Hay C R
Department of Haematology, Royal Liverpool University Hospital, England, United Kingdom.
Am J Med. 1991 Nov 4;91(5A):27S-29S. doi: 10.1016/s0002-9343(91)80145-c.
Of all nonhemophilic patients with acquired factor VIII:C (FVIII:C) inhibitors, as many as 87% suffer from hemorrhagic complications, and approximately 22% die as a result. Immunosuppressive therapy reduces or eradicates the inhibitor in 50-80% of patients, but a significant proportion remain refractory to such treatment and have a continued need for replacement therapy to manage bleeding complications. The possibility that porcine FVIII:C might fulfill this role has not been thoroughly investigated although limited data are available for patients with congenital hemophilia, which may offer some guidance. We recently reported the successful treatment with porcine FVIII:C over 2-8.5 years in five congenital hemophilia patients with high-level inhibitors initially lacking measurable cross-reactivity to porcine FVIII:C. One of four patients who developed transient, specific antiporcine inhibitors became refractory to treatment. Three further patients' antibodies demonstrated as much as 30% cross-reactivity but tolerated porcine FVIII:C therapy on demand for 18-24 months, with good clinical effect and no significant anamnesis or other untoward reactions. All five of these patients with non-cross-reacting antibodies began therapy with porcine FVIII:C and eventually lost their original inhibitors against human FVIII:C during treatment with the porcine factor. Surprisingly, when human FVIII:C was then reintroduced in three patients there was no recurrence of inhibitor activity during 3-4 subsequent years. This finding suggests that porcine FVIII:C, when administered over some interval to congenitally hemophilic patients, can induce a state of specific immune-tolerance to the human factor. On the other hand, porcine FVIII:C therapy may not suppress acquired inhibitors in nonhemophiliacs, since there is no evidence that administration of human FVIII:C causes immune-tolerance in this group. Porcine FVIII:C can be administered safely for a period of years. Anamnestic responses are unusual in acquired hemophilia, and only 20% of patients develop specific antiporcine antibodies. Porcine FVIII:C may play an important part in the long-term management of inhibitors in either congenital or acquired hemophilia.
在所有获得性凝血因子VIII：C（FVIII：C）抑制物的非血友病患者中，多达87%的患者出现出血并发症，约22%的患者因此死亡。免疫抑制治疗可使50 - 80%的患者体内抑制物减少或消除，但仍有相当一部分患者对这种治疗无效，持续需要替代治疗来控制出血并发症。尽管先天性血友病患者的相关数据有限，但猪FVIII：C能否发挥这一作用尚未得到充分研究，不过这些数据可能提供一些指导。我们最近报告了5例先天性血友病患者在2 - 8.5年期间成功接受猪FVIII：C治疗，这些患者最初对猪FVIII：C缺乏可测量的交叉反应性且存在高水平抑制物。4例产生短暂特异性抗猪抑制物的患者中有1例对治疗无效。另外3例患者的抗体显示出高达30%的交叉反应性，但按需接受猪FVIII：C治疗18 - 24个月，临床效果良好，无明显回忆反应或其他不良反应。这5例无交叉反应抗体的患者均开始接受猪FVIII：C治疗，最终在接受猪因子治疗期间失去了原来针对人FVIII：C的抑制物。令人惊讶的是，当随后在3例患者中重新引入人FVIII：C时，在随后的3 - 4年中抑制物活性未复发。这一发现表明，对先天性血友病患者在一段时间内给予猪FVIII：C，可诱导对人因子产生特异性免疫耐受状态。另一方面，猪FVIII：C治疗可能无法抑制非血友病患者的获得性抑制物，因为没有证据表明给予人FVIII：C会使该组患者产生免疫耐受。猪FVIII：C可安全给药数年。回忆反应在获得性血友病中不常见，仅20%的患者产生特异性抗猪抗体。猪FVIII：C可能在先天性或获得性血友病抑制物的长期管理中发挥重要作用。
