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Xenotransplantation. 2018 Sep;25(5):e12404. doi: 10.1111/xen.12404. Epub 2018 May 18.

Tacrolimus-induced asymptomatic thrombotic microangiopathy diagnosed by laboratory tests in pig-to-rhesus corneal xenotransplantation: A case report.

Kim JM1,2,3,4, Kim J5,6,7, Choi SH5,6, Shin JS1,2,3,4,8, Min BH1,3,8, Jeong WY1, Lee GE1, Kim MS1, Kwon S1, Kim MK1,5,6, Park CG1,2,3,4,8,9.

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Xenotransplantation Research Center, Seoul, Korea.
Institute of Endemic Diseases, Seoul, Korea.
Cancer Research Institute, Seoul, Korea.
Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea.
Laboratory Of Ocular Regenerative Medicine and Immunology, Seoul Artificial Eye Center, Seoul National University Hospital Biomedical Research Institute, Seoul, Korea.
Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Korea.
Department of Ophthalmology, Seoul Paik Hospital, Inje University College of Medicine, Seoul, Korea.
Department of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Korea.
Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea.


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.


calcineurin inhibitor; rhesus macaque; tacrolimus; thrombotic microangiopathy; transplantation

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