Platelet damage by protamine and the protective effect of prostacyclin: an experimental study in dogs.

Protamine is given after cardiopulmonary bypass to reverse the effect of heparin. However, the adverse effects of an overdose have not been fully evaluated. In this canine study, a standard dose of one bolus of heparin (300 IU per kilogram of body weight) was neutralized by an infusion of protamine hydrochloride in a 1:2 ratio. Platelet number and function were severely reduced by this overdose of protamine, and this finding correlated with a prolongation of the bleeding time. Giving a titrated dose of protamine hydrochloride to reverse heparin activity, measured by the activated clotting time, affected neither platelet number nor function. When prostacyclin (0.5 microgram/kg/min) was infused during administration of an overdose of protamine, platelets again were not affected by the excess of protamine.