Carbohydrates A Interactions with LMWHs

Generation of the HIT antigen depends not only on the concentration, but also on the chain length of heparin. LMWH preparations (Table 2) have reduced affinity for platelets, endothelial cells, and plasma proteins, such as PF4 (Horne, 1993; O'Brien et al., 1985; Turpie, 1996). Accordingly, LMWHs are less likely to form multimolecular complexes with PF4 (Greinacher et al., 1993; Rauova et al., 2005). Hence, LMWHs are less likely than UFH to induce an immune response, resulting in a lower frequency of HIT (Warkentin et al., 1995; Greinacher et al., 2005; Martel et al., 2005; Warkentin et al., 2006b).

Despite their lower immunogenicity, LMWHs exhibit nearly 100% in vitro cross-reactivity to HIT antibodies using sensitive assays (Greinacher et al., 1994b,c; Warkentin et al., 1995; Amiral et al., 1996b; Amiral, 1997). The small variations found with different LMWH preparations in vitro are probably based on their individual composition of molecules with different chain length (Fareed et al., 1988). Homogeneous heparin molecules consisting of 20, 18, 16, 14, and 12 monosaccharides form antigenic multimolecular complexes to which HIT antibodies bind strongly. Fragments containing 10 residues form complexes with PF4 which are recognized by the antibodies only weakly as judged by platelet-activation assay, while fragments containing eight and six residues are even less reactive (Amiral et al., 1995; Greinacher et al., 1995) or non-reactive (Visentin et al., 2001).

0 0

Post a comment