title: Heparin-induced thrombocytopenia: further evidence for a unique immune response.
abstract: Cardiopulmonary bypass surgery (CPB) is associated with a high incidence of IgG Abs against platelet factor 4/heparin (PF4/H) complexes by day 6 after surgery. These Abs are associated with an immune-mediated adverse drug reaction, heparin-induced thrombocytopenia. Although the early onset of the anti-PF4/H IgG response is compatible with a secondary immune response, the rapid decline of Ab titers thereafter is not. To shed light on the origin of these Abs, in the present study, we prospectively compared the kinetics of these Abs with that of Abs against 2 recall Ags and to that of autoantibodies in 166 CPB patients over 4 months. Surgery induced strong inflammation, as shown by an increase in mean C-reactive protein levels. Consistent with previous studies, anti-PF4/H IgG optical density transiently increased between baseline and day 10 (P < .001; not associated with C-reactive protein levels), followed by a decrease over the next months. In contrast, concentrations of antidiphtheria toxin IgG and antitetanus toxin IgG increased constantly over the 4 months after surgery by 25%-30%. IgG autoantibodies did not change. Therefore, the transient kinetics of the anti-PF4/H IgG response resembled neither that of recall Abs nor that of IgG autoantibodies, but rather showed a unique profile.
authors.affiliation: Institute of Immunology and Transfusion Medicine, University Medicine Greifswald, 17489 Greifswald, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Pötschke
authors.forename: Sixten
authors.initials: S
authors.lastname: Selleng
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Bröker
authors.forename: Andreas
authors.initials: A
authors.lastname: Greinacher
mesh_terms: D000925:Anticoagulants / Q000009:adverse effects* / Q000276:immunology; D016824:Antigens, Human Platelet / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D016175:B-Lymphocyte Subsets / Q000276:immunology; D002097:C-Reactive Protein / Q000032:analysis; D002315:Cardiopulmonary Bypass; D002460:Cell Line; D005500:Follow-Up Studies; D006493:Heparin / Q000009:adverse effects* / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology*; D007156:Immunologic Memory; D007249:Inflammation; D010978:Platelet Factor 4 / Q000276:immunology*; D011183:Postoperative Complications / Q000139:chemically induced* / Q000276:immunology; D011446:Prospective Studies; D016553:Purpura, Thrombocytopenic, Idiopathic / Q000139:chemically induced* / Q000276:immunology
chemical_list: D000925:Anticoagulants; D016824:Antigens, Human Platelet; D001323:Autoantibodies; D001324:Autoantigens; D007074:Immunoglobulin G; D010978:Platelet Factor 4; D006493:Heparin; D002097:C-Reactive Protein