Dirkmann Daniel, Görlinger Klaus, Peters Jürgen
From the Klinik für Anästhesiologie und Intensivmedizin, Universität Duisburg-Essen, Universitätsklinikum Essen, Essen, Germany.
Anesth Analg. 2014 Sep;119(3):533-542. doi: 10.1213/ANE.0000000000000333.
Although thromboelastometry (ROTEM®) and thrombelastography can be used for bedside diagnosis of fibrinolysis, the time needed for detection is often prolonged. Since untreated fibrinolysis can result in consumption of coagulation factors and bleeding, early diagnosis and decision making are desirable. Accordingly, we assessed ROTEM variables from extrinsically activated assays with (APTEM) and without (EXTEM) addition of aprotinin for their ability to rapidly identify fibrinolysis. Specifically, we tested the hypotheses that prolonged clotting time, clot formation time, low clot firmness (at 5, 10, 15, and 20 minutes, designated A5, A10, A15, and A20, respectively), low maximum clot firmness (MCF) in EXTEM assays, and differences in these variables from parallel APTEM and EXTEM assays (designated as Δvariables) predict fibrinolysis.
Data from 411 thromboelastometric measurements (obtained from 352 patients) with fibrinolysis and from 2537 measurements without fibrinolysis (obtained from 1605 patients) were assessed and analyzed using receiver operating characteristics. Data were analyzed as a pooled fibrinolysis cohort, and subanalyses were performed from sets assigned to categories of fibrinolysis related to the timing of thrombus lysis (i.e., a decrease of clot firmness to <15% of MCF within 30, 45, and 60 minutes, respectively). A lower 95% confidence limit of the area under the receiver operating characteristic curve (AUC [SE] <0.6) was considered a failure to substantially improve detection of increased fibrinolysis. AUCs were compared to identify the variable providing the best predictive association with fibrinolysis. As a secondary end point, optimum cutoff values at the point estimate corresponding to the greatest Youden index were calculated along with the respective sensitivities and specificities.
In the pooled cohort, clot formation time (AUC: 0.652 [0.016]), α-angle (AUC: 0.675 [0.015]), A5 (AUC: 0.718 [0.013]), A10 (AUC: 0.734 [0.0.13]), A15 (AUC: 0.752 [0.013]), A20 (AUC: 0.771 [0.013]), and MCF (AUC: 0.799 [0.012]) predicted fibrinolysis. Fibrinolysis was also predicted by ΔA15 (AUC: 0.675 [0.016]), ΔA20 (AUC: 0.719 [0.015]), and ΔMCF (AUC: 0.812 [0.013]). AUCs increased in a time-related fashion. The ability to predict subsequent fibrinolysis based on thromboelastometry was higher when it occurred early rather than later during testing. However, for prediction of late fibrinolysis, only MCF (AUC: 0.655 [0.025]) appears to be potentially clinically useful.
Low early values of clot firmness in extrinsically activated thromboelastometric assays are associated with fibrinolysis and improve its early detection. Additional assays with aprotinin fail to improve the early diagnosis of fibrinolysis compared with assays without aprotinin.
尽管血栓弹力图（ROTEM®）和血栓弹力描记法可用于床边纤溶诊断，但检测所需时间往往较长。由于未治疗的纤溶会导致凝血因子消耗和出血，因此早期诊断和决策很有必要。因此，我们评估了外源性激活试验中添加抑肽酶（APTEM）和未添加抑肽酶（EXTEM）时的血栓弹力图变量，以确定其快速识别纤溶的能力。具体而言，我们检验了以下假设：EXTEM试验中凝血时间延长、凝块形成时间延长、凝块硬度低（分别在5、10、15和20分钟时，记为A5、A10、A15和A20）、最大凝块硬度（MCF）低，以及平行APTEM和EXTEM试验中这些变量的差异（记为Δ变量）可预测纤溶。
对411次纤溶血栓弹力图测量数据（来自352例患者）和2537次无纤溶测量数据（来自1605例患者）进行评估，并使用受试者工作特征曲线进行分析。数据作为合并的纤溶队列进行分析，并根据血栓溶解时间（即分别在30、45和60分钟内凝块硬度降至MCF的<15%）对纤溶相关类别进行亚组分析。受试者工作特征曲线下面积的较低95%置信限（AUC[SE]<0.6）被认为未能显著改善对纤溶增加的检测。比较AUC以确定与纤溶具有最佳预测关联的变量。作为次要终点，计算对应于最大约登指数的点估计值处的最佳截断值以及相应敏感度和特异度。
在合并队列中，凝块形成时间（AUC：0.652[0.016]）、α角（AUC：0.675[0.015]）、A5（AUC：0.718[0.013]）、A10（AUC：0.734[0.013]）、A15（AUC：0.752[0.013]）、A20（AUC：0.771[0.013]）和MCF（AUC：0.799[0.012]）可预测纤溶。ΔA15（AUC：0.675[0.016]）、ΔA20（AUC：0.719[0.015]）和ΔMCF（AUC：0.812[0.013]）也可预测纤溶。AUC以时间相关方式增加。基于血栓弹力图预测后续纤溶的能力在检测早期发生时高于后期。然而，对于晚期纤溶的预测，只有MCF（AUC：0.655[0.025]）似乎可能具有临床实用性。
外源性激活血栓弹力图试验中早期凝块硬度低值与纤溶相关，并可改善其早期检测。与未添加抑肽酶的试验相比，添加抑肽酶的额外试验未能改善纤溶的早期诊断。
