通过传统实验室参数和旋转血栓弹力图监测危重症患者的阿加曲班和比伐芦定抗凝治疗——一项前瞻性对照随机双盲临床试验
Monitoring of argatroban and lepirudin anticoagulation in critically ill patients by conventional laboratory parameters and rotational thromboelastometry - a prospectively controlled randomized double-blind clinical trial.
作者信息
Beiderlinden Martin, Werner Patrick, Bahlmann Astrid, Kemper Johann, Brezina Tobias, Schäfer Maximilian, Görlinger Klaus, Seidel Holger, Kienbaum Peter, Treschan Tanja A
机构信息
Klinik für Anästhesiologie, Marienhospital Osnabrück, Bischofsstr. 1, 49076, Osnabrück, Germany.
Klinik für Anästhesiologie, Universitätsklinik Düsseldorf, Heinrich-Heine-Universität Düsseldorf, Moorenstr. 5, 40225, Düsseldorf, Germany.
出版信息
BMC Anesthesiol. 2018 Feb 9;18(1):18. doi: 10.1186/s12871-018-0475-y.
BACKGROUND
Argatroban or lepirudin anticoagulation therapy in patients with heparin induced thrombocytopenia (HIT) or HIT suspect is typically monitored using the activated partial thromboplastin time (aPTT). Although aPTT correlates well with plasma levels of argatroban and lepirudin in healthy volunteers, it might not be the method of choice in critically ill patients. However, in-vivo data is lacking for this patient population. Therefore, we studied in vivo whether ROTEM or global clotting times would provide an alternative for monitoring the anticoagulant intensity effects in critically ill patients.
METHODS
This study was part of the double-blind randomized trial "Argatroban versus Lepirudin in critically ill patients (ALicia)", which compared critically ill patients treated with argatroban or lepirudin. Following institutional review board approval and written informed consent, for this sub-study blood of 35 critically ill patients was analysed. Before as well as 12, 24, 48 and 72 h after initiation of argatroban or lepirudin infusion, blood was analysed for aPTT, aPTT ratios, thrombin time (TT), INTEM CT,INTEM CT ratios, EXTEM CT, EXTEM CT ratios and maximum clot firmness (MCF) and correlated with the corresponding plasma concentrations of the direct thrombin inhibitor.
RESULTS
To reach a target aPTT of 1.5 to 2 times baseline, median [IQR] plasma concentrations of 0.35 [0.01-1.2] μg/ml argatroban and 0.17 [0.1-0.32] μg/ml lepirudin were required. For both drugs, there was no significant correlation between aPTT and aPTT ratios and plasma concentrations. INTEM CT, INTEM CT ratios, EXTEM CT, EXTEM CT ratios, TT and TT ratios correlated significantly with plasma concentrations of both drugs. Additionally, agreement between argatroban plasma levels and EXTEM CT and EXTEM CT ratios were superior to agreement between argatroban plasma levels and aPTT in the Bland Altman analysis. MCF remained unchanged during therapy with both drugs.
CONCLUSION
In critically ill patients, TT and ROTEM parameters may provide better correlation to argatroban and lepirudin plasma concentrations than aPTT.
TRIAL REGISTRATION
ClinicalTrials.gov , NCT00798525 , registered on 25 Nov 2008.
背景
对于肝素诱导的血小板减少症（HIT）患者或疑似HIT患者，阿加曲班或比伐卢定抗凝治疗通常采用活化部分凝血活酶时间（aPTT）进行监测。虽然在健康志愿者中，aPTT与阿加曲班和比伐卢定的血浆水平相关性良好，但在危重症患者中它可能并非首选方法。然而，这一患者群体缺乏体内数据。因此，我们进行了一项体内研究，以确定旋转血栓弹力图（ROTEM）或全血凝固时间是否能为监测危重症患者的抗凝强度效果提供一种替代方法。
方法
本研究是双盲随机试验“危重症患者中阿加曲班与比伐卢定的比较（ALicia）”的一部分，该试验比较了接受阿加曲班或比伐卢定治疗的危重症患者。经机构审查委员会批准并获得书面知情同意后，对本亚研究中35例危重症患者的血液进行了分析。在开始输注阿加曲班或比伐卢定之前以及之后12、24、48和72小时，对血液进行aPTT、aPTT比值、凝血酶时间（TT）、INTEM CT、INTEM CT比值、EXTEM CT、EXTEM CT比值和最大血凝块硬度（MCF）分析，并与直接凝血酶抑制剂的相应血浆浓度进行相关性分析。
结果
为使aPTT达到基线的1.5至2倍，所需阿加曲班和比伐卢定的血浆浓度中位数[四分位间距]分别为0.35[0.01 - 1.2]μg/ml和0.17[0.1 - 0.32]μg/ml。对于这两种药物，aPTT和aPTT比值与血浆浓度之间均无显著相关性。INTEM CT、INTEM CT比值、EXTEM CT、EXTEM CT比值、TT和TT比值与两种药物的血浆浓度均显著相关。此外，在布兰德 -阿尔特曼分析中，阿加曲班血浆水平与EXTEM CT及EXTEM CT比值之间的一致性优于阿加曲班血浆水平与aPTT之间的一致性。在两种药物治疗期间，MCF均保持不变。
结论
在危重症患者中，与aPTT相比，TT和ROTEM参数可能与阿加曲班和比伐卢定的血浆浓度具有更好的相关性。
试验注册
ClinicalTrials.gov，NCT00798525，于2008年11月25日注册。
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