Interactions with Other Sulfated Carbohydrates

The formation of platelet-activating immune complexes is not limited to heparin (Greinacher et al., 1992, 1993). Various other sulfated polysaccharides, and even polyvinylsulfonate, bind PF4 to form antigen complexes recognized by HIT antibodies. This cross-reaction depends on their structure, especially on their DS and MW (Greinacher et al., 1992, 1995; Kelton et al., 1994; Amiral et al., 1995). In vitro assays demonstrate that pentosan polysulfate, dextran sulfate, as well as a high-sulfated chondroitin sulfate, and a highly sulfated polysaccharide (PI-88) developed for anti-tumor treatment (Rosenthal et al., 2002) can substitute for heparin. In contrast, neither dextran, dermatan sulfate, N-desulfated heparin, sulfated glucosamine (Weimann et al., 2001), nor the AT-binding pentasaccharide react in these assays. Accordingly, pentosan polysulfate, high-sulfated chondroitin sulfate, and PI-88 have induced thrombocytopenia and thrombosis in vivo (Greinacher et al., 1993; Tardy et al., 1994; Rosenthal et al., 2002). The corresponding antibodies can be detected by conventional PF4-heparin enzyme immunoassay (PF4-H EIA) demonstrating the cross-reactivity with heparin (Gironell et al., 1996).

0 0

Post a comment