Dynamic model of platelet activation by HIT IgG.

(1) Complexes of PF4–heparin form on the surfaces of weakly activated platelets. (2) HIT IgG binds to the platelet-bound PF4–heparin through the Fab region. (3) The Fc portion of the bound IgG cross-links FcγRII on the same (not illustrated) or adjacent platelets and produces strong platelet activation. (4) PF4, released from the activated platelets, forms more complexes with heparin on platelets and promotes antibody binding. In this model, blocking FcγRII with IV.3 would still permit the Fab part of IgG to bind platelets, but IV.3 would inhibit platelet activation.