Sepsis-Induced Thrombotic Microangiopathy (TMA) in Simultaneous Pancreas-Kidney (SPK) Transplantation: Diagnosis and Treatment Dilemmas

Introduction: TMA is an acute life-threatening condition characterized by the formation of microscopic blood clots in capillaries and small arteries, causing microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and organ damage. Case Description: 50-year-old female, with end-stage-renal-disease from diabetes, SPK transplantation in 2018, with baseline creatinine of 1.3mg/dl presented with a week-long history of diarrhea, dysuria, weakness, oliguria, and bilateral flank pain. Found to have acute kidney injury, neutropenia, elevated tacrolimus level (see Table 1). Due to severe neutropenia, mycophenolate was held, and G-CSF initiated. Tacrolimus dose was adjusted for goal level 4 – 6ng/ml. As she was afebrile and initial cultures were negative, patient was monitored off antibiotics. On day four, hemoglobin dropped to 5.8gm/dL with negative hemolytic workup. By day eight, platelet count decreased to 18 x10^3/mcL, with signs of MAHA (see Table 1). Despite daily plasma exchanges and reduced tacrolimus levels, her condition worsened, developing hypotension, and altered mental status. After extensive negative workup, repeat blood cultures revealed ESBL Klebsiella pneumonia bacteremia. She was started on vancomycin and meropenem with clinical improvement. At discharge, creatinine improved to baseline and blood counts and hemolysis stabilized. Discussion: This case highlights the challenge of diagnosing sepsis-induced TMA in the transplant population, with many potential etiologies to consider including Shiga toxin-mediated hemolytic uremic syndrome (ST-HUS), thrombotic thrombocytopenic purpura, complement-mediated TMA (CM-TMA), and drug-induced TMA (DITMA). Antibiotics were vital in her clinical improvement. When managing TMA syndromes in transplant and other immunosuppressed patients, consideration of sepsis in the differential diagnosis is crucial, particularly if standard treatments fail. Table 1. - Admission Day 4 Day 8 Creatinine mg/dl, BUN mg/dl 9.44, 103 6.58, 72 3.25, 46 Tacrolimus level ng/mL 20.1 14.3 9.3 Hgb gm/dL, Platelet x10^3/mcL 8.2, 182 5.8, 92 9, 18 WBC x10^3/mcL, Neutro absolute 10^3/mcL 0.4, 0.3 0.6, 0.4 0.4, 0.1 Reticulocyte, LDH IU/L, Haptoglobin mg/dL, Fibrinogen mg/dLc 1.04%, 130, 169 8.2%, 307, <8 influenza/RSV/COVID/ HIV/Parva B19/ CMV DNA PCR/ stool: O&P/E.coliO:157/salmonella/shigella/ campylobacter/C.diff/Cryptosporidium/Giardia negative HIT antibody/ANA/ Direct Coombs test/ Antiphospholipid antibodies/ ADAMTS13IU/mL negative