A new approach in the study of the molecular and cellular events implicated in heparin-induced thrombocytopenia - Formation of leukocyte-platelet aggregates

Heparin-induced thrombocytopenia (HIT), a relatively common complication of heparin therapy, results of platelet activation, via the receptor for the Fc domain of IgC (Fc gamma RIIa), by heparin-dependent-antibodies. 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 leukocyte-platelet-aggregates in a heparin-dependent-manner. The formation of leukocyte-platelet-aggregates induced by HIT plasma in the presence of heparin was (i) independent of the healthy blood donor Fc gamma RIIa polymorphism, (ii) correlated with the levels of anti H-PF, 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.