II Medizinische Klinik und Poliklinik, Universitätsklinikum Hamburg-Eppendorf, Hamburg, Germany.
Hamostaseologie. 2012;32 Suppl 1:S48-51.
Development of FVIII inhibitors represents a major challenge in patients with mild haemophilia A (HA), because they tend to occur at an older age and classical immune tolerance induction appears to be less effective.
A man (age: 60 years) with mild HA due to the missense mutation, Leu1929Arg, received a single dose of rFVIII at 35 IU/kg prior to routine colonoscopy, totalling 25 lifetime exposure days. Two months later, rFVIII was infused for a traumatic hip haematoma. However, FVIII recovery was inappropriate, and a FVIII inhibitor of 19 BU with type-2 kinetics was detected, resulting in FVIII:C of <1%. Two weeks later, the patient experienced spontaneous iliopsoas bleeding. Parallel to bypassing therapy, we started single-agent immunosuppression with prednisolone at 1.5mg/kg. FVIII:C "normalized" at 10.2% after four weeks. After five months, the inhibitor titre fell to <0.4 BU with sustained remission after one year of follow-up.
In mild HA, FVIII inhibitors may share characteristic features with FVIII autoantibodies commonly observed in acquired HA. Therefore, immunosuppressive therapy alone could be successful at least in a subset of patients.
在轻度 A 型血友病（HA）患者中，FVIII 抑制剂的产生是一个主要挑战，因为它们往往发生在年龄较大时，而经典的免疫耐受诱导似乎效果较差。
一名 60 岁男性，因错义突变 Leu1929Arg 导致轻度 HA，在常规结肠镜检查前接受了单次剂量的 rFVIII，剂量为 35IU/kg，总共有 25 个终生暴露天数。两个月后，因髋关节血肿进行 rFVIII 输注。然而，FVIII 恢复不当，检测到 19BU 的 FVIII 抑制剂，具有 2 型动力学，导致 FVIII：C<1%。两周后，患者出现自发性髂腰肌出血。在旁路治疗的同时，我们开始使用泼尼松龙进行单药免疫抑制治疗，剂量为 1.5mg/kg。四周后，FVIII：C“正常化”至 10.2%。五个月后，抑制剂滴度降至<0.4BU，一年随访后持续缓解。
在轻度 HA 中，FVIII 抑制剂可能与获得性 HA 中常见的 FVIII 自身抗体具有共同特征。因此，单独免疫抑制治疗至少在某些患者中可能是成功的。
