Dynamic intercellular PF4 redistribution may modulate thrombocytopenia and thrombosis immune responses in HIT. When monocytes are depleted, platelets bind more PF4, which results in severe HIT immunoglobulin G (IgG) antibody (with specificity for PF4/heparin complexes) -mediated thrombocytopenia. The amount of PF4 bound per platelet varies inversely with the WBC:platelet ratio, predominantly due to monocytes, which have a strong binding affinity for PF4. HIT antibodies potently promote prothrombotic pathways via triggering of monocyte FcγRIIA. PF4 also translocates effectively from platelets toward to the injured/inflamed endothelium that may also promote prothrombotic processes in HIT. Shuttling of PF4 from platelets toward monocytes (and perhaps endothelial cells) mitigates the degree of thrombocytopenia. Consequently, more platelets may be available in circulation for contributing to the development of thrombosis. Note: HIT antibodies also target platelet FcγRIIA, activating platelets and stimulating the release of procoagulant microparticles, which can also contribute to thrombosis. This is not depicted in the figure for simplicity. PLT, platelet.