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- W1523770901 abstract "Heparin-induced thrombocytopenia (HIT), is a unique model of immune-mediated disorder due to the development of antibodies (mainly IgG) specific to platelet factor 4 (PF4). PF4 is a C-X-C chemokine present in platelet alpha granules and released in plasma as tetramers that exposed an electropositive ring critical for the binding of heparin, a negatively-charged molecule. PF4-heparin interactions induce the expression of neoepitopes involving several aminoacids (including P37, R49, L55 and K61) and responsible for the humoral immune response associated with HIT that requires helper T-cells and immunoglobulin class switching. Thrombocytopenia and thrombotic complications are likely to result from a multicellular activation involving platelets, endothelial cells, and monocytes. Platelet activation is mediated by the binding of HIT-IgG present within large multimolecular immune complexes to FcgammaRIIa receptors. This interaction leads to platelet activation, granule release and the generation of procoagulant phospholipid-rich microparticles. HIT antibodies might also activate endothelium by interacting with PF4-heparan sulfate complexes. Recently, a PF4-dependent binding of HIT IgG to monocytes inducing a tissue factor synthesis was also demonstrated and this mechanism likely contributes to the generation of thrombin associated with HIT and resulting thrombotic events. The treatment of HIT depending on this physiopathology is based on the replacement of heparin by drugs (danaparoid sodium or hirudin) that poorly or does not crossreact with antibodies to PF4. The risk of HIT is higher in conditions associated with a strong platelet activation such as cardiopulmonary bypass and in patients who are treated by unfractionated heparin, mixture of glycosaminoglycans containing large amounts of chains exceeding ten monosaccharides with a high degree of sulfation. The risk of HIT is therefore lower with low-molecular weight heparins and might be further reduced in the future with the use of synthetic pentasaccharide." @default.
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- W1523770901 date "2002-10-11" @default.
- W1523770901 modified "2023-09-28" @default.
- W1523770901 title "Pathogenesis of heparin-induced thrombocytopenia" @default.
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