Conclusions

From experiments with well-defined GluS, the various structural requirements for a sulfated carbohydrate to form the HIT antigen have become clear. Given this detailed knowledge, at least three carbohydrate-based anticoagulant options can be proposed that should have a negligible risk for inducing clinical HIT:

■ Mixtures of GAGs consisting predominantly of low-sulfated carbohydrates with correspondingly limited capacity to form antigenic complexes with PF4: A prototype of such an anticoagulant is danaparoid.

■ Oligosaccharides with antithrombotic activity similar to the AT-binding penta-saccharide: A prototype is fondaparinux.

■ GAGs with highly sulfated, but short, regions that are connected by nonsul-fated "spacers": a prototype is the hexadecasaccharide SR123781A (Petitou et al., 1999).

The increasing use of LMWH already seems to have reduced the incidence of HIT. We propose that the problem of HIT can be avoided further by using anticoagulants meeting the foregoing outlined criteria in our treatment arsenal.

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