K. Fijnvandraat, MD PhD, Emma Children's Hospital, Academic Medical Center, Room number H7-228, PO Box 22660, 1100 DD Amsterdam, The Netherlands, Tel.: +31 20 566 2727, Fax: +31 20 566 9683, E-mail: c.
Thromb Haemost. 2015 Jul;114(1):46-55. doi: 10.1160/TH14-11-0940. Epub 2015 Apr 16.
In nonsevere haemophilia A (HA) patients the presence of an inhibitor may exacerbate the bleeding phenotype dramatically. There are very limited data on the optimal therapeutic approach to eradicate inhibitors in these patients. We aimed to describe inhibitor eradication treatment in a large cohort of unselected nonsevere HA patients with inhibitors. We included 101 inhibitor patients from a source population of 2,709 nonsevere HA patients (factor VIII 2-40 IU/dl), treated in Europe and Australia (median age 37 years, interquartile range (IQR) 15-60; median peak titre 7 BU/ml, IQR 2-30). In the majority of the patients (71 %; 72/101) the inhibitor disappeared; either spontaneously (70 %, 51/73) or after eradication treatment (75 %, 21/28). Eradication treatment strategies varied widely, including both immune tolerance induction and immunosuppression. Sustained success (no inhibitor after rechallenge with factor VIII concentrate after inhibitor disappearance) was achieved in 64 % (30/47) of those patients rechallenged with FVIII concentrate. In high-titre inhibitor patients sustained success was associated with eradication treatment (unadjusted relative risk 2.3, 95 % confidence interval 1.3-4.3), compared to no eradication treatment. In conclusion, in nonsevere HA patients most inhibitors disappear spontaneously. However, in 35 % (25/72) of these patients an anamnestic response still can occur when rechallenged, thus disappearance in these patients does not always equal sustained response. Treatment for those requiring eradication has to be decided case by case, as one single approach is unlikely to be appropriate for all.
在非重度血友病 A (HA) 患者中，抑制剂的存在可能会显著加重出血表型。关于这些患者消除抑制剂的最佳治疗方法，仅有非常有限的数据。我们旨在描述大量未选择的非重度 HA 伴抑制剂患者的抑制剂消除治疗。我们纳入了来自 2709 例非重度 HA 患者（VIII 因子 2-40IU/dl）源人群中的 101 例抑制剂患者，这些患者在欧洲和澳大利亚接受治疗（中位年龄 37 岁，四分位间距 [IQR] 15-60；中位峰值效价 7BU/ml，IQR 2-30）。在大多数患者（71%，72/101）中，抑制剂消失了；要么是自发的（70%，51/73），要么是经过消除治疗后（75%，21/28）。消除治疗策略差异很大，包括免疫耐受诱导和免疫抑制。在接受因子 VIII 浓缩物再挑战后，有 64%（30/47）的患者在抑制剂消失后获得了持续成功（在抑制剂消失后再次接受因子 VIII 浓缩物挑战时没有抑制剂）。在高滴度抑制剂患者中，与未进行消除治疗相比，持续成功与消除治疗相关（未调整的相对风险 2.3，95%置信区间 1.3-4.3）。总之，在非重度 HA 患者中，大多数抑制剂会自发消失。然而，在这些患者中有 35%（25/72）的患者在再次接受挑战时仍会发生记忆反应，因此这些患者的消失并不总是等于持续反应。对于需要消除治疗的患者，必须根据具体情况决定治疗方案，因为不太可能有一种方法适用于所有患者。
