Platelet Heparin-Neutralizing Factor^[*] (Platelet Factor 4)

Summary

The heparin-neutralizing platelet factor (PF4) is released from platelets under the influence of inducers of aggregation and nucleotide-release in the form of a high-molecular weight complex. The heparin-neutralizing activity is carried by a basic protein of molecular weight 29,700, four of which combine with a proteoglycan carrier, which in turn consists of 4 chondroitin sulfate A residues and a peptide moiety.

The carrier-PF4-complex dissociates at higher ionic strength into proteoglycan and PF4 proper ; both forms (bound and free) are active in the inactivation of heparin, which displaces PF4 from its natural mucopolysaccharide carrier.

PF4 is localized in human platelets in storage organelles, most likely in the α-granules and not in the adenine nucleotide and serotonin containing dense bodies. It is released simultaneously with the contents of these latter organelles.

The physiological significance of PF4 is mainly seen in the interference with the inhibition of the clotting system by heparin within and in the vicinity of platelet aggregates. Released in circulation in the course of intravascular platelet damage, it may contribute to a facilitation of thrombin formation and action, by removing heparin.

Adequately purified PF4 does not interact with fibrinogen and its derivatives and therefore is not directly involved in the induction of intravascular coagulation or platelet aggregation.

^* Presented at the Symposium on Heparin, Basel, Switzerland, September, 1974.

• References

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