Results of an international, multicentre pharmacokinetic trial in congenital fibrinogen deficiency
Results of an international, multicentre pharmacokinetic trial in congenital fibrinogen deficiency
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DOI：
10.1016/s0049-3848(09)70158-6
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发表时间：
2009-12-01
影响因子：
7.5
通讯作者：
Peyvandi, Flora
中科院分区：
文献类型：
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作者：
Peyvandi, Flora
罕见出血性疾病占所有遗传性凝血因子疾病的3-5%。由血浆纤维蛋白原（凝血因子I）缺乏引起的遗传性无纤维蛋白原血症仅占所有罕见出血性疾病的一小部分。无纤维蛋白原血症患者有不同的出血模式，可能包括潜在的严重或危及生命的出血。无纤维蛋白原血症的治疗旨在替代缺失的纤维蛋白原，以恢复有效的止血和止血。目前有三种纤维蛋白原来源：新鲜冷冻血浆、冷沉淀和冻干纤维蛋白原浓缩物。由于其罕见性，对无纤维蛋白原血症患者的最佳治疗知之甚少，包括纤维蛋白原浓缩物的药代动力学。为了进一步探索这一点，我们在15例无纤维蛋白原血症患者中进行了一项巴氏灭菌人纤维蛋白原浓缩物的前瞻性、开放标签、非对照、多国药代动力学试验。单次输注纤维蛋白原浓缩物（70 mg/kg体重）导致相似的纤维蛋白原抗原和活性水平，两者高度相关。输注后纤维蛋白原水平迅速升高，在1小时达到最大值约1.3 g/L。基于最大凝块硬度的替代血栓弹力图终点，纤维蛋白原浓缩物有效地恢复了凝块形成。浓缩物耐受性良好，研究期间未发生治疗相关不良事件或病毒传播证据。(C)2009爱思唯尔有限公司版权所有。
Rare bleeding disorders represent 3-5% of all inherited coagulation factor disorders. Inherited afibrinogenemia, which is caused by a deficiency in plasma fibrinogen (coagulation factor I), accounts for only a small portion of all the rare bleeding disorders. Patients with afibrinogenemia have a variable bleeding pattern that may include potentially serious or life-threatening haemorrhages. Treatment of afibrinogenemia is aimed at replacing the missing fibrinogen to restore efficient haemostasis and to stop bleeding. Three sources of fibrinogen are currently available: fresh frozen plasma, cryoprecipitate, and lyophilized fibrinogen concentrate. Owing to its rarity, little is known about the optimal treatment of patients with afibrinogenemia, including the pharmacokinetics of fibrinogen concentrate. To explore this further, we conducted a prospective, open-label, uncontrolled, multinational pharmacokinetic trial of pasteurized human fibrinogen concentrate in 15 patients with afibrinogenemia. Infusion of a single dose of fibrinogen concentrate (70 mg/kg body weight) resulted in similar fibrinogen antigen and activity levels, which were highly correlated. Fibrinogen levels rose rapidly following infusion to reach a maximum of approximately 1.3 g/L at I hour. Fibrinogen concentrate effectively restored clot formation, based on the surrogate thromboelastographic end-point of maximum clot firmness. The concentrate was well tolerated and there were no treatment-related adverse events or evidence of viral transmission during the study. (C) 2009 Elsevier Ltd. All rights reserved.