。结论这是首次完整报道的TTP患者NAC治疗。NAC是一种安全有效的辅助治疗难治性TTP的患者。
Background Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease resulting in systemic microvascular thrombosis. The disease is caused by excessive platelet (PLT) adhesion to ultra-large (UL) von Willebrand factor (VWF) multimers inadequately cleaved by the processing enzyme ADAMTS-13. While many cases respond to plasma exchange performed with or without concurrent corticosteroids, treatment of the 10% to 20% of patients with refractory disease is difficult. Experimental studies demonstrating that N-acetylcysteine (NAC) inhibits PLT binding to endothelial cell-secreted and anchored UL VWF multimers suggest that NAC may be useful in the treatment of TTP. Case Report A 44-year-old woman presented with malaise, confusion, chest and abdominal pain, and transient visual loss. Laboratory results and peripheral blood smear were consistent with TTP. The patient was begun on plasma exchange and corticosteroid treatment, but after 10 days the PLT count was still less than 10.0 x 10(9)/L and she developed a fever. Rituximab was initiated, but the patient's condition worsened and she became comatose. Antibiotics were initiated, but cultures remained sterile. After 3 days of coma and further clinical deterioration, treatment with NAC was begun. The patient received a loading dose of 150 mg/kg NAC intravenously (IV) over 1 hour. Within 18 hours the patient awakened abruptly and began communicating with medical personnel. Plasma exchange, corticosteroids, rituximab, and NAC infusion (150 mg/kg IV over 17 hr daily x 10 days) were continued and by Day 17 the PLT count was more than 50 x 10(9)/L. The patient fully recovered and was discharged on Day 31. Conclusion This is the first complete report of a TTP patient treated with NAC. NAC was a safe and effective supplementary treatment for refractory TTP in this patient.