Pf4, also known as Platelet factor 4 or chemokine (C-X-C motif) ligand 4 (CXCL4), is a small chemokine protein synthesized from platelet α -particles. It is highly cationic and forms tetramers. PF4 is central to blood coagulation as a major physiological function, and is also involved in innate and adaptive immunity when platelets are activated in response to infections [2].

PF4 can bind to thrombopoietin receptor c -Mpl on platelets, activating the c -Mpl -JAK2 pathway, leading to phosphorylation of STAT3 and STAT5, and ultimately platelet aggregation [1].

PF4 has been extensively studied in the context of thrombotic disorders. In heparin -induced thrombocytopenia (HIT), PF4 combines with heparin to form an antigen that produces IgG antibodies. These antibodies can bind and activate cellular FcγRIIa on platelets, inducing a hypercoagulable state and thrombosis [2].

Vaccine -induced immune thrombotic thrombocytopenia (VITT), a rare complication of adenovirus vector vaccines, is also related to PF4. In VITT, anti -PF4 antibodies form immune complexes with PF4, activating platelets and neutrophils through Fc receptors [1,2]. Some studies suggest that PF4 may have multiple roles in hematopoietic and angiogenic inhibition, platelet coagulation interference, host inflammatory response promotion, vascular inhibition, and antitumor properties, though drug development targeting PF4 faces challenges due to its pleiotropic properties [2].

In conclusion, Pf4 is crucial for normal blood coagulation and immune responses. Studies related to HIT and VITT have revealed its significant role in thrombotic disorders. Understanding the functions of Pf4 through these disease -related studies helps in developing better strategies for diagnosing, treating, and preventing these thrombotic conditions.

References:

1. Buka, Richard J, Montague, Samantha J, Moran, Luis A, Watson, Steve P, Nicolson, Phillip L R. . PF4 activates the c-Mpl-Jak2 pathway in platelets. In Blood, 143, 64-69. doi:10.1182/blood.2023020872. https://pubmed.ncbi.nlm.nih.gov/37883794/

2. Liu, Zhiyan, Li, Longtu, Zhang, Hanxu, Xiang, Qian, Cui, Yimin. 2023. Platelet factor 4(PF4) and its multiple roles in diseases. In Blood reviews, 64, 101155. doi:10.1016/j.blre.2023.101155. https://pubmed.ncbi.nlm.nih.gov/38008700/

3. Greinacher, Andreas, Warkentin, Theodore E. . Thrombotic anti-PF4 immune disorders: HIT, VITT, and beyond. In Hematology. American Society of Hematology. Education Program, 2023, 1-10. doi:10.1182/hematology.2023000503. https://pubmed.ncbi.nlm.nih.gov/38066843/

4. Yang, Chieh, Wang, Irene, Chitkara, Akshit, Patel, Rushin, Kubba, Samir V. 2024. Anti-PF4 antibodies and their relationship with COVID infection. In Hematology, transfusion and cell therapy, 46, 516-523. doi:10.1016/j.htct.2023.11.012. https://pubmed.ncbi.nlm.nih.gov/38388299/

5. Cai, Zheng, Greene, Mark I, Zhu, Zhiqiang, Zhang, Hongtao. 2020. Structural Features and PF4 Functions that Occur in Heparin-Induced Thrombocytopenia (HIT) Complicated by COVID-19. In Antibodies (Basel, Switzerland), 9, . doi:10.3390/antib9040052. https://pubmed.ncbi.nlm.nih.gov/33050376/

6. Liu, Zhi-Yan, Sun, Min-Xue, Hua, Man-Qi, Xiang, Qian, Cui, Yi-Min. 2023. New perspectives on the induction and acceleration of immune-associated thrombosis by PF4 and VWF. In Frontiers in immunology, 14, 1098665. doi:10.3389/fimmu.2023.1098665. https://pubmed.ncbi.nlm.nih.gov/36926331/

7. Migita, Kiyoshi, Asano, Tomoyuki, Sato, Shuzo, Motokawa, Satoru. 2018. Induction of anti-PF4/heparin antibodies after arthroplasty for rheumatic diseases. In Fukushima journal of medical science, 64, 1-8. doi:10.5387/fms.2018-06. https://pubmed.ncbi.nlm.nih.gov/29628468/