Effect of complement inhibition and heparin coating on artificial surface-induced leukocyte and platelet activation

Ann Thorac Surg. 2004 Mar;77(3):932-41. doi: 10.1016/S0003-4975(03)01519-4.


Background: Exposure of blood to artificial surfaces, as in cardiopulmonary bypass, induces an inflammatory response involving complement, leukocyte and platelet activation. To elucidate the specific role of complement in this process, studies were performed on blood circulated in polyvinyl chloride tubing in the absence and presence of complement inhibitors. Parallel experiments were performed with heparin-coated polyvinyl chloride tubing, which is known to prevent complement and cell activation.

Methods: A novel experimental model was used, based on human whole blood anticoagulated with lepirudin. Complement activation products, myeloperoxidase, lactoferrin, and thrombospondin were quantified in enzyme immunoassays. Leukocyte CD11b expression and leukocyte-platelet conjugates were detected by flow cytometry.

Results: Increased levels of C3 activation products, alternative pathway convertase, and the terminal SC5b-9 complex, combined with unchanged levels of C1rs-C1-inhibitor complexes and marginal changes in C4 activation demonstrated that complement was activated through the alternative pathway. Granulocyte and monocyte CD11b expression and granulocyte-platelet conjugate formation were efficiently attenuated by blocking either factor D, C3, C5, or C5a receptor. In contrast, monocyte-platelet conjugate formation and release of myeloperoxidase, lactoferrin, and thrombospondin were not reduced by complement inhibition. Heparin-coated polyvinyl chloride tubing efficiently reduced all inflammatory markers studied, except for C1rs-C1-inhibitor complexes, which increased, consistent with the enhancing effect of heparin on C1-inhibitor function. This effect did not, however, reduce fluid-phase classic pathway activation induced by heat-aggregated immunoglobulin G.

Conclusions: Leukocyte and platelet activation in response to artificial materials occur by mechanisms that vary in their dependence on complement. Heparin coating precludes both the complement-dependent and complement-independent reactions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • CD11 Antigens / analysis
  • CD11b Antigen / analysis
  • Cardiopulmonary Bypass / adverse effects
  • Cardiopulmonary Bypass / instrumentation*
  • Coated Materials, Biocompatible*
  • Complement Activation*
  • Complement Pathway, Alternative
  • Complement System Proteins / drug effects
  • Flow Cytometry
  • Heparin / pharmacology*
  • Humans
  • Immunoenzyme Techniques
  • In Vitro Techniques
  • Integrin alpha Chains / analysis
  • Lactoferrin / analysis
  • Leukocytes / physiology*
  • Models, Biological
  • Peroxidase / analysis
  • Platelet Activation / drug effects
  • Platelet Activation / physiology*
  • Polyvinyl Chloride*
  • Thrombospondins / analysis


  • CD11 Antigens
  • CD11b Antigen
  • Coated Materials, Biocompatible
  • ITGAD protein, human
  • Integrin alpha Chains
  • Thrombospondins
  • Polyvinyl Chloride
  • Heparin
  • Complement System Proteins
  • Peroxidase
  • Lactoferrin