MASSIVE FACTOR-VIII INFUSION IN HÆMOPHILIAC WITH FACTOR-VIII INHIBITOR, HIGH RESPONDER
MASSIVE FACTOR-VIII INFUSION IN HÆMOPHILIAC WITH FACTOR-VIII INHIBITOR, HIGH RESPONDER
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血友病患者大量输注 VIII 因子抑制剂，反应良好
DOI：
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发表时间：
1977
期刊：
影响因子：
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通讯作者：
J. Gormsen
中科院分区：
文献类型：
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作者：
H. Brackmann;J. Gormsen
使用低反应型凝血因子VIII抑制剂的血友病患者的出血通常通过大量凝血因子VIII输注来克服。免疫抑制治疗的增加可能是成功的高反应，延迟和可能削弱回忆反应。“活化"因子IX浓缩物也可能有用。然而，这些方案是不合适的，当长期的替代治疗是必要的高反应。我们的病人是一个20岁的血友病患者，有因子VIII抑制剂。他的哥哥，也是一个有抑制剂的血友病患者，18岁死于腹膜后出血。我们的病人自出生以来就有出血发作，在30多次住院治疗中多次输注全血、血浆、冷沉淀物和凝血因子VIII浓缩物，但都没有取得多大成功。在他12岁的时候检测到了抑制物。他曾三次接受浓缩物联合免疫抑制治疗，最后一次（1973年）是环磷酰胺（15 mg/kg静脉注射，随后2 mg/kg体重口服，持续10天），4-5天后抑制剂浓度从0.55单位/ml增加到2周后30-40单位/ml的峰值。2个月后恢复到输注前水平。1976年，18岁的他出色地通过了最后的学校考试，但他被限制在轮椅或床上，他想更加独立。这将需要长时间的物理治疗，只有在消除抑制剂后由因子VIII覆盖才能实现。我们决定使用波恩嗜血中心提供的治疗方法-每日大量输注因子VIII和活化因子IX，直到输注后抑制剂的增加被消除，之后每日剂量应保持抑制剂水平较低并允许物理治疗。我们的病人在波恩接受治疗。入院时，他的凝血因子VIII水平为1%，抑制剂水平为0.5 Bethesda单位/ml。剂量和抑制剂水平如图所示。起初，他每天接受3000单位的因子VIII和2500单位的浓缩因子IX。他的抑制物水平在第一周内增加至约1100单位/ml，直到他接受12 000单位/天的因子VIII治疗10天后才显著下降。然后可以减少剂量，每天注射3个月后，获得1单位/ml的抑制剂水平。3周后，抑制剂浓度升高，因子VIII的日剂量减少太多，但当剂量增加时，抑制剂浓度再次下降。7个月后，他在每天服用3000单位的因子VIII和1000单位的因子IX浓缩物（“Feiba”）时没有可证实的抑制剂。由于feiba短缺，他收到了其他IX因子浓缩物。e e e e
Sir,—Bleeding in hæmophiliacs with factor-VIII inhibitors of low-responder type is generally overcome by massive factor-VIII infusions. The addition of immunosuppressive therapy may be successful in high responders, delaying and possibly weakening the anamnestic response. ‘‘Activated’’ factor-IX concentrates may also be useful. These regimens, however, are unsuitable when prolonged substitution therapy is necessary in a high responder. Our patient is a 20-year-old hæmophiliac with factor-VIII inhibitor. His elder brother, also a hæmophiliac with inhibitor, died aged 18 from a retroperitoneal hæmorrhage. Our patient has had bleeding episodes since birth and has been given many infusions of whole blood, plasma, cryoprecipitate, and factor-VIII concentrates in more than thirty hospital admissions, without much success. Inhibitor was detected when he was 12 years old. Three times he has received concentrates in combination with immunosuppressive therapy, the last (1973) being with cyclophosphamide (15 mg/kg intravenously followed by 2 mg/kg body-weight orally for 10 days) when the inhibitor concentration increased after 4–5 days from 0Æ5 units/ml to a peak of 30–40 units/ml after 2 weeks. The preinfusion level was regained after 2 months. In 1976 at the age of 18 he passed his final school examination, brilliantly, but he was confined to a wheelchair or bed and he wanted to be more independent. This would need prolonged physiotherapy, which could be achieved only if covered by factor-VIII after elimination of inhibitor. We decided to use the treatment given by the hæmophilic centre in Bonn —a combination of daily massive infusions of factor VIII and activated factor IX until the increase in inhibitor, which follows infusions, has been eliminated, after which daily doses should keep the inhibitor level low and permit physiotherapy. Our patient was treated in Bonn. His factor-VIII level was 1% and his inhibitor level was 0.5 Bethesda units/ml on admission. The dosages and inhibitor levels are shown in the figure. At first he received 3000 units of factor VIII and 2500 units of concentrated factor IX daily. His inhibitor level increased during the first week to about 1100 units/ml and did not fall significantly until he had received 12 000 units of factor VIII per day for 10 days. The dose could then be reduced, and after 3 months with daily injections an inhibitor level of 1 unit/ml was obtained. The inhibitor concentration rose 3 weeks later, the daily dosage of factor VIII having been reduced too far, but the inhibitor concentration fell again when the dose was increased. After 7 months he has no demonstrable inhibitor while on 3000 units of factor VIII and 1000 units of factor IX concentrate (‘Feiba’) daily. He received, due to shortage of feiba, other factor-IX concentrates in between. E E E E T E E E E EE E E bleeding E = elbow T = thigh