Rocino A, Papa M L, Salerno E, Capasso F, Miraglia E, de Biasi R
Divisione di Ematologia, Centro Emofilia e Trombosi, Ospedale San Giovanni Bosco, Napoli, Italy.
Haemophilia. 2001 Jan;7(1):33-8. doi: 10.1046/j.1365-2516.2001.00461.x.
Inhibitor antibodies to transfused factor VIII pose significant challenges in the management of haemophilia A patients. The main concern is the inefficacy of replacement therapy in patients with high-titre antibodies, who have a shorter life-span and a greater morbidity compared to subjects without inhibitors. The ultimate goal in treating these patients is to eliminate the inhibitor antibody entirely, allowing the recommencement of specific replacement therapy. The results of an immune tolerance regimen based on pharmacokinetic parameters are reported here. In 12 high-responder haemophilia A patients immune tolerance induction (ITI) was attempted with daily administration of factor VIII concentrates of very high purity, either plasma-derived or produced by recombinant-DNA technology. Patients were given 100 IU kg(-1) day(-1) until the inhibitor was shown to be absent by at least two negative assays 1 month apart, with normal recovery of infused factor VIII and normal half-life (> 6 h), as assessed after a 3-day washout period. After the patient was judged to be inhibitor-free, immune tolerance treatment was continued with unmodified factor VIII doses for 2 months. Doses were thereafter gradually reduced and finally, regular prophylaxis by administration of 25 IU kg(-1) three times weekly was instituted. Immune tolerance was achieved in 10 of the 12 patients (including six of seven with long-standing inhibitors) within a median time of 8 months. Outcome of immune tolerance was not influenced by age at start of ITI nor by the interval between inhibitor development and ITI. The success rate and the inhibitor disappearance time of our immune tolerance regimen, utilizing high-purity factor VIII, agrees with those reported by other investigators.
针对输入的凝血因子 VIII 的抑制性抗体给甲型血友病患者的治疗带来了重大挑战。主要问题在于，对于高滴度抗体患者，替代疗法无效，与无抑制剂的患者相比，他们的寿命更短，发病率更高。治疗这些患者的最终目标是完全消除抑制性抗体，从而能够重新开始特异性替代疗法。本文报告了基于药代动力学参数的免疫耐受方案的结果。在 12 例高反应性甲型血友病患者中，尝试采用每日给予高纯度凝血因子 VIII 浓缩物进行免疫耐受诱导（ITI），这些浓缩物要么是血浆源性的，要么是通过重组 DNA 技术生产的。患者按 100 IU kg⁻¹ 天⁻¹ 的剂量给药，直到通过至少两次间隔 1 个月的阴性检测显示抑制剂不存在，且输注的凝血因子 VIII 恢复正常，半衰期正常（> 6 小时），这是在 3 天洗脱期后评估得出的。在判定患者无抑制剂后，继续用未调整的凝血因子 VIII 剂量进行免疫耐受治疗 2 个月。此后逐渐减少剂量，最后开始每周三次给予 25 IU kg⁻¹ 的常规预防治疗。12 例患者中有 10 例（包括 7 例有长期抑制剂的患者中的 6 例）在中位时间 8 个月内实现了免疫耐受。免疫耐受的结果不受 ITI 开始时的年龄影响，也不受抑制剂出现与 ITI 之间间隔的影响。我们使用高纯度凝血因子 VIII 的免疫耐受方案的成功率和抑制剂消失时间与其他研究者报告的结果一致。
