Further evidence that heparin-dependent thrombocytopenia may result from Fc receptor-mediated interactions.
Heparin-dependent thrombocytopenia (HDT) and associated thrombotic complications, are thought to be linked to the appearance of anti-platelet antibodies. Attempts were made to characterize the antibodies in the sera from 10 such patients. Western blotting against platelet antigens was inconclusive, often revealing multiple bands but with considerable variability from patient to patient. An often seen band of approximately 83 kDa was also given by some nonimmune sera and the antigen appeared to be predominantly intracellular in origin. Antibodies to major membrane glycoproteins were not readily apparent. This was confirmed by the MAIPA ("Monoclonal Antibody Immobilization of Platelet Antigens") test, performed to detect antibodies to GP Ib-IX and GP IIb-IIIa. Only one weak activity to GP Ib-IX and one weak activity to GP IIb-IIIa were detected. In contrast, an antibody to the PlA1 alloantigen was readily detected in the serum of an additional patient. The ability of HDT serum to induce the aggregation of control platelets was studied in detail. Aggregation was inhibited by EDU-3, a monoclonal antibody to GP IIb-IIIa complexes, and by the synthetic peptide RGDS, suggesting an involvement of the same pathway as used by physiologic agonists. However, in agreement with Chong et al (Thromb Res 55:291, 1989), we observed that aggregation was inhibited by rabbit IgG, suggesting that it was Fc-receptor mediated. Interestingly, 2E1, a monoclonal antibody to the Fc gamma RII receptor, induced platelet aggregation with a lag phase, a characteristic of HD antibodies. Nonetheless, for different donors, there was no correlation between the length of the lag phase induced by 2E1 and HD antibodies. Fc-receptor blockade should be considered as a means for diminishing the clinical complications of HDT.
Laroche
J
J
URA 1464 CNRS, Hôpital Cardiologique, Pessac, France.
Clofent-Sanchez
G
G
Jallu
V
V
Hourdillé
P
P
Vezon
G
G
Nurden
A T
AT
D000328:Adult; D000918:Antibody Specificity; D016824:Antigens, Human Platelet / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D001327:Autoimmune Diseases / Q000139:chemically induced*; D005260:Female; D006493:Heparin / Q000009:adverse effects*; D006801:Humans; D007163:Immunosorbent Techniques; D039661:Integrin beta3; D008297:Male; D010974:Platelet Aggregation; D010980:Platelet Membrane Glycoproteins / Q000276:immunology; D011961:Receptors, Fc / Q000502:physiology*; D013915:Thrombasthenia / Q000150:complications / Q000276:immunology; D013921:Thrombocytopenia / Q000139:chemically induced*
D016824:Antigens, Human Platelet; D001323:Autoantibodies; C061248:ITGB3 protein, human; D039661:Integrin beta3; D010980:Platelet Membrane Glycoproteins; D011961:Receptors, Fc; D006493:Heparin