Use of Eculizumab in the Management of Drug-Induced Thrombotic Microangiopathy: A Case Report

Introduction: The use of complement pathway inhibitor,Eculizumab, for managing drug-induced thrombotic microangiopathy (TMA) is controversial.We describe a patient with cancer who developed TMA and acute kidney injury (AKI) associated with the use of bevacizumab/oxaliplatin.Early identification and use of eculizumab resulted in complete recovery of kidney function. Case Description: 64-year-old female with stage IIb colon cancer on FOLFOX (folinic acid,fluorouracil [5FU],oxaliplatin [Oxa]) & Bevacizumab(Bev) for 6 months,later maintained only on Bev/5FU.2 days after resumption of FOLFOX&Bev infusions,patient was sent to ER by Oncology clinic for reduced urine output, and elevation in serum creatinine (sCr) to 4.96 from 0.65 2 days ago.She was normotensive at presentation, denied diarrhea, reduced fluid intake, NSAIDs or recent IV contrast use.Her hemoglobin was 9.8 (11.3 two days ago) and platelets were 27,000 (90,000 one week ago).Direct and indirect bilirubin were 0.9, AST 97 from 25, LDH 1208 and haptoglobin < 8.Peripheral blood smear revealed 8-10 schistocytes per HPF.Urinalysis revealed hematuria(17 RBCs),proteinuria(>500),glucosuria (50, new).Urine electrolytes were indicative of intrinsic kidney injury.Urine protein/Cr ratio was 2.8g/g and urine microalbumin/Cr ratio was 0.8g/g.ADAMTS-13 levels were normal.The constellation of anemia,thrombocytopenia,elevated LDH,low haptoglobin,schistocytes on peripheral smear and AKI were indicative of microangiopathic hemolytic anemia likely due to Bev/Oxa. Skin biopsy revealed +ve staining for C5b-9 in 8-10 dermal capillaries.Patient was started on Eculizumab 900mg on day 1.There was immediate improvement in hematological markers;however,sCr continued to rise upto 14 over next few days.She underwent a kidney biopsy(10 days after presentation),which revealed severe acute tubular injury with intraluminal material suggestive of hemoglobin casts,diffuse C5b-9 positivity, and focal subacute endothelial injury involving glomeruli with thickening of capillary walls.Patient continued to receive Eculizumab weekly then biweekly with sCr trending down to 1.0 over the course of a month. Discussion: This case highlights the immediate reversal of microangiopathic hemolytic anemia with the use of Eculizumab.Early use of eculizumab likely reduced the severity of kidney injury and aided in the complete recovery of kidney function.