Kremers R M W, Wagenvoord R J, Hemker H C
Romy Kremers, Oxfordlaan 70, 6224 EV, Maastricht, the Netherlands, Tel.: +31 43 388 5891, Fax: +31 43 388 4570, E-mail:
Thromb Haemost. 2014 Sep 2;112(3):486-94. doi: 10.1160/TH14-02-0172. Epub 2014 Jun 26.
Defibrination causes a ~30% decrease of thrombin generation (TG) which can be restored by adding native fibrinogen in its original concentration (3 mg/ml). The fibrinogen variant γA/γ', which binds thrombin with high affinity, is over four times more efficient in this respect than the more common γA/γA form. By using high tissue factor concentrations we accelerated prothrombin conversion so as to obtain a descending part of the TG curve that was governed by thrombin decay only. From that part we calculated the antithrombin (AT)- and α2-macroglobulin-dependent decay constants at a series of concentrations of native, γA/γA and γA/γ' fibrinogen. We found that the increase of TG in the presence of fibrinogen is primarily due to a dose-dependent decrease of thrombin inactivation by α2-macroglobulin, where the γA/γ' form is much more active than the γA/γA form. AT-dependent decay is somewhat decreased by γA/γ' fibrinogen but hardly by the γA/γA form. We assume that binding of thrombin to fibrin(ogen) interferes with its binding to inhibitors. Attenuation of decay only in part explains the stimulating effect of fibrinogen on TG, as fibrinogen stimulates prothrombin conversion, regardless of the fibrinogen variant.
去纤维蛋白作用使凝血酶生成（TG）降低约30%，通过添加原始浓度（3mg/ml）的天然纤维蛋白原可使其恢复。与凝血酶具有高亲和力的纤维蛋白原变体γA/γ'，在这方面比更常见的γA/γA形式效率高四倍以上。通过使用高组织因子浓度，我们加速了凝血酶原转化，从而获得仅由凝血酶衰变控制的TG曲线的下降部分。从该部分我们计算了在一系列天然、γA/γA和γA/γ'纤维蛋白原浓度下抗凝血酶（AT）和α2-巨球蛋白依赖性衰变常数。我们发现，在纤维蛋白原存在下TG的增加主要是由于α2-巨球蛋白使凝血酶失活的剂量依赖性降低，其中γA/γ'形式比γA/γA形式活性高得多。γA/γ'纤维蛋白原使AT依赖性衰变有所降低，但γA/γA形式几乎没有这种作用。我们假设凝血酶与纤维蛋白（原）的结合会干扰其与抑制剂的结合。衰变的减弱仅部分解释了纤维蛋白原对TG的刺激作用，因为无论纤维蛋白原变体如何，纤维蛋白原都会刺激凝血酶原转化。
