移植相关性血栓性微血管病九例临床分析

Clinical analysis of 9 patients with transplant-related thrombotic microangiopathy

目的分析移植相关性血栓性微血管病(TA-TMA)患者的临床特征、治疗及转归。方法回顾性分析2016年1月至2018年8月郑州大学附属肿瘤医院接受造血干细胞移植(HSCT)后发生TA-TMA的9例患者的临床资料。结果9例TA-TMA患者均接受异基因HSCT,男6例,女3例,中位年龄31(12~38)岁。移植至发生TA-TMA的中位时间为76(24~155)d。TA-TMA诊断时血红蛋白中位数为66(58~77)g/L,血小板中位数为22(4~38)×10^9/L,血清乳酸脱氢酶中位数为655(305~4 238)U/L,血尿素氮中位数为15.9(4.8~26.2)mmol/L,血肌酐中位数为118(24~380)μmol/L,中位外周血破碎红细胞比例为2.6%(1.2%~9%)。9例患者尿潜血结果均为阳性,4例同时合并尿蛋白阳性。3例出现神志精神症状。所有患者抗人球蛋白试验(Coombs试验)均阴性。TA-TMA确诊后的主要治疗为钙调磷酸酶抑制剂减停、糖皮质激素及血浆置换的应用。4例患者治疗有效,5例无效。治疗无效的患者破碎红细胞比例、aGVHD等移植相关并发症较重且发生率较高,而治疗有效的患者相对较轻且发生率较低。治疗无效的患者血清LDH水平均明显高于治疗有效的患者,差异有统计学意义。结论TA-TMA是异基因HSCT后的一种严重并发症,起病隐匿,早期诊断困难且治疗手段有限,病死率较高,疗效与诊断时外周血破碎红细胞比例、血清LDH水平及合并症有关。

Objective To analyze the clinical features, efficacy and outcomes in patients with transplantation associated thrombotic microangiopathy (TA-TMA). Methods The clinical data of 9 patients who developed TA-TMA after allogeneic hematopoietic stem cell transplantation (allo-HSCT) were retrospectively analyzed from January 2011 to August 2018 in Affiliated Tumor Hospital of Zhengzhou University. Results There were 6 male and 3 female patiens with a median age of 31 (12-38) years. The median time from transplantation to TA-TMA was 76 (24-155) days. The baseline blood and biochemical parameters at diagnosis of TA-TMA included median hemoglobin (Hb) 66 (58-77) g/L,platelet (PLT) count 22 (4-38)×10^9/L,serum lactic dehydrogenase (LDH) 655 (305-4 238) U/L,blood urine nitrogen (BUN) level 15.9 (4.8-26.2) mmol/L,blood creatinine (Cr) level 118 (24-380)μmol/L. The proportion of median peripheral blood schistocytes was 2.6%(1.2%-9%). All patients had positive urinary occult blood tests,and urinary protein was seen in 4 patients. Three patients had mental symptoms. Coombs tests were all negative. The main treatments of TA-TMA composed of reduction and withdrawal of calcineurin inhibitor,steroids and plasma exchange. Response was seen in 4 patients. Patients who did not response to the treatment had a higher proportion of schistocytes,more severe acute graft-versus-host disease (aGVHD),more elevated serum LDH and other transplant-related complications. Conclusions TA-TMA after allo-HSCT is a serious complication with high mortality rate. The proportion of schistocytes in peripheral blood, serum LDH level and comorbidities are prognostic factors of clinical outcome.