A 40 year-old female with no significant past medical history presented with nausea, vomiting, easy bruising, dyspnea on exertion, and presyncope. She had been treated with Levofloxacin for a urinary tract infection one week earlier. Basic lab workup showed hemoglobin of 6.6g/dL, platelets of 56,000, and serum creatinine of 3.69mg/dL. Elevated LDH, indirect bilirubinemia, and a peripheral smear showing (8-10/HPF) schistocytes was consistent with microangiopathic hemolysis. Plasmapheresis was initiated for presumed thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS). ADAMSTS13 activity was normal at >88% with no inhibitor present, raising suspicion for atypical HUS (aHUS). Platelet counts normalized after plasma exchange, and the patient was discharged on oral prednisone. She was re-admitted 9 days later with thrombocytopenia. Plasma exchange was reinitiated and complement factor B, I, and H levels, along with anti-H antibodies were measured. Anti-H titers were found to be elevated. Due to rapid relapse and elevated titers, eculizumab complement blockade was initiated. Platelet counts rebounded after the first infusion, and the patient was committed to a 12-week course of eculizumab.
Atypical HUS (also known as complement-mediated HUS) is a disease entity with unique pathophysiology that often goes unrecognized in patients with the syndrome of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. As suggested by its name, the pathogenesis lies in the dysregulation of the alternative complement pathway. Genetic mutations such as loss-of-function in regulators and gain-of-function in activators alter complement factor function. Dysregulation can also be caused by autoantibodies formed against complement proteins, as in this case. Irrespective of the defect, the end-result is the unregulated assembly of the membrane attack complex (MAC) which damages vascular endothelium (with renal predilection) leading to thrombotic microangiopathy. Common triggers for complement activation include infection, pregnancy, and drugs – Levofloxacin and the urinary tract infection were the presumed triggers in this case. Treatment of aHUS may include complement blockade with eculizumab, a monoclonal antibody to the C5 complement factor found late in the alternative pathway.
Since aHUS has overlapping characteristics with the more common typical HUS and TTP, it is important to have a high level of suspicion in patients presenting with the above-mentioned syndrome without diarrhea and with normal ADAMSTS13 activity. Although all three entities can be treated with plasma exchange initially, the diagnosis of aHUS may require implementation of unique therapeutic strategies such as complement inhibition with eculizumab. Therefore, it is important to recognize the clinical parameters that will lead to prompt diagnosis and initiation of appropriate therapies.
To cite this abstract:Boyechko Y, Lockwood S. Complements to Your Presentation. Abstract published at Hospital Medicine 2015, March 29-April 1, National Harbor, Md. Abstract 462. Journal of Hospital Medicine. 2015; 10 (suppl 2). https://www.shmabstracts.com/abstract/complements-to-your-presentation/. Accessed March 31, 2020.