Johansen R F, Sørensen B, Ingerslev J
Department of Biochemistry, Centre for Haemophilia and Thrombosis, Aarhus University Hospital, Aarhus, Skejby, Denmark.
Haemophilia. 2006 Mar;12(2):190-7. doi: 10.1111/j.1365-2516.2006.01166.x.
Acquired haemophilia is a rare bleeding disorder caused by autoimmune antibodies interacting with factor VIII (FVIII) or factor IX. Anticipating a high degree of heterogeneity amongst cases, we recently initiated systematic recording of whole blood (WB) coagulation dynamic profiles using our recently developed thrombelastographic method employing very small amounts of tissue factor for activation. Six newly diagnosed patients with acquired haemophilia A in our University Hospital were investigated with the purpose to characterize the WB clotting phenotypes in each patient, as well as inspecting the ex vivo and in vivo response to supplementation with various haemostatic agents. Our results show a striking heterogeneity in patients WB clotting profiles, each patient having a particular pattern and an individual type of response to bypassing agents. Profiles in some of patients resembled severe haemophilia A, even if there was a measurable residual FVIII:C activity while others were more similar moderate-to-mild haemophilia. In one case the profile was very close to normal. Each patient seemed to respond individually to bypassing agents. WB clotting profiles assisted us in selecting an optimal treatment modality in each case and whenever possible, we compared the clinical effects of the treatment selected with the appearance of the WB clotting pattern. In one patient, the ex vivo response to FVIII looked promising, and a approximately 200 IU kg-1 per 24 h high-dose programme nearly normalized the clotting profile in 2-week time. Our preliminary small series of data should be concluded with caution. However, it seems that WB clotting profile studies at baseline, with ex vivo addition of haemostasis promoting agents, and during treatment may hold the potential to predict the success of treatment.
获得性血友病是一种罕见的出血性疾病，由自身免疫抗体与凝血因子VIII（FVIII）或凝血因子IX相互作用引起。鉴于病例之间存在高度异质性，我们最近开始使用我们新开发的血栓弹力图方法系统记录全血（WB）凝血动态图谱，该方法使用极少量的组织因子进行激活。我们对大学医院6例新诊断的获得性血友病A患者进行了研究，目的是表征每位患者的WB凝血表型，并检查对补充各种止血剂的体外和体内反应。我们的结果显示患者WB凝血图谱存在显著异质性，每位患者都有特定的模式和对旁路制剂的个体反应类型。一些患者的图谱类似于严重血友病A，即使存在可测量的残余FVIII:C活性，而其他患者则更类似于中度至轻度血友病。在一个病例中，图谱非常接近正常。每位患者似乎对旁路制剂有个体反应。WB凝血图谱有助于我们在每种情况下选择最佳治疗方式，并且只要有可能，我们就会将所选治疗的临床效果与WB凝血模式的表现进行比较。在一名患者中，对FVIII的体外反应看起来很有希望，每24小时约200 IU/kg的高剂量方案在2周内几乎使凝血图谱正常化。我们初步的小系列数据应谨慎得出结论。然而，似乎基线时的WB凝血图谱研究、体外添加促止血剂以及治疗期间可能具有预测治疗成功的潜力。
