Lak M, Scharling B, Blemings A, Sharifian R, Maleki Z, Daraee A, Arjmand A R, Hedner U
Iranian Haemophilia Centre, Iman Khomeini Hospital, Tehran University of Medical Science, Tehran, Iran.
Haemophilia. 2008 Jan;14(1):103-10. doi: 10.1111/j.1365-2516.2007.01592.x. Epub 2007 Dec 7.
Glanzmann thrombasthenia (GT) is a rare platelet function disorder characterized by a defect in fibrinogen binding to platelet membrane glycoprotein (GP) IIb/IIIa. Recombinant FVIIa (rFVIIa) is a haemostatic agent approved for the treatment of haemophilia patients with inhibitors, patients with acquired haemophilia and in EU also for treatment of factor VII (FVII)-deficient patients and GT patients with antibodies to GPIIb-IIIa. The present study was conducted to evaluate the use of the whole blood test system, rotational thrombelastometry (ROTEM), in measuring the overall haemostasis potential of rFVIIa in 28 GT patients treated with rFVIIa. The correlation of administered rFVIIa and time to start fibrin formation and clot dynamic/stability was assessed and correlation to the clinical response was elucidated. Assessments were performed on predose blood samples spiked with four different concentrations of rFVIIa and whole blood samples taken at 10 and 120 min following dosing. ROTEM parameters clotting time (CT), clot formation time (CFT) and maximum clot firmness (MCF) were measured. Both ex vivo and in vivo data showed beneficial effects on CT in the presence of rFVIIa, but no effect of added rFVIIa was seen on CFT and MCF. In conclusion, the use of thrombelastography at least in the modified form of ROTEM seems to be of limited use in predicting an adequate dose of rFVIIa in GT patients. A good clinical haemostatic response was recorded in spite of the limited changes in the ROTEM pattern supporting the conclusion that ROTEM should not be the method of choice for monitoring rFVIIa therapy in Glanzmann patients.
Glanzmann血小板无力症（GT）是一种罕见的血小板功能障碍，其特征是纤维蛋白原与血小板膜糖蛋白（GP）IIb/IIIa结合存在缺陷。重组凝血因子VIIa（rFVIIa）是一种止血剂，已被批准用于治疗有抑制剂的血友病患者、获得性血友病患者，在欧盟还可用于治疗凝血因子VII（FVII）缺乏症患者以及对GPIIb-IIIa有抗体的GT患者。本研究旨在评估全血检测系统——旋转血栓弹力图（ROTEM）在测量28例接受rFVIIa治疗的GT患者中rFVIIa的整体止血潜力方面的应用。评估了给予的rFVIIa与开始形成纤维蛋白的时间以及凝块动态/稳定性之间的相关性，并阐明了与临床反应的相关性。对添加了四种不同浓度rFVIIa的给药前血样以及给药后10分钟和120分钟采集的值来血样进行评估。测量了ROTEM参数凝血时间（CT）、凝块形成时间（CFT）和最大凝块硬度（MCF）。体外和体内数据均显示在存在rFVIIa的情况下对CT有有益影响，但未观察到添加的rFVIIa对CFT和MCF有影响。总之，至少以改良形式的ROTEM进行血栓弹力图检查在预测GT患者中rFVIIa的合适剂量方面似乎用途有限。尽管ROTEM模式变化有限，但仍记录到良好的临床止血反应，这支持了ROTEM不应作为监测Glanzmann患者rFVIIa治疗的首选方法这一结论。
