Danaparoid

Danaparoid sodium (Orgaran) is an alternative anticoagulant that is effective for treating patients with HIT (see Chapter 13). This heparinoid consists of a depoly-merized mixture of GAGs extracted from porcine intestinal mucosa, with a mean MW of 4-7 kDa. Its components are approximately 80% low molecular weight heparan sulfate, 10% dermatan sulfate, 5% chondroitin sulfate, and a small proportion of heparan sulfate (4%) with high affinity for AT (Meuleman, 1992). Apart from the minor AT-binding heparan sulfate component, the constituents of danaparoid have a DS per monosaccharide between 0.5 and 0.7, as well as a low MW. Thus, the two important requirements to form multimolecular complexes with PF4 are not met. This is consistent with the low cross-reactivity rate of danaparoid (about 10%) (Wilde and Markham, 1997) (see Chapters 10 and 13). As danaparoid inhibits platelet activation by HIT antibodies even in the presence of heparin (Chong et al., 1989b), it is possible that the GAG mixture binds to PF4 without producing the antigen. Consequently, less PF4 is available for the small amount of higher-sulfated heparan sulfate molecules responsible for AT binding and, presumably, PF4 binding resulting in cross-reactivity with HIT antibodies (Greinacher et al., 1992).

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