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 IgG (FcgammaRIIa), 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 FcgammaRIIa 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.
Khairy
M
M
INSERM-U428, Faculté de Pharmacie (Université Paris V), France.
Lasne
D
D
Brohard-Bohn
B
B
Aiach
M
M
Rendu
F
F
Bachelot-Loza
C
C
D000906:Antibodies / Q000097:blood / Q000494:pharmacology; D015703:Antigens, CD / Q000235:genetics; D001792:Blood Platelets / Q000187:drug effects / Q000473:pathology; D016022:Case-Control Studies; D002448:Cell Adhesion / Q000187:drug effects; D002450:Cell Communication / Q000187:drug effects; D006493:Heparin / Q000009:adverse effects* / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007962:Leukocytes / Q000187:drug effects / Q000473:pathology; D019007:P-Selectin / Q000494:pharmacology; D010978:Platelet Factor 4 / Q000276:immunology; D011110:Polymorphism, Genetic; D017452:Receptors, IgG / Q000235:genetics; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000473:pathology*
D000906:Antibodies; D015703:Antigens, CD; C080568:Fc gamma receptor IIA; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D019007:P-Selectin; D017452:Receptors, IgG; D010978:Platelet Factor 4; D006493:Heparin