Cyclosporine for Thrombotic Thrombocytopenic Purpura
Cyclosporine for Thrombotic Thrombocytopenic Purpura
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环孢素治疗血栓性血小板减少性紫癜
DOI：
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发表时间：
1993
影响因子：
39.2
通讯作者：
B. Heintz
中科院分区：
文献类型：
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作者：
H. Kierdorf;N. Maurin;B. Heintz
致编辑：血栓性血小板减少性紫癜包括血小板减少、微血管致病性溶血性贫血、波动神经体征、发热和肾损害[1]。主要的治疗方式是血浆置换，有时与抗血小板治疗联合使用。脾切除术和免疫抑制治疗在反应较差的情况下被使用[2,3]。我们描述了一位64岁的男性，他的疾病在血浆置换失败后由环孢素控制。入院时，患者神志不清，有不明原因的发热（体温39.1℃），肝脏轻度肿大，血红蛋白浓度97 g/L，血小板计数31000 /mm3，红细胞碎裂（占所有红细胞的25%），蛋白尿和血尿。肌酐（250 mol/L）、尿素（14 mmol/L）、胆红素（69 mol/L）、乳酸脱氢酶（1500 IU/L，正常范围80 ~ 240 IU/L）升高。未检测到自身抗体。库姆斯试验呈阴性；排除弥漫性血管内凝血。诊断为血栓性血小板减少性紫癜，并开始治疗，每隔一天3升血浆交换。另外，给予阿司匹林、双嘧达莫和前列环素。未见稳定缓解，15天后治疗无效。第20天停用常规治疗，给予环孢素300 mg/d。3天内达到治疗水平，8天内完全缓解。环孢素治疗持续3个月，患者自行停药。停用环孢素治疗3个月后，患者复发，特征为血小板减少（40000 /mm3）、贫血（血红蛋白90g /L）、神经系统症状和肌酐水平升高。单独使用环孢素（300 mg/d）治疗，10天内完全缓解。患者在环孢素治疗9个月后临床和血液学完全缓解（图1）。虽然血浆置换术降低了与血栓性血小板减少性紫癜相关的死亡率，但无论是单独使用还是与抗血小板药物联合使用，它都不是普遍有效的[2,3]。由于一些血栓性血小板减少性紫癜患者有细胞毒性抗体，免疫抑制剂如强的松龙、硫唑嘌呤、长春新碱、环磷酰胺和免疫球蛋白已被经验地用于提出的免疫损伤[3-5]。图1所示。在两种常规治疗期间，血小板计数和乳酸脱氢酶（LDH）活性(C.环孢素单独治疗似乎诱导了一名对常规治疗有抵抗力的血栓性血小板减少性紫癜患者的缓解，并且在患者经历随后的复发时也有效。与其他免疫抑制疗法相比，环孢素副作用较少，可能被证明是慢性血栓性血小板减少性紫癜患者的有用替代疗法。
TO THE EDITOR: Thrombotic thrombocytopenic purpura consists of thrombocytopenia, microangiopathic hemolytic anemia, fluctuating neurologic signs, fever, and renal impairment [1]. The primary treatment modality is plasmapheresis, which is sometimes combined with antiplatelet therapy [2]. Splenectomy and immunosuppressive therapy have been used where the response is poor [2, 3]. We describe a 64-year-old man in whom the disease was controlled by cyclosporine after plasmapheresis failed. When admitted, he was in a confused state and had an unexplained fever (temperature, 39.1 C), a slightly enlarged liver, a hemoglobin concentration of 97 g/L, a platelet count of 31 000/mm3, red cell fragmentation (25% of all erythrocytes), proteinuria, and hematuria. Creatinine (250 mol/L), urea (14 mmol/L), bilirubin (69 mol/L), and lactic dehydrogenase (1500 IU/L; normal range, 80 to 240 IU/L) levels were increased. No autoantibodies were detected. Coombs tests were negative; disseminated intravascular coagulation was excluded. Thrombotic thrombocytopenic purpura was diagnosed, and treatment was begun with a 3-liter plasma exchange every second day. In addition, aspirin, dipyridamole, and prostacyclin were administered. No stable remission could be achieved, and after day 15 treatment was ineffective. On day 20, conventional therapy was discontinued and cyclosporine, 300 mg/d, was instituted. Therapeutic blood levels were attained within 3 days, and complete remission occurred within 8 days. Cyclosporine therapy was continued for 3 months and stopped by the patient. Three months after discontinuing cyclosporine treatment, the patient had a relapse that was characterized by thrombocytopenia (40 000/mm3), anemia (hemoglobin, 90 g/L), neurologic symptoms, and an increased creatinine level. Cyclosporine (300 mg/d) was administered as the sole therapy, and complete remission was achieved within 10 days. The patient has been in full clinical and hematologic remission for 9 months on cyclosporine (Figure 1). Although plasmapheresis has reduced the mortality associated with thrombotic thrombocytopenic purpura, it is not universally effective, either alone or in combination with antiplatelet agents [2, 3]. Because some patients with thrombotic thrombocytopenic purpura have cytotoxic antibodies, immunosuppressive agents such as prednisolone, azathioprine, vincristine, cyclophosphamide, and immunoglobulins have been used empirically for the proposed immunologic damage [3-5]. Figure 1. Platelet count and lactic dehydrogenase (LDH) activity during both conventional treatment (C. Cyclosporine alone appears to have induced a remission in one patient with thrombotic thrombocytopenic purpura resistant to conventional therapy and was also effective when the patient experienced a subsequent relapse. In contrast to other immunosuppressive therapy, cyclosporine has fewer side effects and may prove to be a useful alternative therapy for patients with chronic thrombotic thrombocytopenic purpura.