Platelet Aggregation Following Heparin and Protamine Administration

Abstract

The effects of heparin, protamine and the heparin-protamine complex on the abilities of platelets to aggregate in vitro in response to ADP and epinephrine were determined. Citrated blood was obtained from normal [human] volunteers, and portions were treated with heparin, protamine and 3 different ratios of heparin and protamine. The threshold concentrations of ADP and epinephrine required to produce complete platelet aggregation were then determined. Compared with control citrated plasma, the geometric mean of the threshold concentration for ADP in the heparinized sample was decreased 2-fold, from 1.88 to 0.94 .mu.M; and that for epinephrine more than 3-fold, from 0.5 to 0.14 .mu.M. The threshold concentration for ADP was increased to 3.68 .mu.M in the neutralized and to 2.78 .mu.M in the overneutralized samples and that for epinephrine to 1.62 .mu.M in the neutralized and 1.82 .mu.M in the overneutralized samples. Heparin may increase the sensitivity of platelets to ADP and epinephrine as determined by platelet aggregation, and protamine added to heparinized blood not only reverses this effect, but may decrease platelet sensitivity when added in concentrations that neutralize heparin. Additional protamine has no further effect, and protamine alone has no effect on platelet aggregation.