Krishnappa Vinod, Gupta Mohit, Shah Haikoo, Das Abhijit, Tanphaichitr Natthavat, Novak Robert, Raina Rupesh
Department of Internal Medicine and Nephrology, Cleveland Clinic Akron General, 1 Akron General Ave, Akron, OH, 44307, USA.
Department of Nephrology, Weill Cornell Medicine/New York Presbyterian, New York, USA.
BMC Nephrol. 2018 Jan 12;19(1):9. doi: 10.1186/s12882-018-0812-x.
Thrombotic microangiopathy (TMA) secondary to gemcitabine therapy (GiTMA) is a very rare pathology that carries a poor prognosis, with nearly half of the cases progressing to end stage renal disease. GiTMA is most commonly associated with adenocarcinomas, most notably pancreatic cancers. The mainstay of management is withdrawal of the offending drug and supportive care. Plasmapheresis has a limited role and hemodialysis may help in the management of fluid overload secondary to renal failure. Furthermore, a C5 inhibitor, eculizumab, has been successfully used in the treatment of GiTMA.
A 64-year-old Caucasian female with history of pancreatic adenocarcinoma on gemcitabine chemotherapy presented with signs and symptoms of fluid overload and was found to have abnormal kidney function. Her BP was 195/110 mmHg, serum creatinine 4.48 mg/dl, hemoglobin 8.2 g/dl, platelets 53 × 10/cmm, lactate dehydrogenase 540 IU/L, and was found to have schistocytes on blood film. A diagnosis of TMA secondary to gemcitabine therapy was suspected. Hemodialysis for volume overload and daily plasmapheresis were initiated. After six days of plasmapheresis, renal function did not improve. Further work up revealed ADAMTS 13 activity >15%, low C3, and stool culture and Shiga-toxin PCR were negative. Renal biopsy was consistent with TMA. Gemcitabine was discontinued, but renal function failed to improve and eculizumab therapy was considered due to suspicion of aHUS. Serum creatinine >2.26 mg/dl and a platelet count of >/= 30 × 10/L is highly suggestive of aHUS, while TTP is more likely when creatinine is <2.26 mg/dl and platelet count of <30 × 10/L. She received intravenous eculizumab for eight months, which resulted in significant improvement of renal function. Other markers of hemolysis, namely LDH and bilirubin, also rapidly improved following eculizumab therapy. Plasmapheresis and hemodialysis were discontinued after two and eight weeks of initiation respectively.
Chemotherapy induced TMA is very rare and requires a high index of clinical suspicion for timely diagnosis. Discontinuation of the offending drug and supportive care is the main stay of treatment; however, eculizumab has been shown to be beneficial in GiTMA. Further research is required to validate this approach.
吉西他滨治疗继发的血栓性微血管病（GiTMA）是一种非常罕见的病理情况，预后较差，近一半病例会进展至终末期肾病。GiTMA最常与腺癌相关，最显著的是胰腺癌。治疗的主要方法是停用致病药物并给予支持治疗。血浆置换的作用有限，血液透析可能有助于处理肾衰竭继发的液体过载。此外，一种C5抑制剂依库珠单抗已成功用于治疗GiTMA。
一名64岁的白种女性，有胰腺腺癌病史，正在接受吉西他滨化疗，出现了液体过载的症状和体征，且发现肾功能异常。她的血压为195/110 mmHg，血清肌酐4.48 mg/dl，血红蛋白8.2 g/dl，血小板53×10/cmm，乳酸脱氢酶540 IU/L，血涂片检查发现破碎红细胞。怀疑诊断为吉西他滨治疗继发的血栓性微血管病。开始进行血液透析以处理容量过载，并每天进行血浆置换。血浆置换6天后，肾功能未改善。进一步检查发现ADAMTS 13活性>15%，C3降低，粪便培养和志贺毒素PCR均为阴性。肾活检结果符合血栓性微血管病。停用了吉西他滨，但肾功能仍未改善，由于怀疑非典型溶血尿毒症综合征（aHUS），考虑使用依库珠单抗治疗。血清肌酐>2.26 mg/dl且血小板计数≥30×10/L高度提示aHUS，而当肌酐<2.26 mg/dl且血小板计数<30×10/L时更可能是血栓性血小板减少性紫癜（TTP）。她接受了静脉注射依库珠单抗治疗8个月，肾功能得到显著改善。依库珠单抗治疗后，其他溶血指标，即乳酸脱氢酶和胆红素也迅速改善。分别在开始治疗2周和8周后停止了血浆置换和血液透析。
化疗诱导的血栓性微血管病非常罕见，需要高度的临床怀疑指数以实现及时诊断。停用致病药物并给予支持治疗是主要的治疗方法；然而，依库珠单抗已被证明对GiTMA有益。需要进一步研究来验证这种方法。
