Synthetic pentasaccharides do not cause platelet activation by antiheparin-platelet factor 4 antibodies
Synthetic pentasaccharides do not cause platelet activation by antiheparin-platelet factor 4 antibodies
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DOI：
10.1177/107602969900500410
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发表时间：
1999-10-01
影响因子：
2.9
通讯作者：
Fareed, J
中科院分区：
文献类型：
--
作者：
Ahmad, S;Jeske, WP;Fareed, J
作为Xa因子的合成选择性抑制剂，五糖SR90107A/Org31540正处于临床开发阶段，用于预防术后深静脉血栓形成。另一种对Xa因子具有更持久抑制作用的合成五糖SanOrg34006也被开发出来。在肝素诱导的血小板减少试验中，这两种药物与未分离肝素和低分子量肝素（依诺肝素）的相对血小板活化电位进行了比较。收集肝素诱导的血小板减少症患者（n = 30）的血清，验证肝素依赖性聚集反应。使用肝素-血小板因子4 Sepharose柱，从同一池中纯化肝素-血小板因子4抗体。采用血小板供体（n = 10）进行血小板聚集试验，评估肝素、依诺肝素、SR90107A/Org31540和SanOrg34006的作用。在相同浓度下，肝素和依诺肝素一致产生血小板活化，而两种五糖在浓度高达100 μ g/mL（类似于50 μ M）时均未能产生反应。同样，在c -14- 5 -羟色胺释放和流式细胞分析中，肝素和依诺肝素产生阳性反应（n = 30），而两种五糖一致未能产生任何作用。这些观察结果表明，具有高选择性抗xa活性的两种五糖不产生抗肝素-血小板因子4抗体，不产生肝素诱导的血小板减少反应，并可能抑制活性肝素诱导的血小板减少抗体血小板活化。
A synthetic selective inhibitor of factor Xa, the pentasaccharide SR90107A/Org31540 is in clinical development for the prophylaxis of postsurgical deep vein thrombosis. Another synthetic pentasaccharide with even more sustained inhibition of factor Xa, SanOrg34006, has also been developed. Both of these agents were tested in comparison to unfractionated heparin and a low molecular 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 Sepharose columns, antibodies to heparin-platelet factor 4 were purified from 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 consistently produced platelet activation, whereas both pentasaccharides failed to produce a response at a concentration up to 100 mu g/mL (similar to 50 mu M) Similarly, in the C-14-serotonin release and flow cytometric assays, heparin and enoxaparin produced positive responses (n = 30), whereas the two pentasaccharides consistently failed to produce any effect. These observations suggest that the two pentasaccharides with highly selective anti-Xa activity are devoid of generating antiheparin-platelet factor 4 antibody, do not produce heparin-induced thrombocytopenic responses and may inhibit active heparin-induced thrombocytopenia antibody platelet activation.