Impact of IdeS treatment on HIT antibody-mediated platelet activation. (A) HIT antibodies cause platelet activation by binding to epitopes exposed on PF4 (red tetramers) complexed with heparin (black squiggle) or platelet surface glycosaminoglycans (black, shown branching from surface proteoglycans). Once bound, the constant portion of these antibodies (Fc) binds to and activates the platelet IgG receptor, FcγRIIA (in green), resulting in platelet activation. (B) IdeS-treated antibodies are able to maintain binding to their target via the F(ab′)2 portion, but given the lack of the Fc domain, are unable to bind to FcγRIIA and activate platelets.