Update in the diagnosis of complement-mediated thrombotic microangiopathy/atypical hemolytic uremic syndrome

Abstract

Complement-mediated thrombotic microangiopathy (C-TMA), also referred to as atypical hemolytic uremic syndrome (aHUS), is a rare but severe cause of microangiopathic hemolysis and organ injury. Despite advances in understanding its pathophysiology and new nomenclature distinguishing C-TMA (aHUS) from other TMAs, diagnosis remains difficult because there is no single definitive diagnostic test. This update focuses on emerging data for functional complement assays (eg, modified Ham assay and human microvascular endothelial cell (HMEC-1) C5b-9 deposition assays) as adjunctive tests that may directly demonstrate complement hyperactivity in suspected C-TMA. A systematic diagnostic algorithm incorporating rapid exclusion of thrombotic thrombocytopenic purpura and Shiga toxin-producing Escherichia coli-HUS, careful evaluation of secondary causes, and integration of genetic and functional testing may improve diagnostic accuracy and guide the prompt use of targeted complement inhibitors.