Atypical hemolytic uremic syndrome: Review of clinical presentation, diagnosis and management

Abstract

Thrombotic microangiopathies (TMA) are a class of disorders characterized by microangiopathic hemolytic anemia, non-immune thrombocytopenia, and organ dysfunction. One type of TMA is atypical hemolytic uremic syndrome (aHUS) a disorder caused by hyper-activation of the alternative complement pathway due to over activation of C3 convertases and loss of complement regulatory mechanisms. The pathophysiological mechanism of aHUS involves increased continuous spontaneous hydrolysis of C3 to C3b which leads to tissue deposition of C3b, the membrane attack complex formation and subsequent tissue injury. The underlying susceptibility factors to aHUS include acquired autoantibodies or germline mutations in complement proteins or their regulators. Currently there are no clear diagnostic criteria for aHUS. Diagnosis involves ruling out other causes of TMA and incorporating complement serologic and genetic data. TPE has been used to treat aHUS; however, clinical improvement in these patents is far less than in patients with thrombotic thrombocytopenic purpura. Furthermore, there is a higher rate of progression to end stage renal disease with almost half of patients progressing despite TPE. For those, another option for treatment is eculizumab, a monoclonal antibody that blocks complement C5. Eculizumab has proven effective in aHUS and dramatically changed the prognosis of this syndrome. In this review the clinical presentation, diagnosis and management of aHUS are highlighted with three clinical cases.

Keywords: Atypical hemolytic uremic syndrome; Complement; Eculizumab; Terminal complement inhibitor; Thrombotic microangiopathy.