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Thromb Haemost 2000; 84(02): 237-243
DOI: 10.1055/s-0037-1614002
Review Article
Schattauer GmbH

Heparin-protamine Complexes and C-reactive Protein Induce Activation of the Classical Complement Pathway: Studies in Patients Undergoing Cardiac Surgery and In Vitro

Peter Bruins
1   From Department of Anesthesiology, Amsterdam, The Netherlands
,
Henk te Velthuis
3   Department of CLB and Laboratory for Experimental and Clinical Immunology, University of Amsterdam, Academic Medical Centre, Amsterdam, The Netherlands
,
Anke J. M. Eerenberg-Belmer
3   Department of CLB and Laboratory for Experimental and Clinical Immunology, University of Amsterdam, Academic Medical Centre, Amsterdam, The Netherlands
,
Aria P. Yazdanbakhsh
2   Department of Cardiopulmonary Surgery, Academic Medical Centre, Amsterdam, The Netherlands
,
Eddy M. F. H. de Beaumont
1   From Department of Anesthesiology, Amsterdam, The Netherlands
,
León Eijsman
2   Department of Cardiopulmonary Surgery, Academic Medical Centre, Amsterdam, The Netherlands
,
Ad Trouwborst
1   From Department of Anesthesiology, Amsterdam, The Netherlands
,
Erik C. Hack
3   Department of CLB and Laboratory for Experimental and Clinical Immunology, University of Amsterdam, Academic Medical Centre, Amsterdam, The Netherlands
› InstitutsangabenThe authors thank Mrs. W. M. Morriën-Salomons and Mr. Gerard van Mierlo for their excellent assistance with the assays.
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Publikationsverlauf

Received 24. Januar 2000

Accepted after revision 22. März 2000

Publikationsdatum:
14. Dezember 2017 (online)

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Summary

The administration of protamine to patients undergoing cardiopulmonary bypass (CPB) to neutralize heparin and to reduce the risk of bleeding, induces activation of the classical complement pathway mainly by heparin-protamine complexes. We investigated whether C-reactive protein (CRP) contributes to protamine-induced complement activation.

In 24 patients during myocardial revascularization, we measured complement, CRP, and complement-CRP complexes, reflecting CRPmediated complement activation in vivo. We also incubated plasma from healthy volunteers and patients with heparin and protamine in vitro to study CRP-mediated complement activation. During CPB, CRP levels remained unchanged while C3 activation products increased. C4 activation occurred after protamine administration. CRP-complement complexes increased at the end of CPB and upon protamine administration. Incubation of plasma with heparin and protamine in vitro generated complement-CRP complexes, which was blocked by phosphorylcholine and stimulated by exogenous CRP. C4d-CRP complex formation after protamine administration correlated clinically with the incidence of postoperative arrhythmia.

Protamine administration during cardiac surgery induces complement activation which in part is CRP-dependent, and correlates with postoperative arrhythmia.

Keywords

C-reactive protein - heparin - protamine - complement - extracorporeal circulation
 

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