Université de Lyon, F-42023, Saint-Etienne, France.
Thromb Res. 2012 Dec;130(6):925-8. doi: 10.1016/j.thromres.2012.07.025. Epub 2012 Oct 15.
Protein S (PS) is an essential component of the protein C pathway and PS deficiency can explain a poor response to activated protein C. It has recently been shown that PS also acts as a cofactor of Tissue Factor Pathway Inhibitor (TFPI).
In the present study, we investigated whether PS deficiency could be responsible for a poor response to TFPI.
PATIENTS/METHODS: Thirty-one patients with inherited PS deficiency, seven pregnant women and 36 controls were enrolled in the study. We measured the plasma response to added TFPI using a two-step diluted prothrombin time (dPT) assay. The response of the different plasmas to the anticoagulant activity of TFPI was expressed as TFPI Normalised Ratio (TFPI NR).
The median TFPI NR was statistically significantly lower in patients with inherited PS deficiency (0.5) than in controls (1.0) (p<0.0001). It was statistically significantly lower in patients with type I inherited PS deficiency (0.47) compared to patients with type III inherited PS deficiency (0.58) (p=0.018). In contrast, it did not differ between patients with and without thrombosis. Median TFPI NR values were statistically significantly lower during pregnancy (0.54) than 3 months after delivery (0.71) (p=0.016). TFPI NR values correlated well with PS activity values (R(2)=0.681) whatever the nature of the PS deficiency.
Our findings confirm that PS deficiency results in a poor anticoagulant response to TFPI, demonstrating again the cofactor role of PS in TFPI activity.
蛋白质 S（PS）是蛋白 C 途径的重要组成部分，PS 缺乏可导致蛋白 C 激活后的反应不佳。最近的研究表明，PS 还可作为组织因子途径抑制物（TFPI）的辅助因子。
本研究旨在探讨 PS 缺乏是否可导致 TFPI 反应不佳。
患者/方法：31 例遗传性 PS 缺乏症患者、7 例孕妇和 36 例对照者纳入研究。采用两步稀释凝血酶原时间（dPT）检测法测量添加 TFPI 后血浆的反应。不同血浆对 TFPI 抗凝活性的反应以 TFPI 归一化比值（TFPI NR）表示。
遗传性 PS 缺乏症患者的中位 TFPI NR 显著低于对照组（0.5 比 1.0）（p<0.0001）。与 III 型遗传性 PS 缺乏症患者（0.58）相比，I 型遗传性 PS 缺乏症患者（0.47）的 TFPI NR 显著降低（p=0.018）。然而，TFPI NR 与血栓形成与否无关。与产后 3 个月（0.71）相比，妊娠期的中位 TFPI NR 值显著降低（0.54）（p=0.016）。无论 PS 缺乏的类型如何，TFPI NR 值与 PS 活性值均呈良好相关性（R2=0.681）。
本研究结果证实 PS 缺乏可导致 TFPI 抗凝反应不佳，再次证明 PS 在 TFPI 活性中作为辅助因子的作用。
