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Whole Blood Point-of-Care Testing for Incomplete Reversal With Idarucizumab in Supratherapeutic Dabigatran.

超治疗达比加群用Idarucizumab进行不完全逆转的全血即时检测。

  • 影响因子:2.27
  • DOI:10.1213/ANE.0000000000004419
  • 作者列表:"Takeshita S","Tanaka KA","Sawa T","Sanda M","Mizobe T","Ogawa S
  • 发表时间:2020-02-01
Abstract

BACKGROUND:Incomplete reversal with a recommended 5-g dose of idarucizumab has been reported in patients with excessively high dabigatran concentrations. A timely detection of reversal failure after idarucizumab using whole blood (WB) coagulation testing is clinically useful. The aims of this study were to determine residual dabigatran activity after idarucizumab on thrombin generation (TG) using in vitro supratherapeutic dabigatran models and to compare 4 WB point-of-care tests (activated partial thromboplastin time [aPTT], prothrombin time [PT], and 2 thromboelastometry tests) with the TG results. METHODS:Blood samples from 12 healthy volunteers were spiked in vitro with 0-5000 ng/mL of dabigatran. Dabigatran reversal was evaluated by adding 1000 μg/mL of idarucizumab (Praxbind) to dabigatran-spiked samples, which reflect the administration of 5-g idarucizumab to a 70-kg patient. Residual dabigatran activity was assessed using the calibrated automated TG (Thrombinoscope) in platelet-poor plasma samples. The TG results were compared with WB aPTT (DRIHEMATO APTT-S) and PT (DRIHEMATO PT-S) using CG02N analyzer, thromboelastometry (ROTEM) triggered by ellagic acid (INTEM) and tissue factor (EXTEM). RESULTS:At a therapeutic concentration of dabigatran (200 ng/mL), the lag time was prolonged, and peak TG was decreased. The effects of dabigatran on TG were increased up to 1000 ng/mL, and TG was obliterated at higher supratherapeutic dabigatran levels (P < .001 versus control, respectively). TG was fully restored with idarucizumab when dabigatran was ≤2000 ng/mL, but residual anticoagulant activity was observed at higher dabigatran levels. Dabigatran prolonged WB aPTT and PT concentration dependently, and residual prolongations were observed when idarucizumab was added to 3000 or 5000 ng/mL of dabigatran (P < .001 versus control, respectively). In contrast, both INTEM and EXTEM clotting times were reversed toward reference ranges at all dabigatran concentrations when idarucizumab was added. CONCLUSIONS:Our data indicate that the recommended dose of idarucizumab may not restore TG completely with excessively elevated concentrations of dabigatran. All WB measurements with aPTT, PT, and thromboelastometry predicted supratherapeutic dabigatran concentrations, whereas those tests varied in sensitivity to residual anticoagulant activity after reversal. WB aPTT corresponded well with plasma TG changes among those measurements, but the use of thromboelastometry may overestimate the effect of idarucizumab. Caution should be exercised before extrapolating in vitro point-of-care data to the clinical monitoring of dabigatran reversal.

摘要

背景: 在达比加群浓度过高的患者中报道了推荐剂量 5g的idarucizumab的不完全逆转。使用全血 (WB) 凝血试验及时检测idarucizumab后的逆转失败在临床上是有用的。本研究的目的是确定idarucizumab对凝血酶生成 (TG) 后残留的达比加群活性使用体外超治疗达比加群模型,比较 4 种WB床旁试验 (活化部分凝血活酶时间 [aPTT] 、凝血酶原时间 [PT] 和 2 种血栓弹力图试验) 与TG结果。 方法: 对 12 名健康志愿者的血液样本进行体外加标,加入 0-5000 ng/mL的达比加群。通过向达比加群加标样品中加入 1000 μ g/mL的idarucizumab (Praxbind) 来评价达比加群逆转,这反映了对 70 kg患者给予 5-g idarucizumab。在血小板贫乏的血浆样本中,使用校准的自动TG (凝血酶镜) 评估残余达比加群活性。TG结果与WB aPTT (DRIHEMATO APTT-S) 和PT (DRIHEMATO PT-S) 进行比较,使用CG02N分析仪,由鞣花酸 (INTEM) 触发的血栓弹力图 (ROTEM) 和组织因子 (EXTEM)。 结果: 达比加群在治疗浓度 (200 ng/mL) 下,滞后时间延长,TG峰值降低。达比加群对TG的影响增加至 1000 ng/mL,并且在较高的超治疗达比加群水平下,TG被消除 (分别与对照组相比,P <.001)。当达比加群 ≤ 2000 ng/mL时,idarucizumab完全恢复TG,但在较高的达比加群水平下观察到残余抗凝活性。达比加群依赖性延长WB aPTT和PT浓度,当加入idarucizumab至 3000 或 5000 ng/mL达比加群时观察到残余延长 (分别与对照组比较P <.001)。相比之下,当加入idarucizumab时,INTEM和EXTEM凝血时间均逆转至所有达比加群浓度的参考范围。 结论: 我们的数据表明,随着达比加群浓度的过度升高,idarucizumab的推荐剂量可能无法完全恢复TG。所有使用aPTT、PT和血栓弹力图的WB测量均预测了超治疗达比加群浓度,而这些测试对逆转后残余抗凝活性的敏感性不同。在这些测量中,WB aPTT与血浆TG变化很好地对应,但使用血栓弹力图可能高估了idarucizumab的作用。在将体外即时数据外推至达比加群逆转的临床监测之前应谨慎。

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影响因子:2.86
发表时间:2020-01-01
DOI:10.1097/TA.0000000000002498
作者列表:["Williams J","Merutka N","Meyer D","Bai Y","Prater S","Cabrera R","Holcomb JB","Wade CE","Love JD","Cotton BA"]

METHODS:PURPOSE:Following US military implementation of a cold-stored whole blood program, several US trauma centers have begun incorporating uncrossmatched, group O cold-stored whole blood into civilian trauma resuscitation. We set out to evaluate the safety profile, transfusion reactions events, and impact of low-titer group O whole blood (LTO-WB) at our center. METHODS:In November 2017, we added LTO-WB to each of our helicopters and to our emergency department (ED) refrigerator, alongside that of existing red blood cells and plasma. We collected information on all patients with trauma receiving prehospital or ED transfusion of uncrossed, emergency release blood products between November 2017 and June 2018. Patients were divided into those receiving any LTO-WB and those receiving only red blood cell and or plasma (COMP). Serial hemolysis panels were obtained at 3 hours, 24 hours, and 48 hours. All data were run using STATA 12.1. Statistical significance was set at p < 0.05. RESULTS:One hundred ninety-eight patients received LTO-WB and 152 patients received COMP. There were no differences in age, sex, or mechanism. The LTO-WB patients had higher chest Abbreviated Injury Scale scores (median, 3 vs. 2; p = 0.027), as well as worse arrival base excess (median, -7 vs. -5; p = 0.014) and lactate (5.1 vs. 3.5; p < 0.001). The LTO-WB patients received less post-ED blood products than the COMP patients (median, 0 vs. 3; p = 0.001). There was no difference in survival (LTO-WB, 73%; COMP, 74%; p = 0.805). There were only two suspected transfusion reactions, both in the COMP group (p = 0.061). There was no difference in hemolysis panel values. Controlling for age, severity of injury, and prehospital physiology, LTO-WB was associated with a 53% reduction in post-ED blood product transfusion (odds ratio, 0.47; 0.23-0.94 95% CI; p = 0.033) and two-fold increase in likelihood of survival (odds ratio, 2.19; 1.01-4.76 95% CI; p = 0.047). CONCLUSION:Low-titer group O whole blood has similar evidence of laboratory hemolysis, similar transfusion reaction rates, and is associated with a reduction in post-ED transfusions and increase likelihood of survival. LEVEL OF EVIDENCE:Therapeutic, Level II.

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翻译标题与摘要 下载文献
影响因子:1.33
发表时间:2020-01-01
DOI:10.3233/CH-180541
作者列表:["Chayer B","Allard L","Qin Z","Garcia-Duitama J","Roger L","Destrempes F","Cailhier JF","Denault A","Cloutier G"]

METHODS:BACKGROUND:An enhanced inflammatory response is a trigger to the production of blood macromolecules involved in abnormally high levels of erythrocyte aggregation. OBJECTIVE:This study aimed at demonstrating for the first time the clinical feasibility of a non-invasive ultrasound-based erythrocyte aggregation quantitative measurement method for potential application in critical care medicine. METHODS:Erythrocyte aggregation was evaluated using modeling of the backscatter coefficient with the Structure Factor Size and Attenuation Estimator (SFSAE). SFSAE spectral parameters W (packing factor) and D (mean aggregate diameter) were measured within the antebrachial vein of the forearm and tibial vein of the leg in 50 healthy participants at natural flow and reduced flow controlled by a pressurized bracelet. Blood samples were also collected to measure erythrocyte aggregation ex vivo with an erythroaggregometer (parameter S10). RESULTS:W and Din vivo measurements were positively correlated with the ex vivoS10 index for both measurement sites and shear rates (correlations between 0.35-0.81, p < 0.05). Measurement at low shear rate was found to increase the sensitivity and reliability of this non-invasive measurement method. CONCLUSIONS:We behold that the SFSAE method presents systemic measures of the erythrocyte aggregation level, since results on upper and lower limbs were highly correlated.

翻译标题与摘要 下载文献
影响因子:2.27
发表时间:2020-02-01
DOI:10.1213/ANE.0000000000004419
作者列表:["Takeshita S","Tanaka KA","Sawa T","Sanda M","Mizobe T","Ogawa S"]

METHODS:BACKGROUND:Incomplete reversal with a recommended 5-g dose of idarucizumab has been reported in patients with excessively high dabigatran concentrations. A timely detection of reversal failure after idarucizumab using whole blood (WB) coagulation testing is clinically useful. The aims of this study were to determine residual dabigatran activity after idarucizumab on thrombin generation (TG) using in vitro supratherapeutic dabigatran models and to compare 4 WB point-of-care tests (activated partial thromboplastin time [aPTT], prothrombin time [PT], and 2 thromboelastometry tests) with the TG results. METHODS:Blood samples from 12 healthy volunteers were spiked in vitro with 0-5000 ng/mL of dabigatran. Dabigatran reversal was evaluated by adding 1000 μg/mL of idarucizumab (Praxbind) to dabigatran-spiked samples, which reflect the administration of 5-g idarucizumab to a 70-kg patient. Residual dabigatran activity was assessed using the calibrated automated TG (Thrombinoscope) in platelet-poor plasma samples. The TG results were compared with WB aPTT (DRIHEMATO APTT-S) and PT (DRIHEMATO PT-S) using CG02N analyzer, thromboelastometry (ROTEM) triggered by ellagic acid (INTEM) and tissue factor (EXTEM). RESULTS:At a therapeutic concentration of dabigatran (200 ng/mL), the lag time was prolonged, and peak TG was decreased. The effects of dabigatran on TG were increased up to 1000 ng/mL, and TG was obliterated at higher supratherapeutic dabigatran levels (P < .001 versus control, respectively). TG was fully restored with idarucizumab when dabigatran was ≤2000 ng/mL, but residual anticoagulant activity was observed at higher dabigatran levels. Dabigatran prolonged WB aPTT and PT concentration dependently, and residual prolongations were observed when idarucizumab was added to 3000 or 5000 ng/mL of dabigatran (P < .001 versus control, respectively). In contrast, both INTEM and EXTEM clotting times were reversed toward reference ranges at all dabigatran concentrations when idarucizumab was added. CONCLUSIONS:Our data indicate that the recommended dose of idarucizumab may not restore TG completely with excessively elevated concentrations of dabigatran. All WB measurements with aPTT, PT, and thromboelastometry predicted supratherapeutic dabigatran concentrations, whereas those tests varied in sensitivity to residual anticoagulant activity after reversal. WB aPTT corresponded well with plasma TG changes among those measurements, but the use of thromboelastometry may overestimate the effect of idarucizumab. Caution should be exercised before extrapolating in vitro point-of-care data to the clinical monitoring of dabigatran reversal.

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血液检测可分为血液一般检测、溶血性贫血的实验室检测、骨髓细胞学检测、血型鉴定与交叉配血试验。可以检测出常见血液病的血液学持征。

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