Rollin et al describe the role of IgG in modulating HIT-antibody–mediated platelet activation. (A) When plasma IgG1 (red “Y”) or IgG2 (green “Y”) bind to the platelet IgG receptor, FcγRIIA 131HH, HIT antibody (blue “Y”) binding to FcγRIIA is inhibited (black “T”). FcγRIIA is not crosslinked and platelets are not activated. (B) Plasma IgG1 binds effectively to FcγRIIA 131RR and inhibits HIT-antibody binding, but relatively more FcγRIIA receptors are left unoccupied because IgG2 binds poorly to 131RR. HIT antibodies can then bind to unoccupied receptors and crosslink them, resulting in platelet activation. The black squiggle denotes heparin or other glycosaminoglycans and the orange tetramer depicts PF4.