What are the underlying pathophysiologic mechanisms of the major TMA syndromes?
• ST-HUS: This is caused by Shiga toxin secreted from strains of Escherichia coli (most common is E. coli O157:H7) or Shigella dysenteriae . Shiga toxin binds to vascular endothelial cells, renal mesangial cells, and renal epithelial cells, leading to cell damage.
• TTP: This is caused by a deficiency in von Willebrand factor–cleaving metalloprotease (A Disintegrin And Metalloproteinase with ThromboSpondin Motifs 13 [ADAMTS13]) that cleaves von Willebrand factor. The deficiency leads to large multimers of von Willebrand factor that increase the risk of platelet thrombi in small vessels.
• aHUS: This is caused by uncontrolled activation of the alternative complement pathway, leading to increased formation of the membrane attack complex injuring normal cells.
