The Haemophilia Centre & Thrombosis Unit, Royal Free Hospital, London, UK.
J Thromb Haemost. 2010 Sep;8(9):1994-2000. doi: 10.1111/j.1538-7836.2010.03937.x.
Prothrombin time (PT) and the international normalized ratio (INR) are still routinely measured in patients with liver cirrhosis to 'assess' their bleeding risk despite the lack of correlation with the two. Thrombin generation (TG) assays are global assays of coagulation that are showing promise in assessing bleeding and thrombosis risks.
To study the relationship between the INR and TG profiles in cirrhosis-induced coagulopathy.
Seventy-three patients with cirrhosis were studied. All TG parameters were compared with those from a normal control group. Contact activation was prevented using corn trypsin inhibitor. TG was also assayed in the presence of Protac(®). The endogenous thrombin potential (ETP) ratio was derived by dividing the ETP with Protac® by the ETP without Protac®.
The INR (mean 1.7) did not correlate with the ETP and the velocity of TG (P > 0.05). There was no difference between the lag time and ETP of the two groups (P > 0.05). The velocity of TG was increased in cirrhosis (67.95 ± 34.8 vs. 45.05 ± 25.9 nM min⁻¹ ; P = 0.016) especially in patients with INRs between 1.21 and 2.0. Both the ETP with Protac(®) and the ETP ratio were increased in cirrhosis (mean 1074 ± 461.4 vs. 818 ± 357.9 nM min, P = 0.004 and 0.80 ± 0.21 vs. 0.44 ± 0.15, P ≤ 0.0001, respectively).
Despite a raised INR, TG parameters are consistent with a hypercoagulable profile in cirrhosis-related coagulopathy. This confirms that the PT or INR should not be used to assess bleeding risk in these patients, and other parameters, such as TG, need to be explored as clinical markers of coagulopathy.
尽管凝血酶原时间（PT）和国际标准化比值（INR）与肝硬化患者的出血风险缺乏相关性，但仍常规测量这些指标以“评估”其出血风险。凝血酶生成（TG）检测是评估出血和血栓形成风险的全面凝血检测，具有广阔的应用前景。
研究肝硬化诱导性凝血障碍患者的 INR 与 TG 谱之间的关系。
研究了 73 例肝硬化患者。将所有 TG 参数与正常对照组进行比较。使用玉米胰蛋白酶抑制剂预防接触激活。在存在 Protac(®)的情况下也测定 TG。通过将 Protac®的 ETP 与无 Protac®的 ETP 相除，得出 ETP 比值。
INR（平均值为 1.7）与 ETP 和 TG 速度均无相关性（P > 0.05）。两组的 lag time 和 ETP 无差异（P > 0.05）。肝硬化患者 TG 速度增加（67.95 ± 34.8 比 45.05 ± 25.9 nM min⁻¹；P = 0.016），尤其是 INR 在 1.21 至 2.0 之间的患者。用 Protac(®)处理的 ETP 和 ETP 比值在肝硬化患者中均升高（平均值分别为 1074 ± 461.4 和 818 ± 357.9 nM min，P = 0.004 和 0.80 ± 0.21 比 0.44 ± 0.15，P ≤ 0.0001）。
尽管 INR 升高，但 TG 参数与肝硬化相关凝血障碍中的高凝状态一致。这证实了 PT 或 INR 不应用于评估这些患者的出血风险，需要探索 TG 等其他参数作为凝血障碍的临床标志物。
