Lusher J M
Division of Hematology/Oncology, Children's Hospital of Michigan, Detroit 48201, USA.
Baillieres Best Pract Res Clin Haematol. 2000 Sep;13(3):457-68. doi: 10.1053/beha.2000.0088.
The development of an inhibitor antibody to factor VIII (or factor IX) in a child with haemophilia presents a major challenge to the paediatric haematologist. This article provides an overview of the incidence of inhibitor development in early childhood (30-52% in boys with severe haemophilia A), genetic risk factors, detection, high titre, low titre and transient inhibitors, and management. Treatment of patients with inhibitors is time-consuming and expensive. One should make every attempt to ensure that the boy's family has an understanding of inhibitors, treatment options, and just what is being recommended for their child and what this involves. Immune tolerance induction is successful in approximately 85% of boys with factor VIII inhibitors, but in only 40-50% of those with factor IX inhibitors. For treatment of bleeding episodes in children with high-titre (> or = 5 Bethesda Units) inhibitors, therapeutic options include activated prothrombin complex concentrates (APCC), rF VIIa, and (for factor VIII inhibitors) porcine factor VIII. The advantages and disadvantages of each are discussed. Although factor IX inhibitors are far less common (occurring in 2-3% of boys with haemophilia B), approximately 50% are accompanied by the occurrence of anaphylaxis or severe allergic reactions to any factor IX-containing product.
血友病患儿体内出现针对凝血因子VIII（或因子IX）的抑制性抗体，这给儿科血液科医生带来了重大挑战。本文概述了幼儿期抑制性抗体产生的发生率（重度甲型血友病男孩中为30 - 52%）、遗传风险因素、检测方法、高滴度、低滴度及短暂性抑制性抗体，以及治疗方法。对有抑制性抗体的患者进行治疗既耗时又昂贵。应尽一切努力确保患儿家庭了解抑制性抗体、治疗选择，以及针对其孩子所推荐的治疗方法及其具体内容。免疫耐受诱导在约85%的有凝血因子VIII抑制性抗体的男孩中取得成功，但在有凝血因子IX抑制性抗体的男孩中成功率仅为40 - 50%。对于高滴度（≥5贝塞斯达单位）抑制性抗体患儿的出血发作治疗，治疗选择包括活化凝血酶原复合物浓缩剂（APCC）、重组凝血因子VIIa，以及（针对凝血因子VIII抑制性抗体）猪源性凝血因子VIII。文中讨论了每种治疗方法的优缺点。虽然凝血因子IX抑制性抗体远不如前者常见（在乙型血友病男孩中发生率为2 - 3%），但约50%的此类患儿会出现过敏反应或对任何含凝血因子IX的产品产生严重过敏反应。
