A Mechanistic Approach to the Diagnosis and Management of Atypical Hemolytic Uremic Syndrome

Until recently, atypical hemolytic uremic syndrome (aHUS), conventionally defined in the pediatric literature as a syndrome of the triad of renal failure, microangiopathic hemolytic anemia, and thrombocytopenia without a prodrome of hemorrhagic diarrhea, has received little attention in adult practice because the patients are commonly given the diagnosis of thrombotic thrombocytopenic purpura (TTP) or TTP/HUS and treated as TTP with plasma exchange, augmented in refractory cases with rituximab and sometimes even splenectomy. Molecular studies have shown that the regulation of the alternative complement pathway is defective in many patients with conventionally defined aHUS. With this new knowledge and the findings of ADAMTS13 autoinhibitors or mutations in TTP, it is time to redefine aHUS as a disorder with propensity to the development of thrombotic microangiopathy due to defective regulation of the alternative complement pathway and TTP as a disorder with propensity to arteriolar and capillary thrombosis due to ADAMTS13 deficiency. This new definition provides a clear distinction of aHUS from TTP, encompasses patients without all 3 components of the triad, and provides the rationale for management with anticomplement therapy.