Schematic representation of the mechanism of how PF4 mediates antibacterial host defense and concurrently primes for HIT. Bacteria activate platelets, which release positively charged PF4 interacting with polyanions at the bacterial surface. This generates clusters of PF4, which initiate antibody production by B cells. Once antibodies are induced, they can bind to all bacterial strains, which form PF4 clusters on their surface. Antibody binding to PF4-coated bacteria facilitates binding to granulocytes and subsequently phagocytosis. On the other hand, these antibodies can induce a severe adverse drug reaction, HIT. During heparin treatment, heparin binds to platelets. This mediates formation of PF4/heparin complexes on the platelet surface. These platelet/PF4/heparin complexes mimic PF4 bound to bacteria, and the anti-PF4/polyanion antibodies bind to the platelet surface by their Fab part where they activate platelets by crosslinking the platelet Fc-receptors with their Fc parts. This finally results in massive thrombin generation via a cascade involving activated platelets, platelet microparticles, endothelial cells, and monocytes leading to HIT and new thrombosis. Yellow circles, brown rods, and violet rectangles represent different bacterial species.