Department of Medicine, Section of Hematology Oncology, Baylor College of Medicine, Houston, Texas; The Hematology Service, Ben Taub General Hospital, Houston, Texas.
Transfusion. 2014 May;54(5):1221-4. doi: 10.1111/trf.12440. Epub 2013 Oct 9.
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.
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 × 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 × 10 days) were continued and by Day 17 the PLT count was more than 50 × 10(9) /L. The patient fully recovered and was discharged on Day 31.
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.
血栓性血小板减少性紫癜（TTP）是一种危及生命的疾病，会导致全身微血管血栓形成。该病是由于超大（UL）型 von Willebrand 因子（VWF）多聚体的过度血小板（PLT）黏附，而这种多聚体不能被加工酶 ADAMTS-13 充分剪切。虽然许多病例对血浆置换治疗有反应，无论是否同时使用皮质类固醇，但对 10%至 20%的难治性疾病患者的治疗都很困难。实验研究表明，N-乙酰半胱氨酸（NAC）可抑制 PLT 与内皮细胞分泌和锚定的 UL VWF 多聚体的结合，提示 NAC 可能对 TTP 的治疗有用。
一名 44 岁女性出现不适、意识模糊、胸痛和腹痛，以及短暂性视力丧失。实验室结果和外周血涂片与 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，且出现发热。开始使用利妥昔单抗，但患者病情恶化并陷入昏迷。开始使用抗生素，但培养结果仍为无菌。昏迷 3 天后，病情进一步恶化，开始使用 NAC 治疗。患者接受了 150mg/kg 的 NAC 负荷剂量静脉输注（IV），持续 1 小时。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（150mg/kg IV 持续 17 小时，每天一次×10 天），第 17 天 PLT 计数超过 50×10^9/L。患者完全康复，第 31 天出院。
这是首例用 NAC 治疗 TTP 患者的完整报告。在该患者中，NAC 是难治性 TTP 的一种安全有效的辅助治疗方法。
