Vahtera Annukka, Vaara Suvi, Pettilä Ville, Kuitunen Anne
Tampere University Hospital, Critical Care Medicine Research Group, PO Box 2000, Tampere 33521, Finland.
Intensive Care Medicine, Department of Perioperative, Intensive Care and Pain Medicine, University of Helsinki, Helsinki University Hospital, PO Box 340, Helsinki 00029, Finland.
Thromb Res. 2016 Mar;139:10-6. doi: 10.1016/j.thromres.2015.12.016. Epub 2016 Jan 4.
Critical care patients are prone to venous thromboembolism (VTE) and, thus, pharmacological thromboprophylaxis is generally advised. Low-molecular weight heparins (LMWHs) have become the drug of choice in ICU patients, since their predictable and reproducible dose response. Monitoring their pharmacological effect is not usually necessary except in special occasions (i.e. with obese or renal failure patients), where anti-FXa level measuring is recommended. However, there is neither recommendation of adequate anti-FXa levels in critically ill patients nor is it known whether peak or trough level should be measured. The aim of this systematic review was to evaluate the recommended LMWH doses, and the reasons to monitor anti-FXa levels.
We searched MEDLINE, Scopus, Cochrane Central Register of Controlled Trials and ClinicalTrials.com to identify all potentially relevant studies. Prospective studies done in critically ill patients were included if at least one anti-FXa level (i.e. peak or trough) after any specified LMWH thromboprophylaxis dose was measured.
Total 18 eligible studies including 1644 patients were included. There was a wide variation in the median peak anti-FXa levels (<0.1-0.35IU/ml). Trough levels were generally low. Of note, none of the studies detected any correlation with bleeding events and anti-FXa levels. Low trough level increased incidence of DVT in one study only.
Based on the current literature, no definite conclusions can be drawn on targeted anti-FXa level in critically ill patients when using LMWH thromboprophylaxis.
重症监护患者易发生静脉血栓栓塞（VTE），因此通常建议进行药物性血栓预防。低分子量肝素（LMWHs）已成为ICU患者的首选药物，因为其剂量反应具有可预测性和可重复性。除特殊情况（如肥胖或肾衰竭患者）外，通常无需监测其药理作用，在这些特殊情况下，建议测量抗Xa因子水平。然而，对于重症患者，既没有关于适当抗Xa因子水平的建议，也不清楚应该测量峰值还是谷值水平。本系统评价的目的是评估推荐的LMWH剂量以及监测抗Xa因子水平的原因。
我们检索了MEDLINE、Scopus、Cochrane对照试验中央注册库和ClinicalTrials.com，以确定所有潜在相关研究。如果在任何指定的LMWH血栓预防剂量后测量了至少一个抗Xa因子水平（即峰值或谷值），则纳入在重症患者中进行的前瞻性研究。
共纳入18项符合条件的研究，包括1644例患者。抗Xa因子峰值水平中位数差异很大（<0.1 - 0.35IU/ml）。谷值水平通常较低。值得注意的是，没有一项研究发现出血事件与抗Xa因子水平之间存在任何相关性。仅在一项研究中，低谷值水平增加了深静脉血栓形成的发生率。
基于目前的文献，在使用LMWH进行血栓预防时，对于重症患者的目标抗Xa因子水平无法得出明确结论。
