Case Presentation: A 41-year old-woman with history of Hashimoto’s thyroiditis was transferred from referring hospital (OSH) for persistent thrombocytopenia. Patient was well until one month prior to presentation, when she presented for right upper quadrant (RUQ) pain. The patient was diagnosed with gallstone cholecystitis and underwent laparoscopic cholecystectomy. At the time of her surgery, she was found to be anemic to hemoglobin of 7 g/dL with a MCV of 63fL, and thrombocytopenic with platelet count of 108,000 per μL. She tolerated the cholecystectomy without complications and was discharged home. One week later, she re-presented to OSH with fever, severe abdominal pain and altered mental status. She was found to have leukocytosis of 20,000 per μL and severely thrombocytopenic with platelet of 10,000 per μL. Fibrinogen was 177 mg/dL and haptoglobin was 54 mg/dL. Patient was admitted and started on cefepime, vancomycin and metronidazole. Her hospital course was complicated by acute kidney injury with creatinine of 1.8mg/dL (baseline 0.9mg/dL), ongoing anemia requiring multiple blood transfusions and persistent fever despite antibiotics. Kidney biopsy was performed which demonstrated diffuse and global thrombotic microangiopathy. To evaluate for primary hematologic disorder, bone marrow biopsy was obtained and did not show any increase in CD34+ blasts, monoclonal B- or T-cell populations.Patient had a PLASMIC score of 6, indicating high risk for having thrombocytopenic thrombotic purpura (TTP). Patient was started on plasmapheresis and ADAMTS13 level was obtained. ADAMTS13 level was 47 (reference range >70), which was higher than expected with TTP. Patient continued to be thrombocytopenic despite three plasma exchanges. In discussion with the nephrology and transfusion medicine teams, it was decided that patient’s presentation is more consistent with atypical hemolytic-uremic syndrome (aHUS). Therefore, plasma exchange was discontinued, and the patient was started on eculizumab. Upon starting eculizumab, the patient’s renal function improved. Her thrombocytopenia improved with platelet of 56,000 per μL.
Discussion: aHUS is a rare disorder caused by genetic or acquired defect in regulation of complement activation on host cells. . Differentiating aHUS from other thrombotic microangiopathies such as TTP on presentation can be challenging given the lack of a clear differentiating test. More importantly, early diagnosis and treatment can prevent chronic renal failure. Complement activation and dysregulation is central to the pathogenesis of aHUS but having normal complement levels do not rule it out, like in our patient. This case demonstrated that the combination of clinical and laboratory data, activity of ADAMTS13, and lack of response to plasma exchange allows for differentiation between aHUS and TTP.
Conclusions: aHUS is a rare condition characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia and renal impairment. Although primarily affects children, few cases have been reported in adults. Prompt diagnosis of aHUS is essential since delayed treatment can cause terminal chronic renal failure necessitating dialysis. Differentiating aHUS from TTP can be challenging but clinicians should use clinical history, laboratory data and response to plasma exchange to diagnose aHUS.