title: Atypical hemolytic uremic syndrome (aHUS): essential aspects of an accurate diagnosis.
abstract: Atypical hemolytic uremic syndrome (aHUS), a thrombotic microangiopathy (TMA), is a rare, life-threatening, systemic disease. When unrecognized or inappropriately treated, aHUS has a high degree of morbidity and mortality. aHUS results from chronic, uncontrolled activity of the alternative complement pathway, which activates platelets and damages the endothelium. Two-thirds of aHUS cases are associated with an identifiable complement-activating condition. aHUS is clinically very similar to the other major TMAs: Shiga toxin-producing Escherichia coli (STEC)-HUS, thrombotic thrombocytopenic purpura (TTP), and disseminated intravascular coagulation (DIC). The signs and symptoms of all the TMAs overlap, complicating the differential diagnosis. Clinical identification of a TMA requires documentation of microangiopathic hemolysis accompanied by thrombocytopenia. DIC must be recognized and treated before it is possible to discriminate among the other 3 major TMAs. STEC-HUS can be excluded through testing for Shiga toxin-producing E. coli. aHUS can be distinguished from TTP on the basis of ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) activity, with a severe decrease characteristic of TTP. This test, as both an activity assay and an inhibitor assay, should be ordered before the initiation of plasma therapy in any patient presenting with a TMA. Finally, it is important to recognize that aHUS remains a clinical diagnosis, but in complex scenarios, tissue biopsy may be a useful adjunct in diagnosis.
authors.affiliation: New York Presbyterian Hospital, Weill Cornell Medical College, New York, New York.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Laurence
authors.affiliation: Hannover Medical School (MHH), Hannover, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Haller
authors.affiliation: IRCCS Cà Granda Foundation Maggiore Policlinico Hospital, Milan, Italy.
authors.forename: Pier Mannuccio
authors.initials: PM
authors.lastname: Mannucci
authors.affiliation: The University of Tokyo Graduate School of Medicine, Tokyo, Japan.
authors.forename: Masaomi
authors.initials: M
authors.lastname: Nangaku
authors.affiliation: Complutense University, Madrid, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Praga
authors.affiliation: El Centro de Investigaciones Biológicas and El Centro de Investigación Biomédica en Red de Enfermedades Raras, Madrid, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Rodriguez de Cordoba
mesh_terms: D000071120:ADAMTS13 Protein / Q000378:metabolism; D000465:Algorithms; D065766:Atypical Hemolytic Uremic Syndrome / Q000097:blood / Q000175:diagnosis* / Q000209:etiology; D003167:Complement Activation; D003165:Complement System Proteins / Q000235:genetics / Q000276:immunology; D003404:Creatinine / Q000097:blood; D003937:Diagnosis, Differential; D004789:Enzyme Activation; D006801:Humans; D010976:Platelet Count; D011697:Purpura, Thrombotic Thrombocytopenic / Q000175:diagnosis; D057049:Thrombotic Microangiopathies / Q000175:diagnosis
chemical_list: D003165:Complement System Proteins; D003404:Creatinine; D000071120:ADAMTS13 Protein