DIFFERENCES IN SPECIFICITY OF HEPARIN-DEPENDENT ANTIBODIES DEVELOPED IN HEPARIN-INDUCED THROMBOCYTOPENIA AND CONSEQUENCES ON CROSS-REACTIVITY WITH DANAPAROID SODIUM

Heparin-induced thrombocytopenia (HIT) is frequently associated with a ntibodies (Abs) to heparin-PF4 complexes (H-PF4). In order to investig ate whether there are variations in specificity of Abs, we studied 63 samples from patients with suspected HIT. Two groups of samples were s eparated after comparing their reactivity against H-PF4 or recombinant PF4 (r-PF4) using ELISA. In group Abl (n=46), Abs only or mainly boun d to H-PF4 complexes and thus most of the epitopes recognized probably involved both heparin and PF4. In group Ab2 (n=17), Abs exhibited sim ilar reactivity to r-PF4 and H-PF4, and the antigens recognized were p ossibly neoepitopes mainly expressed by modified PF4 and by H-PF4 comp lexes. Platelet activation tests were positive with 56 samples contain ing high titres of Abs to H-PF4. Most samples (n=59) contained IgG ant ibodies, often associated with IgA antibodies which were more frequent ly found in group Ab2, and/or IgM. With unfractionated heparin treatme nt, HIT was associated with Ab1 or Ab2 antibodies, whereas only Abl an tibodies were detected after low-molecular-weight heparin (LMWH). Furt hermore, cross-reactivity with danaparoid sodium was present only in g roup Abl and mainly involved LMWH-treated patients.