Résumé
Molecular heterogeneity in unfractionated heparin [UFH] and low-molecular-weight heparins [LMWHs] results in the formation of multiple complexes with platelet factor 4 [PF4] leading to the generation of heterogeneous group of antiheparin-PF4 [AHPF4] antibodies involving multiple mechanisms, which are responsible for heparin-induced thrombocytopenia [HIT] syndrome. This study evaluated the differences between the ELISA-detectable AHPF4 antibodies present in patients treated with UFH and a LMWH [Clivarin; Reviparin [R]] and the functionality of these antibodies in terms of platelet activation [mainly 14 C-serotonin release response] and its relationship with intraplatelet Ca [2+] signaling in human platelets. Plasma samples were tested for their AHPF4 antibody titer and the functionality was ascertained utilizing the functional assays of laboratory diagnosis of HIT. In a substudy, AHPF4 antibody positive samples were pooled and total IgGs [including AHPF4] were isolated. In comparison to IgGs from UFH-treated patients, LMWH-treated patients showed markedly decreased functional responses in all the HIT assays [p< 0.001]. A significantly higher increase in intraplatelet Ca [2+] mobilization was also noted in UFH group as compared to clivarin group [p < 0.01]. These results demonstrate that the functionality of AHPF4 antibodies in terms of Ca [2+] signaling could also be associated with the pathogenesis of HIT syndrome