Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
J Thromb Haemost. 2012 Aug;10(8):1581-90. doi: 10.1111/j.1538-7836.2012.04790.x.
Tissue factor pathway inhibitor (TFPI) is the major inhibitor of tissue factor-initiated coagulation, making it an interesting and novel therapeutic target in hemophilia treatment. The aptamer BAX499 (formerly ARC19499) is designed to improve hemostasis by specifically inhibiting TFPI.
The aim of the study was to examine the concentration-dependent augmentation of clotting by BAX499.
Whole blood clot formation was quantified by rotational thromboelastometry and thromboelastography, and thrombin generation in platelet-poor plasma was assessed with the calibrated automated thrombogram, in samples from patients with congenital hemophilia A (N=55) and B (N=11), patients with acquired hemophilia A (N=1), and healthy controls (N=37).
BAX499 significantly improved clotting of samples from hemophilic patients in a concentration-dependent manner, resulting in clotting profiles in samples from patients with severe hemophilia that were similar to those of healthy controls.
BAX499 improved ex vivo clotting parameters in blood and plasma from patients with hemophilia A and B with different severity of disease, and also in a patient with acquired hemophilia. These results further support the contention that anti TFPI strategies may be an effective treatment for hemophilic patients.
组织因子途径抑制剂（TFPI）是组织因子引发的凝血的主要抑制剂，使其成为血友病治疗中一个有趣且新颖的治疗靶点。适体 BAX499（前称 ARC19499）旨在通过特异性抑制 TFPI 来改善止血。
本研究旨在检查 BAX499 的浓度依赖性增强凝血作用。
通过旋转血栓弹性测定法和血栓弹性图定量测定全血凝块形成，通过校准自动血栓图评估血小板缺乏的血浆中的凝血酶生成，在来自先天性血友病 A（N=55）和 B（N=11）患者、获得性血友病 A 患者（N=1）和健康对照者（N=37）的样本中进行。
BAX499 以浓度依赖性方式显著改善了血友病患者样本的凝血，导致严重血友病患者样本的凝血谱与健康对照者相似。
BAX499 改善了来自不同疾病严重程度的血友病 A 和 B 患者的血液和血浆中的体外凝血参数，也改善了获得性血友病患者的凝血参数。这些结果进一步支持了抗 TFPI 策略可能是血友病患者有效治疗方法的观点。
