Proposed schematic representation of the interaction of HIT IgG and normal IgG subclasses with platelets according to the FcγRIIA H131R polymorphism. (A) In FcγRIIA HH–immunized patients, IgG2 (green) and IgG1 (dark blue) may bind to FcγRIIA receptors (blue). This interaction thereby reduces the ability of HIT IgG (red) associated with PF4/H complexes to bind via their Fc fragment in either cis (intraplatelet) or trans (interplatelet) FcγRIIA receptors at a sufficient extent to activate platelets. (B) In FcγRIIA RR–immunized patients, IgG2 are not able to bind platelet FcγRIIA receptors, which therefore remain available to cross-link with a larger number of HIT IgG-PF4/H ICs, inducing more potent platelet activation with the release of larger amounts of phospholipid procoagulant microparticles. Together with enhanced synthesis of TF, this effect probably explains the higher risk of thrombosis in patients homozygous for the FcγRIIA R allele.