Kalambokis Georgios N, Oikonomou Aikaterini, Baltayiannis Gerasimos, Christou Leonidas, Kolaitis Nikolaos I, Tsianos Epameinondas V
1st Division of Internal Medicine, Medical School.
Hematology Laboratory Unit of Molecular Biology, Medical School.
Hepatol Res. 2016 Mar;46(3):E36-44. doi: 10.1111/hepr.12520. Epub 2015 May 22.
Hypercoagulability has been detected in patients with cirrhosis yet its clinical significance remains unclear. We investigated the association of hypercoagulability with clinical outcomes in patients with cirrhosis.
Thrombin-antithrombin (TAT) complexes as thrombin generation (TG) marker, D-dimer, antithrombin (AT), protein C, protein S, international normalized ratio (INR), activated partial thromboplastin time, fibrinogen, Child-Pugh class and Model for End-Stage Liver Disease (MELD) were evaluated. Two different multivariate analyses were performed: one not including MELD (model 1) and one including MELD and excluding INR (model 2).
Eighty-one patients (Child-Pugh class A/B/C: 27/27/27) and 40 healthy subjects were enrolled. Only ΤΑΤ and AT were independently associated with increasing liver disease severity. Increased TAT levels and MELD score were significantly associated with ascites and varices at baseline. Independent predictors of follow-up events were: TAT and MELD score for new-onset ascites; TAT and AT for variceal bleeding (VB); TAT and AT for portal vein thrombosis (PVT); and TAT and MELD for mortality. TAT equaled MELD in mortality prediction at 12 and 18 months. TAT cut-offs at 5.35, 14.6, 13.5 and 9.25 ng/mL identified patient groups with significantly higher probability of new-onset ascites, VB, PVT and mortality, respectively.
Increased TG is strongly correlated with portal hypertension-related complications, PVT and mortality in patients with cirrhosis. Measuring TG by TAT could enable risk stratification and institution of preventive strategies to improve clinical outcomes.
已在肝硬化患者中检测到高凝状态，但其临床意义仍不明确。我们研究了肝硬化患者高凝状态与临床结局之间的关联。
评估了凝血酶 - 抗凝血酶（TAT）复合物作为凝血酶生成（TG）标志物、D - 二聚体、抗凝血酶（AT）、蛋白C、蛋白S、国际标准化比值（INR）、活化部分凝血活酶时间、纤维蛋白原、Child - Pugh分级和终末期肝病模型（MELD）。进行了两种不同的多变量分析：一种不包括MELD（模型1），另一种包括MELD并排除INR（模型2）。
纳入了81例患者（Child - Pugh分级A/B/C：27/27/27）和40名健康受试者。仅TAT和AT与肝病严重程度增加独立相关。基线时，TAT水平升高和MELD评分与腹水和静脉曲张显著相关。随访事件的独立预测因素为：新发腹水的TAT和MELD评分；静脉曲张出血（VB）的TAT和AT；门静脉血栓形成（PVT）的TAT和AT；以及死亡率的TAT和MELD。在12个月和18个月时，TAT在死亡率预测方面与MELD相当。TAT临界值分别为5.35、14.6、13.5和9.25 ng/mL时，分别确定了新发腹水、VB、PVT和死亡概率显著更高的患者组。
肝硬化患者中TG升高与门静脉高压相关并发症、PVT和死亡率密切相关。通过TAT测量TG可实现风险分层并制定预防策略以改善临床结局。
