title: Reversal of heparin anticoagulation by recombinant platelet factor 4 and protamine sulfate in baboons during cardiopulmonary bypass.
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 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-alpha 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.
authors.affiliation: Harrison Department of Surgery, School of Medicine, University of Pennsylvania, Philadelphia, USA.
authors.forename: A
authors.initials: A
authors.lastname: Bernabei
authors.forename: N
authors.initials: N
authors.lastname: Gikakis
authors.forename: T E
authors.initials: TE
authors.lastname: Maione
authors.forename: M A
authors.initials: MA
authors.lastname: Kowalska
authors.forename: Z
authors.initials: Z
authors.lastname: Yan
authors.forename: S
authors.initials: S
authors.lastname: Niewiarowski
authors.forename: L H
authors.initials: LH
authors.lastname: Edmunds
mesh_terms: D000818:Animals; D001780:Blood Coagulation Tests; D002315:Cardiopulmonary Bypass; D005260:Female; D006494:Heparin Antagonists / Q000494:pharmacology*; D010215:Papio; D010978:Platelet Factor 4 / Q000494:pharmacology*; D011479:Protamines / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors
chemical_list: D006494:Heparin Antagonists; D011479:Protamines; D011994:Recombinant Proteins; D010978:Platelet Factor 4