Light at the End of the Tunnel: A Case of Eculizumab in Gemcitabine-Induced Thrombotic Microangiopathy

Introduction: Gemcitabine-induced thrombotic microangiopathy (G-TMA) is a rare life-threatening condition that is underrecognized, underdiagnosed, and underreported. We report a case of a patient with the classic triad of microangiopathic hemolytic anemia, thrombocytopenia, and kidney failure due to G-TMA treated with Eculizumab. Case Description: 50-year-old female with metastatic Mullerian adenocarcinoma on Gemcitabine presented with shortness of breath and leg edema. Vitals included a blood pressure 170/78 mmHg, temperature 37.2°C, respiration 18, and heart rate 96 bpm. Labs were significant for serum creatinine (Scr) 1.9 mg/dL on initial presentation which peaked at 4.3 mg/dL, BUN 53 mg/dL, K 5.9 mmol/L, hemoglobin 7.7 g/dL, platelets 82 K/uL, LDH 514 IU/L, haptoglobin 17 mg/dL, reticulocyte count 4% and urinalysis with small blood and protein 100+. Full paraproteinemia and glomerulonephritis workup was non-revealing, and ADAMTS13 was 89% ruling out thrombotic thrombocytopenic purpura. Although Gemcitabine was discontinued, the acute kidney injury, anemia, and thrombocytopenia continued to worsen. A kidney biopsy confirmed TMA likely due to Gemcitabine therapy which prompted initiation of weekly Eculizumab. She had renal recovery with improved Scr to 2.8mg/dL, hemoglobin to 9.4 g/dL, and platelets to 334 K/uL. Discussion: TMA is classified as primary or secondary. Secondary causes can be due to infection, autoimmune disorder, cancer, or drugs like Gemcitabine. Adverse effects include edema, new onset/exacerbated hypertension, thrombocytopenia, and TMA. The first case of G-TMA was reported in 1994 and its incidence is estimated between 0.02% and 2.2%. It is associated with increased mortality up to 60% and renal injury resulting in end-stage kidney disease. The mechanism is unknown and limited data is available regarding optimal management. Treatment options can include plasma exchange and Eculizumab- a monoclonal anti-C5 antibody that inhibits complement indicated in treating atypical hemolytic uremic syndrome. In our case, she was treated with Eculizumab for G-TMA with partial renal recovery. G-TMA is a challenging diagnosis with unknown recurrence rates and high morbidity-mortality rates in need of therapy guidelines for better outcomes.