Platelet factor 4

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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) . This chemokine is released from alpha-granules of activated platelets during platelet aggregation, and promotes blood coagulation by moderating the effects of heparin-like molecules. Due to these roles, it is predicted to play a role in wound repair and inflammation.[1] It is usually found in a complex with proteoglycan.

Genomics

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The gene for human PF4 is located on human chromosome 4.[2]

Function

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Platelet factor-4 is a 70-amino acid protein that is released from the alpha-granules of activated platelets and binds with high affinity to heparin. Its major physiologic role appears to be neutralization of heparin-like molecules on the endothelial surface of blood vessels, thereby inhibiting local antithrombin activity and promoting coagulation. As a strong chemoattractant for neutrophils and fibroblasts, PF4 probably has a role in inflammation and wound repair.[1][3]

PF4 is chemotactic for neutrophils, fibroblasts and monocytes, and interacts with a splice variant of the chemokine receptor CXCR3, known as CXCR3-B.[4]

Clinical significance

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Antibodies

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There are a set of prothrombotic conditions caused by monoclonal antibodies against Platelet factor 4 (anti-PF4) that presents with recurrent thrombosis and persistent thrombocytopenia.[5][6] At least one author has called these Monoclonal gammopathy of thrombotic significance.

The heparin:PF4 complex is the antigen in heparin-induced thrombocytopenia (HIT), an idiosyncratic autoimmune reaction to the administration of the anticoagulant heparin.[7] PF4 autoantibodies have also been found in patients with thrombosis and features resembling HIT but no prior administration of heparin.[8]

Antibodies against PF4 have been implicated in cases of thrombosis and thrombocytopenia subsequent to vaccination with the Oxford–AstraZeneca or the Janssen COVID-19 vaccine.[9][10] This phenomenon has been termed vaccine-induced immune thrombotic thrombocytopenia (VITT).[11]

Expression changes

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Changes in the expression of PF4 have been associated with symptoms of long COVID.[12]

It is increased in patients with systemic sclerosis that also have interstitial lung disease.[13]

Malaria

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The human platelet factor 4 kills malaria parasites within erythrocytes by selectively lysing the parasite's digestive vacuole.[14]

See also

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References

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Further reading

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This article incorporates text from the United States National Library of Medicine, which is in the public domain.