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凝血酶生成可衡量急性肝损伤和急性肝衰竭时凝血的再平衡。

Evidence of rebalanced coagulation in acute liver injury and acute liver failure as measured by thrombin generation.

机构信息

Department of Haematological Medicine, King's Thrombosis Centre, London, UK.

出版信息

Liver Int. 2014 May;34(5):672-8. doi: 10.1111/liv.12369. Epub 2013 Nov 20.

Abstract

BACKGROUND & AIMS: Patients with liver disease often show profound abnormalities in their haemostatic system. Studies using thrombin generation demonstrate rebalanced coagulation in patients with chronic liver disease. Our aim was to evaluate the haemostatic profile in patients with acute liver injury/failure (ALI/ALF) compared with healthy controls.

METHODS

Thrombin generation was measured in the presence and absence of thrombomodulin (TM) to activate protein C (PC) with endogenous thrombin potential (ETP; the area under the thrombin generation curve) a key parameter. Routine coagulation assays were also performed.

RESULTS

Thirty two patients with ALI/ALF and 40 controls were recruited. Patients had grossly abnormal coagulation profiles with decreased pro- and anticoagulant factors compared with controls (P < 0.001 for all comparisons), except for median Factor VIII which was increased 247 U/dl [interquartile range: 214-347] in patients compared with 120 U/dl [97-139; P < 0.001] in controls. Mean ETP was significantly lower in patients 886 nM.min (± 436) compared with controls 1596 nM.min (± 259; P < 0.001). However, when the assay was repeated with TM to activate PC, there was no significant difference in mean ETP + TM between patients and controls (632 ± 418 vs 709 ± 301 nM.min respectively; P = 0.666). Furthermore, the ETP ratio (ETP + TM/ETP) was significantly higher in patients 0.89 (0.60-0.97) compared with controls 0.48 (0.3-0.6; P = 0.002) and negatively correlated with PC (R = -0.487, P = 0.003) and Factor V (R = -0.431, P = 0.01).

CONCLUSION

ALI/ALF patients have normal ETP in the presence of TM. This supports rebalanced coagulation mediated by acquired PC resistance because of the reduction in PC, Factor V and concomitant increase in Factor VIII.

摘要

背景与目的

患有肝脏疾病的患者其止血系统通常会出现明显异常。使用凝血酶生成研究表明,慢性肝脏疾病患者的凝血得到了再平衡。我们的目的是评估与健康对照组相比,急性肝损伤/衰竭(ALI/ALF)患者的止血特征。

方法

使用血栓调节蛋白(TM)激活蛋白 C(PC)来测量凝血酶生成,以生成凝血酶生成曲线的面积(关键参数)作为内源性凝血酶潜能(ETP)。还进行了常规凝血检测。

结果

共纳入 32 名 ALI/ALF 患者和 40 名对照者。与对照组相比,患者的凝血谱严重异常,促凝和抗凝因子均降低(所有比较均 P < 0.001),但中位数VIII因子除外,患者为 247 U/dl [四分位距(IQR):214-347],而对照组为 120 U/dl [97-139;P < 0.001]。与对照组相比,患者的平均 ETP 明显更低 886 nM.min(± 436)与 1596 nM.min(± 259;P < 0.001)。然而,当使用 TM 重复该检测以激活 PC 时,患者和对照组之间的平均 ETP + TM 无显著差异(分别为 632 ± 418 与 709 ± 301 nM.min;P = 0.666)。此外,患者的 ETP 比值(ETP + TM/ETP)明显更高 0.89(0.60-0.97)与对照组相比 0.48(0.3-0.6;P = 0.002),并与 PC(R = -0.487,P = 0.003)和因子 V(R = -0.431,P = 0.01)呈负相关。

结论

AL/ALF 患者在存在 TM 的情况下 ETP 正常。这支持了凝血的再平衡,这是由 PC、因子 V 的减少以及因子 VIII 的同时增加导致的获得性 PC 抵抗介导的。

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