How I treat: the clinical differentiation and initial treatment of adult patients with atypical hemolytic uremic syndrome

Abstract

Published data demonstrating the efficacy of complement inhibition therapy in patients with atypical hemolytic uremic syndrome (aHUS) are remarkable in contrast to the historically poor long-term prognosis for aHUS patients treated with plasma-based therapy. Although both aHUS and acquired thrombotic thrombocytopenic purpura (TTP) remain clinical diagnoses, an increased understanding of both conditions has improved our ability to differentiate aHUS from acquired TTP. These same data have also demonstrated the importance of a more rapid identification and diagnosis of aHUS as the recovery of end-organ injury present appears to be related to the time to initiate therapy with eculizumab. The diagnosis of acquired TTP can be confirmed by the finding of severely deficient ADAMTS13 activity (<10%) with evidence of an ADAMTS13 antibody inhibitor whereas merely deficient ADAMTS13 activity in the absence of an ADAMTS13 autoantibody is more consistent with congenital TTP. In the absence of an objective diagnostic test, clinicians must rely collectively on platelet count, serum creatinine, and ADAMTS13 activity in the context of the response to plasma exchange therapy to identify patients whose diagnosis is most consistent with aHUS, and thus be more likely to benefit from therapy with eculizumab.