Platelet factor 4(PF4) and its multiple roles in diseases

Platelet factor 4 (PF4) combines with heparin to form an antigen that could produce IgG antibodies and participate in heparin-induced thrombocytopenia (HIT). PF4 has attracted wide attention due to its role in novel coronavirus vaccine-19 (COVID-9)-induced immune thrombotic thrombocytopenia (VITT) and cognitive impairments. The electrostatic interaction between PF4 and negatively charged molecules is vital in the progression of VITT, which is similar to HIT. Emerging evidence suggests its multiple roles in hematopoietic and angiogenic inhibition, platelet coagulation interference, host inflammatory response promotion, vascular inhibition, and antitumor properties. The emerging pharmacological effects of PF4 may help deepen the exploration of its mechanism, thus accelerating the development of targeted therapies. However, due to its pleiotropic properties, the development of drugs targeting PF4 is at an early stage and faces many challenges. Herein, we discussed the characteristics and biological functions of PF4, summarized PF4-mediated signaling pathways, and discussed its multiple roles in diseases to inform novel approaches for successful clinical translational research.