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J Thorac Cardiovasc Surg 1995;109:765-771
© 1995 Mosby, Inc.

CARDIOPULMONARY BYPASS, MYOCARDIAL MANAGEMENT, AND SUPPORT TECHNIQUES

Reversal of heparin anticoagulation by recombinant platelet factor 4 and protamine sulfate in baboons during cardiopulmonary bypass

Philadelphia, Pa.

Supported by HL 47186 and 47456 from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda Md.

Address for reprints: L. Henry Edmunds, Jr., MD, Division of Cardiothoracic Surgery, Hospital of the University of Pennsylvania, 3400 Spruce St., Philadelphia, PA 19104.

Abstract

The ability of recombinant platelet factor 4 and protamine to neutralize heparin after cardiopulmonary bypass was compared in anesthestized baboons. Clotting titration curves of heparinized baboon blood demonstrate an anticoagulant effect of protamine that is not seen with recombinant platelet factor 4. Neither drug caused meaningful changes in central pressures or cardiac output within 30 minutes after injection. After 30 minutes of cardiopulmonary bypass, recombinant platelet factor 4 normalized thrombin times and activated partial thromboplastin times within 5 minutes of injection, but protamine did not. Neither drug altered bleeding times. Recombinant platelet factor 4 caused a species-specific leukopenia in baboons and significantly increased activated complement protein 3 (C3a) more than protamine. However, the increase in plasma C3a was small and neither drug caused a significant increase in plasma neutrophil elastase-₁ proteinase inhibitor complex. We conclude that recombinant platelet factor 4 is effective and safe in baboons, does not have an anticoagulant effect with excess concentration, and reverses in vivo heparin more rapidly than protamine. The data support progression to a clinical trial. (J THORAC CARDIOVASC SURG 1995;109:765-71)

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