Assistant Professor Penn State Health Milton S. Hershey Medical Center, United States
Introduction: Thrombotic microangiopathies (TMA) cause damage to the microvasculature and are broken down into several forms including thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS), and atypical HUS. HUS is commonly caused by Shiga toxin or Shiga like toxin in children. Atypical HUS (aHUS) problematically can be triggered by one of many things including infections, medications, pregnancy, cancer or autoimmune disorders. Here we present a patient with APL who developed atypical HUS related to a recent COVID infection.
Description: A 43 yo man with APL in remission on methotrexate and 6MP, HTN, and DM presented with nausea, vomiting, diarrhea, sore throat and cough. Notably had COVID about 2 weeks prior. He had a Cr 4, new anemia and thrombocytopenia. As renal function worsened, transfer was requested due to concern for MAHA and TMA. Peripheral smear showed schistocytes. Complement and fibrinogen levels were normal, platelets 20, haptoglobin < 10, LDH 1504, and DAT negative. Ultimately had four sessions of plasmapheresis and was started on high dose steroids. He was diagnosed with aHUS as ADAMTS13 was normal. Despite multiple sessions of plasmapheresis, he did not improve and was started on eculizumab with steroid taper. Due to concern that his APL could be contributing, he had a bone marrow biopsy which was negative. He was later discharged on dialysis and scheduled eculizumab infusions.
Discussion: Atypical HUS has in a few cases been attributed to COVID and scenarios have included relapse of aHUS due to COVID and possible direct relationship to new aHUS diagnosis. Our patient developed issues about 2 weeks from the initial infection. COVID 19 activates the complement pathway via the spike surface protein. These patients often have elevated C5b-9 levels which have been correlated to the severity of the illness. His complement levels were normal, not in keeping with the observed trend. His course was also complicated by the fact that he had APL in remission which can be another trigger of aHUS. Ultimately aHUS must be always kept on the differential when renal dysfunction, anemia, and thrombocytopenia are observed in unison. Timing to formal diagnosis is often delayed until ADAMTS13 level is obtained and complement levels are helpful but cannot fully dictate diagnosis.
