Xenotransplantation Research Center, Seoul, Korea.
Institute of Endemic Diseases, Seoul, Korea.
Xenotransplantation. 2018 Sep;25(5):e12404. doi: 10.1111/xen.12404. Epub 2018 May 18.
Tacrolimus-associated thrombotic microangiopathy (TA-TMA) is a rare complication. TA-TMA is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and organ damage due to thrombus. We report asymptomatic TA-TMA diagnosed by laboratory tests in pig-to-rhesus corneal xenotransplantation. Corneal transplantation had been conducted from a wild-type SNU miniature pig to a rhesus macaque. The veterinary records were retrospectively reviewed in this case. The immunosuppressive regimen consisted of rituximab, basiliximab, and IVIg as inductive therapies, and steroids with tacrolimus (0.1 mg/kg/day) as maintenance therapies. Although there were no clinical symptoms, increased levels of lactate dehydrogenase, total bilirubin, blood urea nitrogen, and creatinine and decreased levels of hemoglobin and platelet were observed in laboratory tests on Day (D) 61. Systemic TA-TMA was tentatively diagnosed. Tacrolimus was discontinued starting on D71. Dalteparin, clopidogrel bisulfate (D77-D99), and IVIg (D72) were administered as a conservative treatment. Abnormal laboratory results were reversed on D99. When low-dose tacrolimus (0.07 mg/kg/day) was re-administered on D131 to prevent rejection of the graft, TMA was detected again by laboratory tests on D161, confirming the initial diagnosis. Discontinuation of tacrolimus on D162 and re-administration of Dalteparin (D161-D196) corrected the laboratory values on D161. This report shows that in pig-to-rhesus corneal xenotransplantation, clinically asymptomatic TMA can be induced by tacrolimus, and the discontinuation of tacrolimus and administration of anticoagulant seems sufficient to correct the laboratory TMA.
他克莫司相关性血栓性微血管病（TA-TMA）是一种罕见的并发症。TA-TMA 的特征是微血管性溶血性贫血、血小板减少症和血栓导致的器官损伤。我们报告了一例在猪-恒河猴角膜异种移植中通过实验室检查诊断为无症状 TA-TMA 的病例。角膜移植是从野生型 SNU 小型猪到恒河猴进行的。本病例回顾性审查了兽医记录。免疫抑制方案包括利妥昔单抗、巴利昔单抗和 IVIg 作为诱导治疗，以及类固醇联合他克莫司（0.1mg/kg/天）作为维持治疗。尽管没有临床症状，但在第 61 天的实验室检查中观察到乳酸脱氢酶、总胆红素、血尿素氮和肌酐水平升高，血红蛋白和血小板水平降低。疑似诊断为系统性 TA-TMA。从第 71 天开始停用他克莫司。给予达肝素钠、硫酸双氯芬酸（D77-D99）和 IVIg（D72）作为保守治疗。第 99 天实验室结果恢复正常。当第 131 天重新给予低剂量他克莫司（0.07mg/kg/天）以预防移植物排斥时，第 161 天实验室检查再次发现 TMA，证实了最初的诊断。第 162 天停用他克莫司，第 161-196 天再次给予达肝素钠纠正了第 161 天的实验室值。本报告表明，在猪-恒河猴角膜异种移植中，他克莫司可引起临床无症状性 TMA，停用他克莫司和给予抗凝剂似乎足以纠正实验室 TMA。
