VIII 因子升高可增强因子 VIII 缺乏、因子 XI 缺乏或磺达肝癸钠存在时的凝血酶生成。
Elevated factor VIII enhances thrombin generation in the presence of factor VIII-deficiency, factor XI-deficiency or fondaparinux.
机构信息
Department of Anesthesiology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
出版信息
Thromb Res. 2011 Feb;127(2):135-40. doi: 10.1016/j.thromres.2010.10.017. Epub 2010 Dec 8.
BACKGROUND
Increased levels of factor VIII occur as a response to vascular injury and/or inflammation, and may increase thrombotic risks. In contrast, factor VIII deficiency poses a major hemostatic challenge. The role of factor VIII in modulating hemostasis/thrombosis was investigated in plasma models of hypocoagulable and hypercoagulable state using thrombin generation (TG) assay.
METHODS
TG was performed in undiluted/diluted control, FVIII-deficient, FVIII-deficient with low antithrombin (AT activity, ~59%), and factor XI-deficient plasma samples using relipidated tissue factor (TF, 2 pM) or dilute Actin as activators. The impact of elevated FVIII on TG was simulated by adding Humate-P (0 to 3 U/ml) to the above plasma samples. In fondaparinux (1 μg/ml) treated plasma with normal or lower AT activity effects of Humate-P vs. 60 nM of recombinant activated factor VII (rFVIIa) were also evaluated.
RESULTS
Humate-P increased TG concentration dependently in undiluted and diluted control plasma with TF activation. With Actin activation, only the concentration dependent shortening of lag time, but no change in peak thrombin was observed. In FVIII-deficient, FVIII-deficient with low AT, and FXI-deficient samples, 3 U/ml of Humate-P increased TG, and decreased its onset with either activator. The reduced peak thrombin due to fondaparinux was reversed with Humate-P (3 U/ml) more than with rFVIIa. Elevated FVIII levels seem to favor intrinsic tenase formation and antagonize fondaparinux because anti-FIXa aptamer added to fondaparinux effectively attenuated TG.
CONCLUSION
Elevated FVIII supports the propagation of TG via intrinsic tenase formation under low TF condition, factor XI deficiency or in the presence of fondaparinux.
背景
VIII 因子水平升高是血管损伤和/或炎症的反应，可能会增加血栓形成的风险。相比之下，VIII 因子缺乏会带来严重的止血挑战。本研究使用血栓生成（TG）检测，在低抗凝酶（AT）活性（~59%）的 VIII 因子缺乏和 VIII 因子缺乏的血浆模型中，研究了 VIII 因子在调节止血/血栓形成中的作用。
方法
使用重新酯化组织因子（TF，2 pM）或稀释的 Actin 作为激活剂，在未稀释/稀释的对照、VIII 因子缺乏、VIII 因子缺乏伴低 AT 活性和因子 XI 缺乏的血浆样本中进行 TG 检测。通过向上述血浆样本中添加 Humate-P（0 至 3 U/ml）来模拟升高的 VIII 因子对 TG 的影响。在正常或较低 AT 活性的 fondaparinux（1 μg/ml）处理的血浆中，还评估了 Humate-P 与 60 nM 重组活化因子 VII（rFVIIa）的作用。
结果
Humate-P 以浓度依赖的方式增加 TF 激活的未稀释和稀释对照血浆中的 TG 浓度。用 Actin 激活时，仅观察到滞后时间的浓度依赖性缩短，而峰值凝血酶没有变化。在 VIII 因子缺乏、低 AT 的 VIII 因子缺乏和因子 XI 缺乏的样本中，3 U/ml 的 Humate-P 增加了 TG，并降低了两种激活剂的起始时间。由于 fondaparinux 导致的峰值凝血酶减少被 Humate-P（3 U/ml）逆转，比 rFVIIa 更有效。升高的 VIII 因子水平似乎有利于内在凝血酶原酶的形成，并拮抗 fondaparinux，因为添加到 fondaparinux 中的抗 FIXa 适体有效减弱了 TG。
结论
在低 TF 条件下、因子 XI 缺乏或存在 fondaparinux 时，升高的 VIII 因子通过内在凝血酶原酶的形成支持 TG 的传播。
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