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Specific complement inhibition with heparin-coated extracorporeal circuits
H te Velthuis1, P G Jansen, C E Hack
1Centre for Cardiopulmonary Surgery Amsterdam, The Netherlands.
Insights
Heparin-coated circuits reduce complement activation during heart surgery, specifically the alternative and terminal pathways. This suggests C3b/c is a better marker than C3a for assessing complement activation.
Area of Science:
- Cardiovascular Surgery
- Biomedical Engineering
- Immunology
Background:
- Heparin-coated circuits are known to reduce complement activation in cardiac surgery.
- Limited in vivo data exists on their impact on alternative and classic complement pathways.
Purpose of the Study:
- To compare complement activation in patients undergoing coronary artery bypass grafting using heparin-coated versus uncoated extracorporeal circuits.
- To assess alternative, classic, and terminal complement pathway activation in vivo.
Main Methods:
- Prospective, randomized study of 20 patients undergoing coronary artery bypass grafting.
- Comparison of heparin-coated (Duraflo II) circuits with uncoated circuits.
- Measurement of complement activation products: iC3, C4b/c, soluble C5b-9, C3a, and C3b/c.
Main Results:
- Heparin-coated circuits significantly reduced C3b/c and soluble C5b-9 concentrations post-cardiopulmonary bypass.
- No significant reduction was observed in iC3, C4b/c, or C3a concentrations.
- Reductions were sustained after protamine sulfate administration.
Conclusions:
- Heparin-coated circuits effectively reduce alternative complement pathway activation at the C3 convertase level.
- This leads to downstream reduction in terminal complement pathway activation.
- C3b/c is a more sensitive marker than C3a for assessing complement activation during cardiac operations.
Background:
Although it is well established that heparin-coated extracorporeal circuits reduce complement activation during cardiac operations, little in vivo information is available on the reduction in alternative and classic pathway activation.
Methods:
In a prospective, randomized study involving patients undergoing coronary artery bypass grafting with standard full heparinization, we compared heparin-coated circuits (Duraflo II) (10 patients) with uncoated circuits (10 patients) and assessed the extent of initiation of complement activation by detecting iC3 (C3b-like C3) concentrations, classic pathway activation by C4b/c (C4b, iC4b, C4c) concentrations, terminal pathway activation by soluble C5b-9 concentrations, and C3 activation by C3a (C3a desArg) and C3b/c (C3b, iC3b, C3c) concentrations.
Results:
Heparin-coated extracorporeal circuits significantly reduced circulating complement activation product C3b/c and soluble C5b-9 concentrations at the end of cardiopulmonary bypass and after protamine sulfate administration compared with the uncoated circuits, but not iC3, C4b/c, or C3a concentrations.
Conclusions:
Heparin-coated extracorporeal circuits reduce complement activation through the alternative complement pathway, probably at the C3 convertase level, and, consequently, the terminal pathway. C3b/c seems to be a more sensitive marker than C3a to assess complement activation during cardiac operations.