For The Prevention Or Treatment Of

The fact that heparin's molecular size determines its platelet-binding affinity and capacity and its ability to assemble ultralarge complexes with PF4 explains why LMWH preparations are associated with a lower incidence of HIT than standard UFH and why, in some instances, LMWH has been given to patients with HIT without adverse consequences (Warkentin et al., 1995; Slocum et al., 1996). Indeed, there is increasing evidence that the very smallest heparin, the synthetic pentasac-charide, fondaparinux (Mr 1728), may be a promising medication for patients with HIT (Elalamy et al., 1995; Walenga et al., 1997) (see Chapter 17). Although fondaparinux apparently can bind well enough to PF4 to be immunogenic and the anti-PF4-heparin antibodies identified in patients who have received this drug can promote platelet activation in vitro in the presence of UFH or LMWH, they are not active in the presence of fondaparinux (Warkentin et al., 2005). In theory, this is because fondaparinux is either too small to form a stable complex with PF4 or to mediate the binding of complexes to the platelet surface (Elalamy et al., 1995; Walenga et al., 1997; Ahmad et al., 1999; Warkentin et al., 2005).

Similarly, the safety and efficacy of treating HIT patients with danaparoid, a so-called heparinoid, can be explained by the fact that its major component (approximately 84% heparan sulfate) does not bind to platelets (Horne, 1988; Magnani, 1993). On the other hand, danaparoid sometimes cross-reacts with HIT antibodies in laboratory tests for HIT (see Chapter 13). This is perhaps mediated by a minor component of danaparoid (about 12% dermatan sulfate) that does have weak affinity for both platelets and PF4 (Barber et al., 1972; Horne, 1988).

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