Platelet factor 4 (PF4) is a small cytokine belonging to the CXC chemokine family that is also known as chemokine (C-X-C motif) ligand 4 (CXCL4). Chemokines play fundamental roles in the development, homeostasis, and function of the immune system, and they have effects on cells of the central nervous system as well as on endothelial cells involved in angiogenesis and angiostasis. PF4 is a 70-amino acid protein (8 kDa) that is released from the alpha-granules of activated platelets and binds with high affinity to heparin. Specifically, the active protein is a tetramer of PF4 subunits that forms a ring of heparin-binding positive charges from sites at the C-terminal region of each monomer. In contrast to other CXC chemokines, PF4 does not contain an ELR motif and lacks binding to nearly all chemokine receptors. Mouse PF4 shares 64% and 89% amino acid identity with human and rat PF4, respectively.

As a strong chemoattractant for neutrophils and fibroblasts, PF4 probably has a role in inflammation and wound repair. However, the major physiologic role of PF4 appears to be neutralization of heparin-like molecules on the endothelial surface of blood vessels, thereby inhibiting local antithrombin III activity and promoting coagulation. There can be over 100-fold higher concentrations of PF4 within clots than within normal serum. Therapeutic doses of heparin (an anticoagulant) neutralize PF4 pro-coagulant effects. The complex between heparin and PF4 can be immunogenic, producing the pathological syndrome HITT (heparin-induced thrombocytopenia and thrombosis). In addition, immunogenic complexes of PF4 with apolipoprotein H can contribute to antiphospholipid syndrome (APS).