Zeitler Heike, Ulrich-Merzenich Gudrun, Panek Darius, Goldmann Georg, Vidovic Natascha, Brackmann Hans-Hermann, Oldenburg Johannes
Internal Medical Clinic I, Center of Extracorporeal Therapy and Autoimmunity (CETA), Germany.
Transfus Med Hemother. 2012 Aug;39(4):264-270. doi: 10.1159/000341913. Epub 2012 Jul 26.
In acquired hemophilia (AH), autoantibodies (inhibitors) impede blood coagulation factors leading to severe bleedings. Cornerstones of a successful treatment are the control of bleeding and an eradication of autoantibodies. The present study is an update of our previous documentation of the treatment of high-titer AH patients with severe life-threatening bleeding undergoing the modified Bonn-Malmö-Protocol (MBMP). METHODS: 64 AH patients were treated by a standard combination protocol (MBMP) consisting of antibody depletion through immunoadsorption, i.v. immunoglobulin, immunosuppression, and high-dose FVIII substitution. They underwent a long-term follow-up. RESULTS: Primary study endpoints loss of detection of the activity of the inhibitor and FVIII recovery ? 5% were reached in a median time of 3 days (95% CI: 2.6-3.4 days), the median time of FVIII substitution was 13 days (95% CI 10.6-15.3 days), and the median time of immunoadsorption was 16 days (95% CI 13-18.9 days). In 5 patients the AH occurred as paraneoplastic syndrome, and partial remission was achieved. Relapses without bleeding event occurred only in second-line MBMP. Those responded excellently to short time treatment. Overall patients remained in remission over a median follow-up time of 8 years. Conclusion: Except for paraneoplastic AH, MBMP-treated patients have a remarkable prognosis which is confirmed by long-term follow-up with a complete response rate of 93% (53/57) in the first year post MBMP and 100% during long-term follow-up. These outcome in life-threatening AH is unique and until now not achievable via other treatment schedules. In life-threatening bleedings physicians should take into account MBMP as a first line treatment.
在获得性血友病（AH）中，自身抗体（抑制物）会阻碍血液凝固因子，导致严重出血。成功治疗的关键在于控制出血和消除自身抗体。本研究是我们之前关于采用改良波恩 - 马尔默方案（MBMP）治疗伴有严重危及生命出血的高滴度AH患者的文献更新。方法：64例AH患者接受了标准联合方案（MBMP）治疗，该方案包括通过免疫吸附清除抗体、静脉注射免疫球蛋白、免疫抑制以及高剂量FVIII替代。他们接受了长期随访。结果：主要研究终点，即抑制物活性检测不到且FVIII恢复≥5%，中位时间为3天（95%置信区间：2.6 - 3.4天），FVIII替代的中位时间为13天（95%置信区间10.6 - 15.3天），免疫吸附的中位时间为16天（95%置信区间13 - 18.9天）。5例患者的AH表现为副肿瘤综合征，并实现了部分缓解。仅在二线MBMP治疗中出现无出血事件的复发。这些患者对短期治疗反应良好。总体而言，患者在中位随访时间8年期间保持缓解状态。结论：除副肿瘤性AH外，接受MBMP治疗的患者预后显著，长期随访证实了这一点，MBMP治疗后第一年的完全缓解率为93%（53/57），长期随访期间为100%。这种危及生命的AH的治疗结果是独特的，迄今为止通过其他治疗方案无法实现。在危及生命的出血情况下，医生应将MBMP作为一线治疗方案考虑。
