Division of Hematology/Oncology, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA 90027, USA.
Haemophilia. 2010 May;16(3):518-24. doi: 10.1111/j.1365-2516.2009.02165.x. Epub 2009 Dec 17.
A limitation of bypassing agent therapy for haemophilia patients with inhibitors is the absence of a laboratory assay, which predicts the clinical response to treatment. Recent investigations have demonstrated the potential for thromboelastography to assess the effects of bypassing agent therapy in this patient population. While tissue factor activation has been used in several prior studies, a recent multicentre study failed to demonstrate an expected concentration-response effect of rFVIIa and called into question the tissue factor activation methods that have been employed. A comparison of kaolin to two concentrations of tissue factor as the activation method for thromboelastography was investigated in patients with haemophilia. We performed kaolin and tissue factor activated thromboelastography on blood from inhibitor and non-inhibitor patients with and without addition of rFVIIa and rFVIII. The results demonstrate that kaolin leads to a longer R, K and angle than the higher dilution of tissue factor (1:17 000) at baseline (no factor) and after addition of rFVIIa for both the inhibitor and non-inhibitor patients. Kaolin led to a longer R and K in comparison to a low dilution of tissue factor (1:42 000) following the addition of rFVIIa in the inhibitor patients. The longer R and K allows for better discrimination of the effects of rFVIIa thus making kaolin the most sensitive activation method in this setting. Thus kaolin activated thromboelastography should be considered an effective, perhaps the most effective, activator when utilizing thromboelastography to assess the effects of rFVIIa in haemophilia patients with inhibitors.
旁路制剂治疗血友病伴抑制物患者的一个局限性是缺乏预测治疗临床反应的实验室检测方法。最近的研究表明，血栓弹性描记术有可能评估该患者人群中旁路制剂治疗的效果。尽管已有几项研究使用组织因子激活，但最近的一项多中心研究未能显示 rFVIIa 的预期浓度反应效应，并对已采用的组织因子激活方法提出质疑。本研究比较了高岭土和两种浓度的组织因子作为血栓弹性描记术的激活方法，在血友病患者中进行了研究。我们对有或无 rFVIIa 和 rFVIII 加入的抑制剂和非抑制剂患者的血液进行了高岭土和组织因子激活的血栓弹性描记术检测。结果表明，与低稀释度组织因子（1:42000）相比，高岭土在基础状态（无因子）和 rFVIIa 加入后均导致 R、K 和角度更长，在抑制剂和非抑制剂患者中均如此。与低稀释度组织因子（1:42000）相比，高岭土在抑制剂患者中 rFVIIa 加入后导致 R 和 K 更长。较长的 R 和 K 使 rFVIIa 的作用更容易区分，因此使高岭土成为该环境中最敏感的激活方法。因此，在利用血栓弹性描记术评估血友病伴抑制剂患者 rFVIIa 的效果时，高岭土激活的血栓弹性描记术应被视为一种有效的、可能是最有效的激活方法。
