Escobar M A, Auerswald G, Austin S, Huang J N, Norton M, Millar C M
University of Texas Health Science Center and Gulf States Hemophilia and Thrombophilia Center, Houston, TX, USA.
Klinikum Bremen-Mitte, Prof-Hess-Kinderklinik, Bremen, Germany.
Haemophilia. 2016 Sep;22(5):713-20. doi: 10.1111/hae.12954. Epub 2016 May 24.
Maintaining haemostasis in surgery is challenging for hereditary rare bleeding disorders in which multi-coagulation-factor concentrates are the only therapeutic option. Hereditary factor X (FX) deficiency affects 1:500 000 to 1:1 000 000 individuals, and no specific replacement FX concentrate has been available. A high-purity, plasma-derived FX concentrate (pdFX) has been developed for patients with hereditary FX deficiency.
Our objective was to assess the safety and efficacy of pdFX in subjects with FX deficiency undergoing surgery.
Subjects with hereditary mild-to-severe FX deficiency (basal plasma FX activity [FX:C] <20 IU dL(-1) ) undergoing surgery received pdFX preoperatively to raise FX:C to 70-90 IU dL(-1) and postoperatively to maintain levels >50 IU dL(-1) until the subject was no longer at risk of bleeding due to surgery. Efficacy of pdFX was assessed by blood loss during surgery, requirement for blood transfusion, postoperative bleeding from the surgical or other sites, and changes in haemoglobin levels. Safety was assessed by adverse events (AEs), development of inhibitors, and clinically significant changes in laboratory parameters.
Five subjects (aged 14-59 years) underwent seven surgical procedures (four major and three minor). Treatment duration was 1-15 days. For each procedure, pdFX treatment was assessed as "excellent" in preventing bleeding and achieving haemostasis. No blood transfusions were required, no AEs related to pdFX were observed, and no clinically significant trends were found in any laboratory parameters.
These data demonstrate that pdFX is safe and effective as replacement therapy in five subjects with mild-to-severe FX deficiency undergoing surgery on seven occasions.
对于遗传性罕见出血性疾病，在手术中维持止血具有挑战性，其中多凝血因子浓缩物是唯一的治疗选择。遗传性因子X（FX）缺乏症影响着1:500 000至1:1 000 000的个体，且尚无可用的特异性FX替代浓缩物。现已为遗传性FX缺乏症患者研发出一种高纯度的血浆源性FX浓缩物（pdFX）。
我们的目标是评估pdFX对接受手术的FX缺乏症患者的安全性和有效性。
患有遗传性轻至重度FX缺乏症（基础血浆FX活性[FX:C]<20 IU dL(-1)）且准备接受手术的患者在术前接受pdFX治疗，使FX:C升高至70 - 90 IU dL(-1)，术后持续用药以维持FX:C水平>50 IU dL(-1)，直至患者不再因手术而有出血风险。通过手术期间的失血量、输血需求、手术部位或其他部位的术后出血以及血红蛋白水平的变化来评估pdFX的疗效。通过不良事件（AE）、抑制剂的产生以及实验室参数的临床显著变化来评估安全性。
5名受试者（年龄14 - 59岁）接受了7次手术（4次大手术和3次小手术）。治疗持续时间为1 - 15天。对于每次手术，pdFX治疗在预防出血和实现止血方面被评定为“优秀”。无需输血，未观察到与pdFX相关的AE，且在任何实验室参数中均未发现临床显著趋势。
这些数据表明，pdFX作为替代疗法，对于7次接受手术的5名轻至重度FX缺乏症患者是安全有效的。
