Complement anaphylatoxin C5a contributes to hemodialysis-associated thrombosis

Blood. 2010 Jul 29;116(4):631-9. doi: 10.1182/blood-2010-01-264051. Epub 2010 Apr 27.


Thrombosis is a common complication of end-stage renal disease, particularly in patients on hemodialysis. Although substantial progress has been made in preventing thrombotic complications in various other groups of patients, the mechanisms of thrombosis during hemodialysis require clarification. In this report, we demonstrate that complement activation triggered by hemodialysis biomaterials, and the subsequent generation of the complement anaphylatoxin C5a, results in the expression of functionally active tissue factor (TF) in peripheral blood neutrophils. Because TF is a key initiator of coagulation in vivo, we postulate that the recurring complement activation that occurs during long-term hemodialysis contributes to thrombosis in dialyzed end-stage renal disease patients. Furthermore, we found that complement contributed to the induction of granulocyte colony-stimulating factor, which has been implicated in the pathogenesis of thrombosis in patients treated with the recombinant form of this molecule. Importantly, the inhibition of complement activation attenuated the TF expression and granulocyte colony-stimulating factor induction in blood passing through a hemodialysis circuit, suggesting that the complement system could become a new therapeutic target for preventing thrombosis in patients with chronic renal failure who are maintained on hemodialysis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Anaphylatoxins / pharmacology
  • Anaphylatoxins / physiology
  • Blood Coagulation / drug effects
  • Cells, Cultured
  • Complement Activation / drug effects
  • Complement C5a / metabolism
  • Complement C5a / pharmacology
  • Complement C5a / physiology*
  • Female
  • Granulocyte Colony-Stimulating Factor / metabolism
  • Humans
  • Kidney Failure, Chronic / blood
  • Kidney Failure, Chronic / complications
  • Kidney Failure, Chronic / metabolism
  • Kidney Failure, Chronic / therapy
  • Leukocytes / drug effects
  • Leukocytes / metabolism
  • Leukocytes / pathology
  • Male
  • Middle Aged
  • Receptor, Anaphylatoxin C5a / metabolism
  • Renal Dialysis / adverse effects*
  • Thromboplastin / metabolism
  • Thrombosis / etiology*
  • Time Factors


  • Anaphylatoxins
  • Receptor, Anaphylatoxin C5a
  • Granulocyte Colony-Stimulating Factor
  • Complement C5a
  • Thromboplastin