Case Presentation: A 30 year old woman with history of sickle cell disease presented with complaints of nausea, vomiting and diarrhea for 2-3 days. She was tachycardic and hypotensive on presentation. Pertinent laboratory findings were hemoglobin 9.4 g/dl, platelets 97,000/µL, white count 39,000/µL, glucose 1937 mg/dl, creatinine 2.7 mg/dl and Lipase 567 U/L. Computed tomography (CT) scan of the Abdomen/Pelvis showed acute pancreatitis. Aggressive hydration with IV fluids along with insulin infusion was started. Anemia and thrombocytopenia worsened on day 2 of admission with hemoglobin 5.8 g/dl and platelets 55,000/µL. Lactate dehydrogenase (LDH) was elevated at 553 U/L, haptoglobin was low at <15 mg/dl and peripheral smear revealed 40% schistocytes. Shigella toxin was negative and ADAMTS13 activity was 41%. She required 1 unit of blood transfusion for worsening anemia. On day 3, hyperglycemia had resolved however her mental status progressively worsened which required intubation. Computed tomography (CT) scan of the head showed no acute findings. On day 5, her hemoglobin dropped to 5.0 gm/dl, requiring 2 units of blood transfusion and creatinine was rising to 4.87. The patient was given exchange transfusion and was started on hemodialysis for anuric renal failure. On day 6, a dose of Eculizumab was administered for suspected atypical hemolytic uremic syndrome (aHUS), following which her hemoglobin and creatinine started returning to baseline. Her mental status started improving and she was extubated one week later. Anemia, thrombocytopenia and acute kidney injury (AKI) had completely resolved and she was discharged with close follow up.
Discussion: aHUS or complement-mediated HUS is a rare life-threatening complement-mediated thrombotic microangiopathy which presents as microangiopathic hemolytic anemia, thrombocytopenia, altered mental status and AKI. aHUS is a clinical syndrome which can be triggered by an infectious etiology. It occurs due to gene mutations of complement factors, with a prevalence of one per seven million cases. More than 50% patients are never tested for these mutations because as the tests are expensive and not easily accessible. Eculizumab, a humanized monoclonal antibody to C5, is the only approved medication that shows benefit in severe aHUS with high risk for death or end-stage renal disease (ESRD). In this patient, we hypothesize that acute pancreatitis was the likely trigger. She had remarkable hematological, neurological and renal recovery after one dose of Eculizumab (Figure A).
Conclusions: Since the mortality in aHUS is as high as 25%, physicians should have a high level of suspicion for aHUS. Patients should be tested for complement factor mutations. Treatment with Eculizumab should be started as soon as possible to reduced mortality and progression to ESRD. The current practice is to continue treatment with Eculizumab indefinitely, however emerging case studies have shown that Eculizumab can be successfully discontinued after resolution of precipitant illness.