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Platelets express alloantigens that are platelet specific (eg, the HPA antigens) and alloantigens that are shared with other blood cells (eg, the ABH antigens). The blood group A and B determinants are expressed on glycolipids and on some intrinsic platelet membrane glycoproteins. This report characterizes multiple platelet proteins reacting with blood group antibodies in serum samples from mothers of children born with neonatal alloimmune thrombocytopenia. ABH antigens on additional platelet proteins are identified, including the glycosyl phosphatidylinositol-anchored protein CD109. The proteins that carry ABH antigens were identified by using monoclonal antibodies to glycoproteins Ib, IIb/IIIa, Ia/IIa, CD31, and CD109 and immunoprecipitation/immunoblotting techniques with monoclonal antibodies to A and B antigens. The maternal serum samples and anti-A and anti-B monoclonal antibodies immunoprecipitated identical radiolabeled platelet proteins including proteins at 220 and 175 kd and proteins with mobilities corresponding to glycoproteins Ib, IIb/IIIa, IV, and V. Treatment of platelets with phosphatidylinositol-specific phospholipase C released into the supernatant a 175-kd protein that expressed the blood group determinants. This protein comigrated with the glycosyl phosphatidylinositol-anchored protein CD109. When platelet proteins were purified by immunoprecipitation with monoclonal antibodies and then tested by immunoblotting, anti-A reacted with the glycosyl phosphatidylinositol-anchored protein CD109 and to glycoproteins Ib, IIb, IIa, IIIa, and CD31 (PECAM). These results indicate that structures for modification by glycosyltransferases exist on platelet CD109, which also expresses the Gov alloantigen system. This study indicates that certain platelet proteins express both platelet-specific and blood group antigens that may contribute to platelet transfusion refractoriness and to neonatal alloimmune thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is a prothrombotic disorder caused by heparin-dependent IgG (HIT-IgG) that recognizes a complex of heparin and platelet factor 4 (PF4), leading to platelet activation via the platelet Fc gammaIIa receptors (Fc gammaRIIa). Not all patients who generate HIT-IgG in response to heparin develop HIT, however, possibly because of observed differences in the ability of platelets from healthy individuals to be activated by HIT sera. It is known that a polymorphism in the platelet Fc gammaRIIa plays an important role in determining platelet reactivity to murine platelet-activating monoclonal antibodies of the IgG1 subclass: homozygous arg131 ("high responder" or HR) platelets respond well, and homozygous his131 ("low responder" or LR) platelets respond poorly, respectively, to these murine monoclonal antibodies. We sought to determine whether the differing risk for HIT among patients who receive heparin, as well as the variable platelet reactivity to HIT sera, could be explained by preferential activation by HIT-IgG of platelets bearing a particular Fc gammaRIIa phenotype. We found that the LR Fc gammaRIIa gene frequency was significantly overrepresented among 84 HIT patients, compared with that of 264 control subjects (0.565 versus 0.471; p = 0.03). We studied the subclass distribution of HIT-IgG against its major antigen, heparin/PF4 complexes, and found that 55 of 61 (90%) HIT sera expressed IgG1 antibodies either alone (n = 47) or in combination with IgG2 (n = 5) or IgG3 (n = 3). We then compared the platelet-activating profile of HIT sera with murine platelet-activating monoclonal antibodies. As expected, the murine IgG1 monoclonal antibodies preferentially activated platelets from homozygous HR individuals. In contrast, however, the LR homozygous platelets exhibited the greatest reactivity to HIT sera that contained predominantly anti-heparin/PF4 antibodies of the IgG1 subclass. We conclude that the significant overrepresentation of the LR (his131) gene among patients with HIT may be explained by the preferential activation of LR Fc gammaRIIa platelets by HIT antibodies of the IgG1 subclass, which is the predominant immunoglobulin subclass generated in HIT.