THE EFFECTS OF HEPARINASE-1 AND PROTAMINE ON PLATELET REACTIVITY

Background: Protamine is currently the most widely used drug for the r eversal of heparin anticoagulation. Heparinase 1 (heparinase) is being evaluated as a possible alternative to protamine for the reversal of heparin anticoagulation. The authors evaluated the effects of equivale nt doses of heparinase and protamine on platelet reactivity by measuri ng agonist-induced P-selectin expression. Methods: After Institutional Review Board (IRB) approval, Informed consent was obtained from 12 he althy volunteers and 8 patients undergoing surgery requiring cardiopul monary bypass (CPB). Twenty-four ml of blood was obtained from each vo lunteer; Ih) mi of blood was obtained from each patient before the CPB , and another 10 ml was obtained, after CPB. Heparin was neutralized u sing heparinase or protamine. Platelet reactivity was assessed by meas uring the expression of P-selectin after stimulation of platelets with increasing concentrations of a thrombin receptor agonist peptide (TRA P). Data were analyzed using analysis of variance. P < 0.05 was consid ered significant. Results: For the healthy volunteers, the activated c oagulation times (ACTs) of the heparinized samples returned to baselin e values with heparinase (12.5 U/ml) or protamine (32.5 mu g/ml). For the 8 patients, the ACTs returned to baseline with heparinase (20 U/ml ) or protamine (50 mu g/ml). The authors found no difference ill the e xpression of P-selectin in samples neutralized with heparinase, but sa mples neutralized with protamine showed a significant decrease in the expression of P-selectin when compared with heparinized samples. Concl usions: At dosages that reverse the anticoagulant effects of heparin, heparinase has minimal effects on platelets, whereas platelet reactivi ty was markedly inhibited by protamine.