Synthetic pentasaccharides do not cause platelet activation by antiheparin-platelet factor 4 antibodies

A synthetic selective inhibitor of factor Xa, the pentasaccharide SR90107A/ Org31540 is in clinical development for the prophylaxis of postsurgical dee p vein thrombosis. Another synthetic pentasaccharide with even more sustain ed inhibition of factor Xa, SanOrg34006, has also been developed. Both of t hese agents were tested in comparison to unfractionated heparin and a low m olecular weight heparin (enoxaparin) for their relative platelet activation potential in heparin-induced thrombocytopenia assays. Sera from patients ( n = 30) with heparin-induced thrombocytopenia were pooled and validated for heparin-dependent aggregation responses. Using heparin-platelet factor 4 S epharose columns, antibodies to heparin-platelet factor 4 were purified fro m the same pool. The effects of heparin, enoxaparin, SR90107A/Org31540, and SanOrg34006 were evaluated in a platelet aggregation assay using platelet donors (n = 10). At comparable concentrations, heparin and enoxaparin consi stently produced platelet activation, whereas both pentasaccharides failed to produce a response at a concentration up to 100 mu g/mL (similar to 50 m u M) Similarly, in the C-14-serotonin release and flow cytometric assays, h eparin and enoxaparin produced positive responses (n = 30), whereas the two pentasaccharides consistently failed to produce any effect. These observat ions suggest that the two pentasaccharides with highly selective anti-Xa ac tivity are devoid of generating antiheparin-platelet factor 4 antibody, do not produce heparin-induced thrombocytopenic responses and may inhibit acti ve heparin-induced thrombocytopenia antibody platelet activation.