RECOMBINANT PLATELET FACTOR-4 REVERSAL OF HEPARIN IN HUMAN CARDIOPULMONARY BYPASS BLOOD

The ability of recombinant platelet factor 4, a protein of human origi n with high heparin affinity, and the present clinical heparin reversa l agent, protamine, to neutralize heparin in human whole blood was stu died by means of three standard whole blood coagulation tests: whole b lood clotting time, heparin assay, and activated clotting time. Ten su bjects were chosen at random among patients undergoing cardiopulmonary bypass operations. Heparinized blood, free of protamine, was obtained from the bypass reservoir for testing. Whole blood aliquots, without reversal agents (controls) or with either protamine (10, 20, 30, or 40 mu g/ml) or recombinant platelet factor 4 (10, 20, 40, or 80 mu g/ml) , were analyzed. The quantity of each agent required to reverse the te n samples, using 95 % upper confidence bounds (t distribution) was det ermined for each method. Recombinant platelet factor 4 reversed hepari n at 40 mu g/ml and protamine at 20 mu g/ml, suggesting a reversal rat io for recombinant platelet factor 4/protamine of 2:1 on a milligram b asis. Further, currently available methods for testing coagulation sho uld be reliable, without modification, to monitor the restoration of n ormal coagulation parameters with recombinant platelet factor 4 after cardiopulmonary bypass.