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Platelet factor 4
Protein involved in blood clotting, wound healing and inflammation From Wikipedia, the free encyclopedia
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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.[5] It is usually found in a complex with proteoglycan.
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Genomics
The gene for human PF4 is located on human chromosome 4.[6]
Function
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.[5][7]
PF4 is chemotactic for neutrophils, fibroblasts and monocytes, and interacts with a splice variant of the chemokine receptor CXCR3, known as CXCR3-B.[8]
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Clinical significance
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Antibodies
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.[9][10] 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.[11] PF4 autoantibodies have also been found in patients with thrombosis and features resembling HIT but no prior administration of heparin.[12]
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.[13][14] This phenomenon has been termed vaccine-induced immune thrombotic thrombocytopenia (VITT).[15]
Expression changes
Changes in the expression of PF4 have been associated with symptoms of long COVID.[16]
It is increased in patients with systemic sclerosis that also have interstitial lung disease.[17]
Malaria
The human platelet factor 4 kills malaria parasites within erythrocytes by selectively lysing the parasite's digestive vacuole.[18]
See also
References
Further reading
External links
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