Livnat T, Zivelin A, Martinowitz U, Salomon O, Seligsohn U
The Amalia Biron Research Institute of Thrombosis and Hemostasis, Chaim Sheba Medical Centre, Tel Hashomer, Israel.
J Thromb Haemost. 2006 Jan;4(1):192-200. doi: 10.1111/j.1538-7836.2005.01683.x.
Recombinant factor VIIa (rFVIIa) used for the treatment of hemophilia A or B patients with an inhibitor is hemostatically effective because it induces thrombin generation (TG), despite grossly impaired FVIII- and FIX-dependent amplification of FX activation. Tissue factor (TF) and or activated platelets were shown to be essential for the rFVIIa activity.
To evaluate the relative effects of TF and phospholipids on rFVIIa-induced TG in FVIII-, FIX- and FXI-deficient plasmas.
Phospholipids had an independent effect that was augmented by TF. The contribution of blood-borne TF in FVIII-, FIX- and FXI-deficient plasma to rFVIIa-induced TG was demonstrated by removing microparticles and use of anti-TF antibodies.
At increasing concentrations of rFVIIa, the dependence of rFVIIa-induced TG on TF declined, but the presence of phospholipids was essential. rFVIIa was also shown to activate purified FIX and FX in the presence of phospholipids and absence of TF. rFVIIa-induced TG was dramatically augmented in FVIII- or FIX-deficient plasma in which the level of FVIII or FIX was increased to 1 or 2 U dL(-1).
The data indicate that rFVIIa-induced TG is affected by TF, phospholipids, rFVIIa concentration, and the presence of FVIII and FIX.
重组凝血因子VIIa（rFVIIa）用于治疗患有抑制剂的甲型或乙型血友病患者时具有止血效果，因为尽管FVIII和FIX依赖的FX激活的放大作用严重受损，但它仍能诱导凝血酶生成（TG）。组织因子（TF）和/或活化血小板被证明对rFVIIa活性至关重要。
评估TF和磷脂对FVIII、FIX和FXI缺乏血浆中rFVIIa诱导的TG的相对影响。
磷脂具有独立作用，且TF可增强该作用。通过去除微粒和使用抗TF抗体证明了FVIII、FIX和FXI缺乏血浆中血源性TF对rFVIIa诱导的TG的贡献。
随着rFVIIa浓度增加，rFVIIa诱导的TG对TF的依赖性下降，但磷脂的存在至关重要。在没有TF但有磷脂存在的情况下，rFVIIa也能激活纯化的FIX和FX。在FVIII或FIX缺乏血浆中，当FVIII或FIX水平增加到1或2 U dL（-1）时，rFVIIa诱导的TG显著增强。
数据表明，rFVIIa诱导的TG受TF、磷脂、rFVIIa浓度以及FVIII和FIX的存在影响。
