Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea.
Thromb Res. 2013 Jul;132(1):e70-5. doi: 10.1016/j.thromres.2013.05.015. Epub 2013 Jun 13.
The effects of warfarin are measured with the international normalized ratio (INR). However, the thrombin generation assay (TGA) may offer more information about global coagulation. We analyzed the monitoring performance of the TGA and INR and investigated the impact of procoagulants (fibrinogen, factor (F)II, FVII, FIX, and FX) and anticoagulants (proteins C, S, and Z) on them.
The TGA was performed on a calibrated automated thrombogram, producing lag time, endogenous thrombin potential (ETP), and peak thrombin in 239 patients treated with warfarin. Pro- and anticoagulant levels were also measured.
The INR was significantly and inversely correlated with ETP. The therapeutic range of ETP comparable to an INR range of 2.0-3.0 was 290.1-494.6. ETP showed comparable performance to the INR as a warfarin-monitoring parameter with respect to clinical complication rate. The median levels of FII, FVII, FIX, and FX and proteins C and Z tended to decrease gradually with increasing anticoagulation intensity according to the INR or ETP. Of note, protein Z levels decreased dramatically with increasing anticoagulation status. INRs were significantly determined by FII, FVII, and protein Z. ETP was significantly dependent on FVII, and proteins C and Z concentration. Protein Z significantly reduced the total amount of thrombin generation and prolonged PT value in vitro.
The INR and ETP exhibit similar efficacy for warfarin monitoring according to the clinical complication rate. Protein Z is considered to be a significant determinant of INR and ETP in patients on warfarin therapy.
华法林的效果通过国际标准化比值（INR）来衡量。然而，凝血酶生成试验（TGA）可能提供更多关于整体凝血的信息。我们分析了 TGA 和 INR 的监测性能，并研究了促凝剂（纤维蛋白原、因子（F）II、FVII、FIX 和 FX）和抗凝剂（蛋白 C、S 和 Z）对它们的影响。
在 239 名接受华法林治疗的患者中，通过校准的自动血栓图进行 TGA，生成滞后时间、内源性凝血酶潜能（ETP）和最大凝血酶。还测量了促凝和抗凝剂的水平。
INR 与 ETP 呈显著负相关。与 INR 范围 2.0-3.0 相当的 ETP 治疗范围为 290.1-494.6。ETP 作为华法林监测参数的表现与 INR 相当，与临床并发症发生率有关。根据 INR 或 ETP，FII、FVII、FIX 和 FX 以及蛋白 C 和 Z 的中位数水平逐渐降低，表明抗凝强度逐渐增加。值得注意的是，蛋白 Z 水平随着抗凝状态的增加而显著下降。INR 主要由 FII、FVII 和蛋白 Z 决定。ETP 显著依赖于 FVII 和蛋白 C 和 Z 浓度。蛋白 Z 显著减少了体外凝血酶生成的总量并延长了 PT 值。
根据临床并发症发生率，INR 和 ETP 对华法林监测的疗效相似。蛋白 Z 被认为是华法林治疗患者 INR 和 ETP 的重要决定因素。
