Sørensen B, Ingerslev J
Center for Hemophilia and Thrombosis, Department of Clinical Biochemistry, Aarhus University Hospital, Skejby Sygehus, Denmark.
J Thromb Haemost. 2004 Jan;2(1):102-10. doi: 10.1111/j.1538-7836.2004.00528.x.
Until now, no routinely used clotting assay has demonstrated the power to reflect significantly a patient's response to recombinant factor (rF)VIIa. Adopting a thrombelastographic principle, profiles of continuous whole blood (WB) coagulation were studied in minimally altered WB activated with a small amount of tissue factor (TF). Investigation of the WB clotting profile was performed before and after ex vivo addition of rFVIIa 20 nm to WB from 26 patients with hemophilia A, two patients with severe hemophilia B, and individuals with deficiencies of FV, FX, FXI, and FXIII. In five patients with hemophilia plus inhibitors, the response to ex vivo added rFVIIa and to activated complex concentrate (APCC) was studied. Patients with severe and moderate hemophilia A demonstrated remarkable variance in the hemostatic characteristics at baseline, even in groups with the same FVIII:C activity levels. The response to rFVIIa at 20 nm also varied extensively, the effect correlating with the continuous WB coagulation phenotype at baseline. This indicates that the efficacy of rFVIIa may be optimized by tailoring the dose according to the hemostatic response to varying doses tested prior to in vivo administration. In patients with inhibitors against FVIII and factor IX, rFVIIa and APCC substitution resulted in quite similar response patterns that appeared to be dose dependent. In severe FV, FX, and FXIII-deficient WB, rFVIIa addition induced minor changes only. In FXI deficiency, rFVIIa normalized the dynamic properties of clotting, although a reduced clot firmness remained unchanged. In conclusion, the thrombelastographic analysis of WB clotting, as activated with a minute amount of TF, seems an interesting method that detects phenotypic variation amongst hemophilia patients. The method appears useful for assessment of the hemostatic capacity and it seems a promising tool for evaluation of the individual response to rFVIIa or APCC before and during in vivo administration.
到目前为止，尚无常规使用的凝血检测方法能够显著反映患者对重组因子（rF）VIIa的反应。采用血栓弹力图原理，在少量组织因子（TF）激活的轻微改变的全血（WB）中研究连续全血凝血情况。对26例甲型血友病患者、2例重度乙型血友病患者以及FV、FX、FXI和FXIII缺乏症患者的全血在体外添加20 nM rFVIIa前后进行了全血凝血谱研究。对5例血友病合并抑制剂患者，研究了其对体外添加rFVIIa和活化复合物浓缩物（APCC）的反应。重度和中度甲型血友病患者在基线时的止血特征存在显著差异，即使在FVIII:C活性水平相同的组中也是如此。对20 nM rFVIIa的反应也有很大差异，其效果与基线时的连续全血凝血表型相关。这表明，在体内给药前，根据对不同测试剂量的止血反应调整剂量，可能会优化rFVIIa的疗效。在针对FVIII和因子IX有抑制剂的患者中，rFVIIa和APCC替代导致的反应模式非常相似，且似乎呈剂量依赖性。在严重FV、FX和FXIII缺乏的全血中，添加rFVIIa仅引起微小变化。在FXI缺乏症中，rFVIIa使凝血的动态特性正常化，尽管凝块硬度降低仍未改变。总之，用微量TF激活的全血凝血的血栓弹力图分析似乎是一种有趣的方法，可检测血友病患者之间的表型差异。该方法似乎有助于评估止血能力，并且似乎是评估体内给药前和给药期间个体对rFVIIa或APCC反应的有前途的工具。
