AT HIGH HEPARIN CONCENTRATIONS, PROTAMINE CONCENTRATIONS WHICH REVERSE HEPARIN ANTICOAGULANT EFFECTS ARE INSUFFICIENT TO REVERSE HEPARIN ANTIPLATETLET EFFECTS

Combined effects of heparin and protamine on plasma clot structure and platelet function were studied. Anticoagulant effects were monitored as changes in aPTT. Clot structure was defined in terms of fibrin fibe r mass/length ratio (mu) and clot elastic modulus (EM). Platelet funct ion was studied utilizing platelet aggregation and platelet force deve lopment (PFD) measurements. Heparin (1 U/ml) prolonged the aPTT from 3 0 to >300 seconds, reduced PFD from 5,100 to 0 dynes, decreased mu (in batroxobin-induced gels) from 1.36 to 1.08 X 10(13) daltons/cm and de creased clot EM from 9,600 to 2000 dynes/cm(2). Varying amounts of pro tamine reversed these effects: 16 mu g/ml normalized the aPTT, 20 mu g /ml normalized PFD, 32 mu g/ml corrected mu, and 20 mu g/ml returned E M to baseline. At high heparin concentrations (4 U/ml), protamine conc entrations which corrected anticoagulant effects were inadequate to re verse antiplatelet effects. A protamine concentration of 40 mu g/ml no rmalized the aPTT and mu, but 140 mu g/ml of protamine was required to reverse heparin suppression of force development and clot elastic mod ulus. Excess protamine inhibited clotting and platelet function. In pl asma containing 1 u heparin/ml, 140 mu g protamine/ml reduced PFD by 8 3%, prolonged the, aPTT by 63%, and reduced clot EM by 75%. In heparin free plasma, >75 mu g protamine/ml prolonged the aPTT. Thus, platelet function and clot structure are sensitive to protamine during heparin neutralization, and anti-platelet effects of heparin may persist when the aPTT is completely corrected. Excess protamine inhibits platelet function and compromises clot structure.