FIGURE 5 Dissociation in immunogenicity and cross-reactivity: comparison of UFH, LMWH, and fondaparinux. Of the three sulfated polysaccharide anticoagulants, UFH is most immunogenic (largest iceberg), whereas LMWH and fondaparinux exhibit similar immunogenicity. However, in contrast to UFH and LMWH, which can form well the antigens recognized by HIT antibodies, fondaparinux only poorly forms antigens with PF4 in vitro that are recognized by HIT antibodies. (Note: LMWH is indicated by ++ and ++++ to indicate that its cross-reactivity appears to differ in vivo [++] and in vitro [++++].) Abbreviations: HIT, heparin-induced thrombocytopenia; HIT-T, HIT-associated thrombosis; LMWH, low molecular weight heparin; UFH, unfractionated heparin. Source: From Warkentin, 2006b.

these antibodies could represent a surrogate marker for another key risk factor, such as inflammation—a known risk factor for atherosclerosis-associated mortality (Ridker et al., 1997). This distinction is critical: if these antibodies are truly pathogenic ("forme fruste HIT"), avoiding heparin might be beneficial, whereas this is unlikely to be the case if the antibodies are merely a marker for other vascular risk factors (Warkentin and Sheppard, 2006b).

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