Insights into heparin-induced thrombocytopenia.
Heparin-induced thrombocytopenia (HIT) is characterized by the presence of an antibody which can activate platelets in the presence of heparin. The in vitro Ca2+ mobilization induced by purified IgG from patients with HIT was evaluated to elucidate the platelet activation mechanism in this syndrome. HIT-IgG induced platelet activation in a heparin-dependent manner. This activation was inhibited by high viscosity, consistent with a previously documented cell-cell-mediated mechanism. We found that F(ab')2 fragments from an anti-GPIIb/IIIa monoclonal antibody in some cases, and dextran sulphate or salmon sperm DNA in all cases, could substitute for heparin, suggesting that heparin exposes a neo-antigen on the platelet surface rather than serving as the primary antigen in the process. Furthermore, heparin, dextran sulphate and salmon sperm DNA all augmented the platelet activation induced by aggregated IgG, suggesting an additional charge shielding effect. These data suggest the following mechanism for platelet activation in HIT: heparin binds to the platelet surface, exposing a neoantigen which elicits an antibody response in some patients. Antibody binding in the presence of heparin leads to platelet activation through Fc receptor mediated platelet-platelet interaction, a process augmented by the charge shielding effect of heparin.
Anderson
G P
GP
Department of Internal Medicine, Ohio State University, Columbus.
D015703:Antigens, CD / Q000276:immunology; D000943:Antigens, Differentiation / Q000276:immunology; D001792:Blood Platelets / Q000378:metabolism; D002118:Calcium / Q000097:blood; D006493:Heparin / Q000009:adverse effects* / Q000276:immunology; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D015539:Platelet Activation / Q000276:immunology; D011961:Receptors, Fc / Q000276:immunology; D017452:Receptors, IgG; D013921:Thrombocytopenia / Q000139:chemically induced* / Q000276:immunology
D015703:Antigens, CD; D000943:Antigens, Differentiation; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D011961:Receptors, Fc; D017452:Receptors, IgG; D006493:Heparin; D002118:Calcium