REVERSAL OF HEPARIN ANTICOAGULATION BY RECOMBINANT PLATELET FACTOR-4 AND PROTAMINE SULFATE IN BABOONS DURING CARDIOPULMONARY BYPASS

The ability of recombinant platelet factor 4 and protamine to neutrali ze heparin after cardiopulmonary bypass was compared in anesthestized baboons. Clotting titration curves of heparinized baboon blood demonst rate an anticoagulant effect of protamine that is not seen with recomb inant platelet factor 4. Neither drug caused meaningful changes in cen tral pressures or cardiac output within 30 minutes after injection. Af ter 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 al tered bleeding times. Recombinant platelet factor 4 caused a species-s pecific leukopenia in baboons and significantly increased activated co mplement protein 3 (C3a) more than protamine, However, the increase in plasma C3a was small and neither drug caused a significant increase i n plasma neutrophil elastase-cu, proteinase inhibitor complex, We conc lude that recombinant platelet factor 4 is effective and safe in baboo ns, does not have an anticoagulant effect with excess concentration, a nd reverses in vivo heparin more rapidly than protamine. The data supp ort progression to a clinical trial.