Heparin rebound. Studies in patients and volunteers.

Abstract

The incidence of heparin rebound was determined in 12 patients following open-heart surgery, half receiving a high dose of protamine and half a low dose, and in 6 human volunteers who received protamine based on a protamine titration. In the volunteers the average protamine dose required to neutralize exactly 3.0 mg. per kilogram of heparin was 2.71 mg. per kilogram and the average protamine-heparin ratio was 0.9. Only 1 volunteer, the 1 with the lowest protamine-heparin ratio, demonstrated heparin rebound. All patients who received the low dose of protamine (average protamine-heparin ratio 0.56) demonstrated heparin rebound within 5 hours of neutralization. In 3 cases this was associated with clinical bleeding necessitating the administration of additional protamine. None of the patients receiving the high dose of protamine (average protamine-heparin ratio 1.15) exhibited rebound. Since moderate excesses of protamine have not been shown to produce clinically important anticoagulant effects and relatively small amounts of heparin do have clinically important anticoagulant effects, it appears prudent to give enough protamine both to prevent heparin rebound and to ensure adequate neutralization.