Mahlangu J N, Andreeva T A, Macfarlane D E, Walsh C, Key N S
Department of Molecular Medicine and Haematology, Faculty of Health Sciences, Haemophilia Comprehensive Care Centre, NHLS and University of the Witwatersrand, Johannesburg, South Africa.
City Haemophilia Center, Saint Petersburg, Russia.
Haemophilia. 2017 Jan;23(1):33-41. doi: 10.1111/hae.13108. Epub 2016 Oct 20.
Development of inhibitors to human FVIII (hFVIII) significantly complicates the control of bleeding events in patients with haemophilia A.
This prospective, multicentre, open-label, non-comparative, Phase II study evaluated the haemostatic activity of a recombinant B-domain-deleted porcine FVIII (r-pFVIII), in the treatment of non-life/non-limb-threatening bleeding in individuals with haemophilia A and FVIII inhibitors.
Acute bleeding episodes in patients with pFVIII inhibitor titres <0.8 BU mL were treated with 50 U kg body weight r-pFVIII. Those with pFVIII inhibitor titres of >0.8 BU mL received an initial calculated r-pFVIII loading dose followed by 50 U kg treatment dose. Treatment continued at 6-hourly intervals until bleeding was determined, controlled or till a maximum of eight doses was reached.
All 25 bleeding episodes in nine patients (mean age: 23.7 years; range: 14-34 years) were controlled successfully with eight or fewer injections of r-pFVIII. The median time from bleeding onset to the administration of r-pFVIII was 5.7 h (range: 1.5-20.0 h). Twenty of the bleeding episodes (80%) were controlled with one treatment dose of r-pFVIII (with or without a loading dose, median dose: 200.8 U kg ; range: 50-576 U kg ) regardless of pFVIII level. r-pFVIII was well tolerated and no treatment-emergent serious adverse events were considered by the investigator to be related to r-pFVIII administration.
The results suggest that FVIII replacement therapy with r-pFVIII could be a viable alternative to bypassing agents for the treatment of bleeding episodes in individuals with haemophilia A and FVIII inhibitors.
人FVIII（hFVIII）抑制剂的出现显著增加了A型血友病患者出血事件控制的复杂性。
这项前瞻性、多中心、开放标签、非对照的II期研究评估了重组猪B结构域缺失FVIII（r-pFVIII）在治疗有FVIII抑制剂的A型血友病患者非危及生命/肢体的出血时的止血活性。
FVIII抑制剂滴度<0.8 BU/mL的患者急性出血发作，用50 U/kg体重的r-pFVIII治疗。FVIII抑制剂滴度>0.8 BU/mL的患者先给予初始计算的r-pFVIII负荷剂量，然后给予50 U/kg的治疗剂量。每6小时给药一次，持续治疗直至出血得到确定、控制或最多达到8剂。
9例患者（平均年龄：23.7岁；范围：14 - 34岁）的所有25次出血发作均通过8次或更少次数的r-pFVIII注射成功控制。从出血开始到给予r-pFVIII的中位时间为5.7小时（范围：1.5 - 20.0小时）。无论FVIII水平如何，20次出血发作（80%）通过一剂r-pFVIII治疗（有或无负荷剂量，中位剂量：200.8 U/kg；范围：50 - 576 U/kg）得到控制。r-pFVIII耐受性良好，研究者认为没有治疗中出现的严重不良事件与r-pFVIII给药有关。
结果表明，对于有FVIII抑制剂的A型血友病患者出血发作的治疗，用r-pFVIII进行FVIII替代治疗可能是旁路制剂的一种可行替代方案。
