Influence of platelet factor 4 on the neutralization of heparin by protamine

In vitro, PF4 is comparable to protamine sulfate in the neutralization of heparin, but the complexes formed with heparin are different. Even with an excess of PF4, no large PF4-heparin complexes are formed and none of the complexes are able to activate ATIII, nor do these complexes dissociate on incubation in plasma at 37 degrees C. The action of PF4 and protamine is complementary. However, excess protamine displaces PF4 or prevents its complexing with heparin. When excess protamine is used to neutralize heparin in the presence of PF4, large heparin-protamine complexes are formed incorporating PF4. In contrast to the heparin-protamine complexes formed without PF4, these do not activate ATIII nor do they dissociate on incubation. Since PF4 is liberated during ECB procedures, its contribution to the stability of heparin-protamine complexes in vivo may influence the amount of protamine needed to neutralize heparin as well as affect the reactions which have been reported on injection of protamine after ECB.