Platelet Factor 4 (PF4), a chemokine stored in platelet α-granules, plays roles in coagulation and inflammation. PF4 antibodies, particularly IgG class, are central to heparin-induced thrombocytopenia (HIT), a prothrombotic disorder triggered by heparin therapy. In HIT, heparin binds PF4. forming complexes that trigger IgG antibody production. These antibodies activate platelets via Fcγ receptors, causing thrombosis and platelet consumption.
Recently, PF4 antibodies gained attention in vaccine-induced immune thrombotic thrombocytopenia (VITT), a rare complication linked to adenoviral vector COVID-19 vaccines (e.g., AstraZeneca). Unlike HIT, VITT occurs without heparin exposure. Antibodies in VITT directly target PF4. inducing platelet activation and thrombosis through similar Fcγ receptor pathways, though the initial trigger remains unclear.
PF4 antibody detection involves ELISA (to identify anti-PF4/heparin antibodies) and functional assays (e.g., serotonin-release assay) to confirm platelet-activating capacity. However, not all PF4-reactive antibodies are pathogenic; clinical correlation is essential.
Research continues to explore why only some individuals develop pathogenic PF4 antibodies, focusing on genetic, immunological, and structural factors. Understanding these mechanisms is critical for improving diagnostics and therapies for antibody-mediated thrombotic disorders.