A New Approach in the Study of the Molecular and Cellular Events Implicated in Heparin-induced Thrombocytopenia

Summary

Heparin-induced thrombocytopenia (HIT), a relatively common complication of heparin therapy, results of platelet activation, via the receptor for the Fc domain of IgG (FcγRIIa), by heparin-dependentantibodies, commonly directed against the heparin-platelet factor 4 (H-PF4) antigenic complex. Our strategy was to use whole blood allowing the study of leukocyte-platelet interactions. Experiments were performed with blood from healthy donors incubated with HIT patients’ plasma and different concentrations of heparin. We showed that 75% of the HIT patients’ plasma induced the formation of leukocyteplatelet-aggregates in a heparin-dependent-manner. The formation of leukocyteplatelet-aggregates induced by HIT plasma in the presence of heparin was (i) independent of the healthy blood donor FcγRIIa polymorphism, (ii) correlated with the levels of anti H-PF₄ IgG antibodies contained in the patients’ plasma, and to a lesser extent to anti H-PF₄ IgM antibodies, and (iii) was mediated by P-selectin. This report opens new prospects in the study of the molecular and cellular events implicated in HIT.

Key words

HIT - leukocyte-platelet aggregates - P-selectin - anti H-PF₄ antibodies - FcγRIIa polymorphism

• References

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