Randomized trial of recombinant platelet factor 4 versus protamine for the reversal of heparin anticoagulation in humans

Background: Protamine reverses heparin anticoagulation, but it can have important side effects. We compared the safety and effectiveness of intravenous recombinant platelet factor 4 (rPF4) as an alternative to protamine in a randomized blinded trial. Methods and Results: In 81 patients having diagnostic cardiac catheterization, baseline hemodynamics were measured after a 5000-U bolus of heparin. Repeat measurements were obtained at the end of the procedure, and the anticoagulation status was determined by an activated coagulation time (ACT) and activated partial thromboplastin time (aPTT). Patients then received either protamine (50 mg IV over 10 minutes) or rPF4 (1.0 mg/kg IV over 2 minutes) in a blinded fashion. Serial measurements of hemodynamic and clotting functions were performed 5, 10, 20, and 30 minutes after drug administration. Follow up measurements and clinical assessments were made at 1, 4, 6, and 24 hours later and after 7 days. Before drug administration, ACTs, aPTTs, and hemodynamics were similar among the groups. After drug infusion, there was no difference in ACT between the protamine and rPF4 patients. At 20 and 30 minutes after drug infusion, ACT and aPTT were slightly higher in those receiving rPF4, but these changes were small and of no clinical significance. There were no clinically meaningful differences in any of the hemodynamic variables between the groups, and there were no serious side effects in any patient. Conclusions: At the dose used in this study, rPF4 was well tolerated and reversed the anticoagulant effect of heparin. These data support its continued evaluation as an alternative to protamine after cardiac surgery.