Abstract：
Direct thrombin inhibitors, including argatroban, are increasingly used for anticoagulation during venovenous extracorporeal membrane oxygenation (VV ECMO). In many centers activated partial thromboplastin time (aPTT) is used for monitoring, but it can be affected by several confounders. The aim of this study was to evaluate the safety and efficacy of anticoagulation with argatroban titrated according to diluted thrombin time targets (hemoclot™ assay) compared to anti-Xa guided anticoagulation with unfractionated heparin (UFH).
METHODS: This cohort study included adults at two tertiary care centers who required VV ECMO for severe COVID-19-related acute respiratory distress syndrome (CARDS). Patients received center-dependent argatroban or UFH for anticoagulation during ECMO. Argatroban was guided following a hemoclot™ target range of 0.4-0.6 μg/ml. UFH was guided by anti-factor Xa (antiXa) levels (0.2-0.3 IU/ml). The primary outcome was safety of argatroban compared to UFH, assessed by time to first clinically relevant bleeding event or death during ECMO. Secondary outcomes included efficacy (time to thromboembolism) and feasibility (proportion of anticoagulation targets within range).
RESULTS: From 2019 to 2021 57 patients were included in the study with 27 patients (47 %) receiving argatroban and 30 patients (53 %) receiving UFH. The time to the first clinically relevant bleeding or death during ECMO was similar between groups (HR (argatroban vs. UFH): 1.012, 95 % CI 0.44-2.35, p = 0.978). Argatroban was associated with a decreased risk for thromboembolism compared to UFH (HR 0.494 (95 % CI 0.26-0.95; p = 0.034)). The overall proportion of anticoagulation within target ranges was not different between groups (46 % (23-54 %) vs. 46 % (37 %-57 %), p = 0.45).
CONCLUSIONS: Anticoagulation with argatroban according to hemoclot™ targets (0.4-0.6 μg/ml) compared to antiXa guided UFH (0.2-0.3 IU/ml) is safe and may prolong thromboembolism-free time in patients with severe ARDS requiring VV ECMO.
METHODS: This cohort study included adults at two tertiary care centers who required VV ECMO for severe COVID-19-related acute respiratory distress syndrome (CARDS). Patients received center-dependent argatroban or UFH for anticoagulation during ECMO. Argatroban was guided following a hemoclot™ target range of 0.4-0.6 μg/ml. UFH was guided by anti-factor Xa (antiXa) levels (0.2-0.3 IU/ml). The primary outcome was safety of argatroban compared to UFH, assessed by time to first clinically relevant bleeding event or death during ECMO. Secondary outcomes included efficacy (time to thromboembolism) and feasibility (proportion of anticoagulation targets within range).
RESULTS: From 2019 to 2021 57 patients were included in the study with 27 patients (47 %) receiving argatroban and 30 patients (53 %) receiving UFH. The time to the first clinically relevant bleeding or death during ECMO was similar between groups (HR (argatroban vs. UFH): 1.012, 95 % CI 0.44-2.35, p = 0.978). Argatroban was associated with a decreased risk for thromboembolism compared to UFH (HR 0.494 (95 % CI 0.26-0.95; p = 0.034)). The overall proportion of anticoagulation within target ranges was not different between groups (46 % (23-54 %) vs. 46 % (37 %-57 %), p = 0.45).
CONCLUSIONS: Anticoagulation with argatroban according to hemoclot™ targets (0.4-0.6 μg/ml) compared to antiXa guided UFH (0.2-0.3 IU/ml) is safe and may prolong thromboembolism-free time in patients with severe ARDS requiring VV ECMO.
摘要：
直接凝血酶抑制剂,包括阿加曲班,越来越多地用于静脉体外膜氧合（VVECMO）期间的抗凝治疗。在许多中心，活化部分凝血活酶时间（aPTT）用于监测，但它可能会受到几个混杂因素的影响。这项研究的目的是评估根据稀释的凝血酶时间目标（hemoclot™测定）滴定的阿加曲班抗凝的安全性和有效性，与使用普通肝素（UFH）的抗Xa指导抗凝相比。
方法：这项队列研究包括两个三级护理中心的成年人，他们需要VVECMO治疗严重的COVID-19相关急性呼吸窘迫综合征（CARDS）。患者在ECMO期间接受中心依赖性阿加曲班或UFH抗凝治疗。遵循0.4-0.6μg/ml的hemoclot™目标范围指导阿加曲班。UFH以抗因子Xa（antiXa）水平（0.2-0.3IU/ml）为指导。主要结果是与UFH相比，阿加曲班的安全性，根据ECMO期间首次发生临床相关出血事件或死亡的时间进行评估.次要结果包括疗效（血栓栓塞时间）和可行性（范围内的抗凝目标比例）。
结果：从2019年到2021年，57名患者被纳入研究，其中27名患者（47％）接受阿加曲班，30名患者（53％）接受UFH。两组之间在ECMO期间首次临床相关出血或死亡的时间相似(HR(argatrobanvs.UFH）：1.012，95%CI0.44-2.35，p=0.978）。与UFH相比，阿加曲班与血栓栓塞风险降低相关（HR0.494（95％CI0.26-0.95；p=0.034））。目标范围内的抗凝治疗的总体比例在组间没有差异（46％（23-54％）与46%（37%-57%），p=0.45)。
结论：根据hemoclot™目标（0.4-0.6μg/ml）使用阿加曲班进行抗凝治疗与antiXa指导的UFH（0.2-0.3IU/ml）相比是安全的，并且可能会延长需要VVECMO的严重ARDS患者的无血栓栓塞时间。
方法：这项队列研究包括两个三级护理中心的成年人，他们需要VVECMO治疗严重的COVID-19相关急性呼吸窘迫综合征（CARDS）。患者在ECMO期间接受中心依赖性阿加曲班或UFH抗凝治疗。遵循0.4-0.6μg/ml的hemoclot™目标范围指导阿加曲班。UFH以抗因子Xa（antiXa）水平（0.2-0.3IU/ml）为指导。主要结果是与UFH相比，阿加曲班的安全性，根据ECMO期间首次发生临床相关出血事件或死亡的时间进行评估.次要结果包括疗效（血栓栓塞时间）和可行性（范围内的抗凝目标比例）。
结果：从2019年到2021年，57名患者被纳入研究，其中27名患者（47％）接受阿加曲班，30名患者（53％）接受UFH。两组之间在ECMO期间首次临床相关出血或死亡的时间相似(HR(argatrobanvs.UFH）：1.012，95%CI0.44-2.35，p=0.978）。与UFH相比，阿加曲班与血栓栓塞风险降低相关（HR0.494（95％CI0.26-0.95；p=0.034））。目标范围内的抗凝治疗的总体比例在组间没有差异（46％（23-54％）与46%（37%-57%），p=0.45)。
结论：根据hemoclot™目标（0.4-0.6μg/ml）使用阿加曲班进行抗凝治疗与antiXa指导的UFH（0.2-0.3IU/ml）相比是安全的，并且可能会延长需要VVECMO的严重ARDS患者的无血栓栓塞时间。
