Blood Journal
Leading the way in experimental and clinical research in hematology

Complement anaphylatoxin C5a contributes to hemodialysis-associated thrombosis

  1. Ioannis Kourtzelis1,
  2. Maciej M. Markiewski2,
  3. Michael Doumas3,
  4. Stavros Rafail2,
  5. Konstantinos Kambas1,
  6. Ioannis Mitroulis1,
  7. Stelios Panagoutsos4,
  8. Ploumis Passadakis4,
  9. Vasilios Vargemezis4,
  10. Paola Magotti2,
  11. Hongchang Qu2,
  12. Tom Eirik Mollnes5,
  13. Konstantinos Ritis1, and
  14. John D. Lambris2,*
  1. 1 First Department of Internal Medicine Medical School, Democritus University of Thrace, Alexandroupolis, Greece;
  2. 2 Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA, United States;
  3. 3 Second Propedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece;
  4. 4 Department of Nephrology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece;
  5. 5 Institute of Immunology, University of Oslo and Rikshospitalet University Hospital, Oslo, Norway
  1. * Corresponding author; email: lambris{at}


Thrombosis is a common complication of end-stage renal disease (ESRD), 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. Since 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 ESRD patients. Furthermore, we found that complement contributed to the induction of granulocyte colony stimulating factor (G-CSF), 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 G-CSF 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.

  • Submitted January 13, 2010.
  • Accepted April 14, 2010.