Michael G DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada.
Expert Rev Hematol. 2010 Oct;3(5):567-81. doi: 10.1586/ehm.10.54.
Heparin-induced thrombocytopenia (HIT) is an antibody-mediated prothrombotic disorder triggered by PF4-binding polyanions, usually heparin. The pentasaccharide anticoagulant, fondaparinux, despite its negative charge and structural similarity to heparin, does not usually promote antibody binding to PF4 (owing to absent/weak 'cross-reactivity'). Thus, despite its ability to trigger anti-PF4/heparin antibodies ('immunogenicity'), fondaparinux has low - but not zero - risk of inducing HIT de novo, or of exacerbating HIT when antibodies are already present. Indeed, despite rare reports of fondaparinux-induced HIT, this 'dissociation' between immunogenicity and cross-reactivity suggests that fondaparinux should be effective in treating HIT, as supported by several observational studies. An emerging issue: will clinicians accept this favorable experience of fondaparinux for treating HIT when a lack of randomized trials will hinder regulatory approval for this indication?
肝素诱导的血小板减少症（HIT）是一种由 PF4 结合多阴离子（通常是肝素）引发的抗体介导的血栓形成性疾病。戊多糖抗凝剂磺达肝癸钠尽管带负电荷且结构与肝素相似，但通常不会促进抗体与 PF4 结合（因为缺乏/弱“交叉反应性”）。因此，尽管磺达肝癸钠具有触发抗 PF4/肝素抗体的能力（“免疫原性”），但其引发新发性 HIT 的风险较低-但并非为零-，或在已经存在抗体时加重 HIT 的风险较低。实际上，尽管有磺达肝癸钠引起 HIT 的罕见报告，但这种免疫原性和交叉反应性之间的“分离”表明磺达肝癸钠在治疗 HIT 方面应该是有效的，这得到了几项观察性研究的支持。一个新出现的问题：当缺乏随机试验会阻碍对此适应症的监管批准时，临床医生是否会接受磺达肝癸钠治疗 HIT 的这种有利经验？
