Potential role of activated neutrophils based on our and other published data. Region left of the dashed line shows the situation prior to heparin infusion. Here, PF4 is bound to the surface of vascular cells. Heparin infusion (right of the dashed line) results in PF4-heparin complexes in blood and immune response. Platelets and neutrophils may be activated via 3 modes based on results in this paper and other published data^4,11,12 : PF4–anti-PF4 complexes formed on platelet/neutrophil surface chondroitin sulfates may activate either the same cell (mode A) or an adjacent cell (mode B) via CD32a. In addition, PF4–heparin–anti-PF4 immune complexes formed in solution may ligate CD32a and trigger cell activation in both cells (mode C). Platelet activation results in release of α-granule content including PF4, amplification of cell activation processes, and thrombocytopenia. Neutrophil activation results in degranulation of secondary and tertiary granules and up-regulation of cell surface Mac-1. Newly expressed P-selectin on platelets and functionally active Mac-1 on neutrophils likely contribute to new adhesive interactions in the vasculature. These may include neutrophil-platelet adhesion, enhanced neutrophil-endothelial interactions, or neutrophil-neutrophil secondary interactions that amplify leukocyte-endothelial cell-binding events.