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

Thromb Haemost. 2001 Jun;85(6):1090-6.


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.

MeSH terms

  • Antibodies / blood
  • Antibodies / pharmacology
  • Antigens, CD / genetics
  • Blood Platelets / drug effects
  • Blood Platelets / pathology
  • Case-Control Studies
  • Cell Adhesion / drug effects
  • Cell Communication / drug effects
  • Heparin / adverse effects*
  • Heparin / immunology
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin M / blood
  • Leukocytes / drug effects
  • Leukocytes / pathology
  • P-Selectin / pharmacology
  • Platelet Factor 4 / immunology
  • Polymorphism, Genetic
  • Receptors, IgG / genetics
  • Thrombocytopenia / chemically induced*
  • Thrombocytopenia / pathology*


  • Antibodies
  • Antigens, CD
  • Fc gamma receptor IIA
  • Immunoglobulin G
  • Immunoglobulin M
  • P-Selectin
  • Receptors, IgG
  • Platelet Factor 4
  • Heparin