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; Henk te Velthuis; Anke J. M. Eerenberg-Belmer; Aria P. Yazdanbakhsh; Eddy M. F. H. de Beaumont; León Eijsman; Ad Trouwborst; Erik C. Hack

doi:10.1055/s-0037-1614002

Thrombosis and Haemostasis, Table of Contents

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

¹From Department of Anesthesiology, Amsterdam, The Netherlands

,

Henk te Velthuis

³Department of CLB and Laboratory for Experimental and Clinical Immunology, University of Amsterdam, Academic Medical Centre, Amsterdam, The Netherlands

,

Anke J. M. Eerenberg-Belmer

³Department of CLB and Laboratory for Experimental and Clinical Immunology, University of Amsterdam, Academic Medical Centre, Amsterdam, The Netherlands

,

Aria P. Yazdanbakhsh

²Department of Cardiopulmonary Surgery, Academic Medical Centre, Amsterdam, The Netherlands

,

Eddy M. F. H. de Beaumont

¹From Department of Anesthesiology, Amsterdam, The Netherlands

,

León Eijsman

²Department of Cardiopulmonary Surgery, Academic Medical Centre, Amsterdam, The Netherlands

,

Ad Trouwborst

¹From Department of Anesthesiology, Amsterdam, The Netherlands

,

Erik C. Hack

³Department of CLB and Laboratory for Experimental and Clinical Immunology, University of Amsterdam, Academic Medical Centre, Amsterdam, The Netherlands

› Author Affiliations

Abstract

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

Full Text

References

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