Blood Rev. 2017 Jul;31(4):213-223. doi: 10.1016/j.blre.2017.02.003. Epub 2017 Feb 6.


The complement system is an essential part of the innate immune system that requires careful regulation to ensure responses are appropriately directed against harmful pathogens, while preventing collateral damage to normal host cells and tissues. While deficiency in some components of the complement pathway is associated with increased susceptibility to certain infections, it has also become clear that inappropriate activation of complement is an important contributor to human disease. A number of hematologic disorders are driven by complement, and these disorders may be termed "complementopathies". This includes paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), cold agglutinin disease (CAD) and other related disorders, which will be the focus of this review. A better understanding of the central role of the complement system in the pathophysiology of these disorders may allow for application of therapies directed at blocking the complement cascade.

Keywords: Alternative pathway of complement; Atypical hemolytic uremic syndrome; Cold agglutinin disease; Complementopathy; HELLP syndrome; Paroxysmal nocturnal hemoglobinuria.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptive Immunity
  • Anemia, Hemolytic, Autoimmune / immunology*
  • Anemia, Hemolytic, Autoimmune / pathology
  • Anemia, Hemolytic, Autoimmune / therapy
  • Animals
  • Atypical Hemolytic Uremic Syndrome / immunology*
  • Atypical Hemolytic Uremic Syndrome / pathology
  • Atypical Hemolytic Uremic Syndrome / therapy
  • Complement Activation*
  • Complement System Proteins / immunology*
  • Female
  • HELLP Syndrome / immunology*
  • HELLP Syndrome / pathology
  • HELLP Syndrome / therapy
  • Hemoglobinuria, Paroxysmal / immunology*
  • Hemoglobinuria, Paroxysmal / pathology
  • Hemoglobinuria, Paroxysmal / therapy
  • Humans
  • Immunity, Innate
  • Pregnancy


  • Complement System Proteins