Heparin‐induced thrombocytopenia: mechanism of interaction of the heparin‐dependent antibody with platelets

Summary The interaction of the heparin‐dependent antibody with heparin and platelets has been studied using the sera and purified IgG of four patients with heparin‐induced thrombocytopenia. Both normal platelets and Bernard‐Soulier syndrome (BSS) platelets which lack glycoprotein (GP) Ib, GPV and GPIX, aggregated in response to patient serum or IgG, but only in the presence of heparin. A monoclonal antibody (Mab) against platelet Fc II receptor (IV. 3) strongly inhibited the heparin‐dependent aggregation of both normal and BSS platelets induced by patient sera/IgG. Inhibition by the anti‐GPIb Mab (AK2) was variable and occurred only with normal platelets. Anti‐GPIX Mab (FMC 25) was not inhibitory with either normal or BSS platelets. Similar results were obtained using 14 C‐serotonin release instead of platelet aggregation as a measure of platelet activation. These findings suggest that (1) the reaction of the heparin‐dependent antibody with platelets and heparin is mediated by a Fc‐dependent mechanism, (2) GPIb, GPV and GPIX are not involved in this reaction, and (3) the inhibitory effect of anti‐GPIb Mab on normal platelets is due to steric interference consistent with the platelet Fc receptor being in close proximity to GPIb.