Low-molecular-weight heparin in patients with advanced cirrhosis
Low-molecular-weight heparin in patients with advanced cirrhosis
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DOI：
10.1111/j.1478-3231.2010.02358.x
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发表时间：
2011-01-01
影响因子：
6.7
通讯作者：
Hilgard, Philip
中科院分区：
文献类型：
--
作者：
Bechmann, Lars P.;Sichau, Matthias;Hilgard, Philip
背景和目标：由于出血并发症的风险增加，晚期肝病患者通常避免使用低分子量肝素（LMWH）。然而，许多肝功能受损的患者存在血栓形成的高风险或有抗凝治疗的指征。因此，本研究的目的是评估LMWH在肝硬化患者中的药代动力学。方法：84例连续肝硬化患者和预防性或治疗性抗凝的临床指征。根据现行指南选择LMWH剂量。在给药后4 h连续两天评估抗Xa因子活性（抗Xa）。采用Child-Turcotte-Pugh评分、MELD评分和临床特征量化肝脏疾病的严重程度，并与抗Xa值和并发症的发生相关。结果如下：抗Xa因子活性与肝脏疾病的严重程度呈负相关，抗凝血酶-III（AT）水平与抗Xa值呈正相关。AT本身与肝病严重程度呈负相关。7例患者发生静脉曲张出血。观察期间无患者死亡，未发生血栓栓塞事件。结论：肝硬化患者预防性使用LMWH似乎是安全的。血小板减少患者抗Xa值降低，与肝功能呈负相关，这挑战了在血小板减少患者中无条件使用抗Xa检测进行LMWH监测，并揭示了这些患者抗Xa分析的潜在局限性。由于肝脏合成减少，AT水平低是这种现象的最可能原因。
Background & aims: The use of low-molecular-weight heparins (LMWH) in patients with advanced liver diseases is frequently avoided because of the enhanced risk of bleeding complications. However, many patients with impaired liver function are at a high risk of thrombosis or have an indication for therapeutic anticoagulation. Therefore, the aim of this study was to evaluate the pharmacokinetics of LMWH in patients with cirrhosis. Methods: Eighty-four consecutive patients with cirrhosis and a clinical indication for prophylactic or therapeutic anticoagulation were included. The LMWH doses were chosen according to current guidelines. Antifactor Xa activity (anti-Xa) was assessed on two consecutive days, 4 h after drug administration. The severity of liver disease was quantified using Child-Turcotte-Pugh score, the MELD score and clinical features and was correlated with the anti-Xa value and the occurrence of complications. Results: Antifactor Xa activity was negatively correlated with the severity of the liver disease, and a positive correlation was observed between antithrombin-III (AT) levels and anti-Xa value. AT itself was negatively correlated with the severity of liver disease. Seven patients had an episode of variceal bleeding. No patient died during the observation interval and no thromboembolic events occurred. Conclusion: Prophylactic use of LMWH in patients with cirrhosis appears to be safe. A decreased anti-Xa value in cirrhotic patients and a negative correlation with liver function challenge the unconditional use of anti-Xa assays in LMWH monitoring in cirrhotic patients and reveals a potential limitation of anti-Xa analysis in these patients. Low levels of AT, because of reduced hepatic synthesis, are the most likely cause of this phenomenon.