Thrombotic Thrombocytopenic Purpura, Atypical Hemolytic Uremic Syndrome, and Spectrum of Thrombotic Microangiopathy

Abstract

Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) are thrombotic microangiopathies (TMAs) which are characterized by microangiopathic hemolytic anemia (MAHA) and thrombocytopenia and show significant overlap in clinical presentation but are distinct in their underlying pathology. TTP is caused by an inherited or acquired deficiency in a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13). ADAMTS13 cleaves von Willebrand factor (VWF) when released from endothelial cells, thus preventing the accumulation of prothrombotic ultra-large VWF (ULFWF) multimers. By difference, hemolytic uremic syndrome (HUS) is caused by infections with Shiga toxin (Stx)-producing Escherichia coli (E. coli; STEC HUS). And in the atypical form of HUS (aHUS), the endothelial injury is caused by complement dysregulation due to genetic (gain-or loss-of-function mutations) or autoimmune (inhibiting autoantibodies) causes. Recently, transient complement dysregulation has also been recognized in the absence of mutations and autoantibodies but rather as a consequence of infections, autoimmune diseases, drugs, mechanical endothelial injury, etc., thus defining a spectrum of secondary TMAs. The advent of high precision medications which allow for the safe and efficient treatment of aHUS and TTP has fundamentally changed patient outcomes and quality of life.