Morrissey J H, Macik B G, Neuenschwander P F, Comp P C
Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City 73104.
Blood. 1993 Feb 1;81(3):734-44.
Although the majority of factor VII (FVII) circulates in the zymogen form, low levels of activated factor VII (FVIIa) have been postulated to exist in plasma and to serve a priming function for triggering of the clotting cascade. However, direct measurement of plasma FVIIa has not previously been possible. We have quantified plasma FVIIa levels using a novel, highly sensitive assay that is free from interference by FVII. Specificity of this clot-based assay results from the use of a mutant tissue factor that is selectively deficient in promoting FVII activation, but retains FVIIa cofactor function. In normal adults, FVIIa was found to be present in plasma (mean: 3.6 ng/mL) with considerable variation between individuals (range: 0.5 to 8.4 ng/mL). FVIIa levels were only loosely correlated with FVII coagulant activity, but were elevated in pregnancy and reduced with oral anticoagulant therapy. Incubation of plasma on ice in glass containers (cold activation) resulted in substantial FVIIa generation. Measurement of plasma forms of factor VII is of potential clinical importance because elevated FVII coagulant activity has been implicated as a significant risk predictor for ischemic heart disease. Clinically, this new assay will now permit direct assessment of the role of plasma FVIIa in thrombotic disorders.
尽管大多数凝血因子 VII（FVII）以酶原形式循环，但据推测血浆中存在低水平的活化凝血因子 VII（FVIIa），并在触发凝血级联反应中起启动作用。然而，此前无法直接测量血浆 FVIIa。我们使用一种新型的、高度灵敏的检测方法对血浆 FVIIa 水平进行了定量，该方法不受 FVII 的干扰。这种基于凝血的检测方法的特异性源于使用了一种突变组织因子，该因子在促进 FVII 活化方面选择性缺陷，但保留了 FVIIa 辅因子功能。在正常成年人中，发现血浆中存在 FVIIa（平均值：3.6 ng/mL），个体之间存在相当大的差异（范围：0.5 至 8.4 ng/mL）。FVIIa 水平与 FVII 凝血活性仅呈弱相关，但在妊娠期间升高，口服抗凝治疗后降低。在玻璃容器中于冰上孵育血浆（冷激活）导致大量 FVIIa 生成。测量血浆形式的凝血因子 VII 具有潜在的临床重要性，因为升高的 FVII 凝血活性被认为是缺血性心脏病的重要风险预测指标。临床上，这种新的检测方法现在将允许直接评估血浆 FVIIa 在血栓形成性疾病中的作用。
