CHARACTERIZATION OF THE HUMORAL IMMUNE-RESPONSE IN HEPARIN-INDUCED THROMBOCYTOPENIA

Recent reports indicate that antibodies associated with heparin-induce d thrombocytopenia and thrombosis (HITP) are specific for complexes fo rmed between heparin and the heparin-binding, platelet alpha granule p rotein, platelet factor 4 (PF4). As with other disorders mediated by i mmune complexes (IC), the characteristics of the involved immunoglobul ins could affect the ability of IC to cause symptoms. We therefore stu died the class, subclass, and potency of antibodies specific for hepar in:PF4 complexes formed by two groups of patients: one with severe thr ombocytopenia, with or without thrombosis, and a positive serotonin re lease assay (SRA) (Group 1) and another with mild or absent thrombocyt openia, absence of thrombosis, and a negative SRA despite having forme d antibodies reactive with heparin:PF4 complexes (Group 2). IgG antibo dies were more common in the Group 1 patients (100%) than in Group 2 ( 46%), whereas IgM antibodies were more common in Group 2 (81%) than in Group 1 (42%) (P = 0.009). About half of each group formed IgA antibo dies. In each group, the IgG antibodies were predominantly IgG1 (82%); 42% were IgG3. Only one IgG2 antibody was identified in a total of 52 antibody formers. Antibodies of the IgG class were consistently of hi gher titer in Group 1 patients than in Group 2 patients (P < 0.001). R ecent reports suggest that the H131 form of the Fc gamma RII receptor, which binds preferentially to lgG2 Pc, is found with greater than exp ected frequency in patients with HITP. Identification of only one IgG2 antibody among 38 antibodies of the IgG class argues against a unique role for antibodies of this subclass in the pathogenesis of HITP. The finding that titers of antibodies in Group 1 patients were a signific antly higher titer than in Group 2 patients suggests that development of the full-blown HITP syndrome may require the formation of antibodie s of unusually high titer. (C) 1997 Wiley-Liss, Inc.