Image of the month - PF4 in platelets

News image of the month jan 2024 PL4 small intestine 3.JPG

Platelet factor 4 (gene: PF4) is a chemokine expressed by platelets (thrombocytes) - blood cell fragments that play a key role during blood clotting. Although its normal physiological role is not completely understood, PF4 is implicated in antimicrobial activity and life-threatening thrombosis caused by adenovirus vector covid-19 vaccines.

Platelets are cellular fragments in the blood that play a key role during wound healing. Following vascular damage, platelets become activated and aggregate to form a platelet plug that covers the damaged blood vessel walls, preventing potentially life-threatening blood loss. Although platelets are not specifically annotated in the tissue section of the HPA and the specificity categorization of the single cell type section lacks platelets, there is one platelet cell cluster included in the PBMC data of the single cell type section with relatively low gene coverage. There is also a gene cluster, including 173 genes, annotated as mainly specific to platelets with hemostasis as the main function.

A gene with very high expression in platelets is platelet factor 4 (PF4). PF4 encodes an evolutionary old chemokine with unclear function. It is thought to regulate vascular wall homeostasis by binding heparan sulfate of endothelial cells and be involved in anti-microbial defense by interacting with bacteria and viruses. PF4 is widely known for its ability to bind the anticoagulant heparin and cause heparin induced thrombocytopenia (HIT), an adverse drug effect involving anti-PF4-antibodies and uncontrolled blood clot formation. Recently, PF4 has gained interest by being implicated in a similar type of autoimmune thrombocytic side effect to covid-19 vaccines that utilizes adenovirus vectors to deliver the genetic material encoding the spike protein of SARS-CoV-2, termed vaccine-induced immune thrombotic thrombocytopenia (VITT). The immunohistochemistry staining of PF4 in the small intestine shows staining localized to the platelets within the blood vessels (brown).

Read more: Greinacher A, Warkentin TE. Platelet factor 4 triggers thrombo-inflammation by bridging innate and adaptive immunity. Int J Lab Hematol. 2023; 45(S2): 11-22.