The mechanism seems to be different but the clinical significance is not established. In the Elisa positive, aggregation negative patients, it appears that these are largely IgA mediated. These antibodies are not heparin dependent. On platelets only FcgRII is found and is of low affinity. The binding of MoAbs on FcgRII was greater on platelets from homozygous Arg donors than on platelets from homozygous His donors.
Aggregation is correlated with that binding.
The FcgRII polymorphism should be considered when antibody-dependent platelet activation or destruction is involved. There is a high thrombin generation in HIT and venous limb gangrene could be observed. HIT-IgG is a potent generation of platelet microparticles with procoagulant activity which explains the increase in thrombin generation, and strong association with venous thrombosis and syndrome of limb gangrene. Warfarin may aggravate this tendency by decreasing protein C levels without immediately having an effect on thrombin. Warfarin should be resumed until the platelets have normalized and the patient is clinically improved.