Inhibition of the cerebroside sulphate (sulphatide)-induced contact activation reactions by platelet factor four

Abstract

Cerebroside sulphate or sulphatides, present in erythrocyte and leucocyte cell membranes, have recently been shown to be a potent activator of the contact phase of coagulation. Platelet factor-four (PF4), purified from human washed platelets, was found to inhibit the sulphatide induced APTT and plasma prekallikrein activation in a dose dependent manner. A four-fold increase in the sulphatide-APTT was observed at 156pM PF4 in the reaction mixture and 30% inhibition of prekallikrein activation was observed at 1.6nM. PF4 was found to be an approximately 1000-fold more potent inhibitor than protamine sulphate in inhibiting activation of clotting but was not as potent in inhibiting activation of prekallikrein. The physiological form of PF4 as released from platelets, was also found to cause inhibition of plasma prekallikrein activation, with 50% inhibition observed when the concentration of PF4 in plasma was 2.25 g/ml (0.29 M). The ability of PF4 to inhibit the contact activation reactions induced by sulphatides may be of some physiological significance in that when released during platelet activation and vessel wall injury, it may have a protective effect against the development of thrombosis.