title: Heparin neutralization by recombinant platelet factor 4 and protamine.
abstract: Protamine is the only available drug to reverse heparin-induced anticoagulation. Platelet factor 4 (PF4) is a basic polypeptide stored in platelets that reverses heparin. To investigate its potential as a reversal drug, we studied recombinant PF4 on anticoagulated blood obtained during cardiac surgery. Blood was obtained from 33 different venous reservoirs, and activated clotting time (ACT), heparin concentrations, and heparinase-ACT were determined. Anticoagulation was reversed by adding incremental PF4:heparin and protamine:heparin ratios to the heparinized blood, and the ACTs were determined (n = 21). Viscoelastic analysis of anticoagulation reversal was performed by adding protamine or PF4 at reversal ratios of 1.3:1 protamine:heparin, and 3.2:1 PF4:heparin using thromboelastography (n = 12). PF4 reversal ratios of 3:1 and 3.5:1 and protamine reversal ratios of 1:1, 1.5:1, 2:1 were not statistically different from heparinase-ACT values. There were no significant differences in viscoelastic measurements of clot formation between protamine and PF4. Recombinant PF4 at a 3.0:1 ratio reverses heparin-induced anticoagulation after cardiopulmonary bypass, and represents a potential alternative, especially for the protamine allergic patient.
authors.affiliation: Department of Anesthesiology, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: J H
authors.initials: JH
authors.lastname: Levy
authors.forename: J G
authors.initials: JG
authors.lastname: Cormack
authors.forename: A
authors.initials: A
authors.lastname: Morales
mesh_terms: D001777:Blood Coagulation / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects; D001809:Blood Viscosity; D006348:Cardiac Surgical Procedures; D002315:Cardiopulmonary Bypass; D004305:Dose-Response Relationship, Drug; D004548:Elasticity; D005340:Fibrinogen / Q000187:drug effects; D006493:Heparin / Q000008:administration & dosage / Q000097:blood; D006494:Heparin Antagonists / Q000494:pharmacology*; D019763:Heparin Lyase; D006801:Humans; D010978:Platelet Factor 4 / Q000008:administration & dosage / Q000494:pharmacology*; D011133:Polysaccharide-Lyases / Q000032:analysis; D011479:Protamines / Q000008:administration & dosage / Q000494:pharmacology*; D011994:Recombinant Proteins; D013916:Thrombelastography; D014914:Whole Blood Coagulation Time
chemical_list: D006494:Heparin Antagonists; D011479:Protamines; D011994:Recombinant Proteins; D010978:Platelet Factor 4; D005340:Fibrinogen; D006493:Heparin; D011133:Polysaccharide-Lyases; D019763:Heparin Lyase