Department of Clinical Sciences, Danderyd Hospital, Division of Cardiovascular Medicine, Karolinska Institutet, Stockholm, Sweden.
Department of Medicine, Division of Hematology, Coagulation Unit, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
Thromb Res. 2017 May;153:76-82. doi: 10.1016/j.thromres.2017.03.018. Epub 2017 Mar 18.
A rapid and reliable assessment of the dabigatran effect is desirable in dabigatran treated patients with uncontrolled bleeding or before acute surgery.
To evaluate how the viscoelastic point-of-care test Rotational thromboelastometry (ROTEM) and Total Thrombus-formation system (T-TAS), which studies thrombus formation under flowing conditions, correlate with dabigatran concentrations in patients with atrial fibrillation (AF).
ROTEM using the reagents In-tem, Ex-tem, Fib-tem or low tissue factor concentration (TF), and T-TAS with the AR-chip (shear rate 600s, representing flow in large arteries) were investigated in whole blood samples. Plasma concentrations were determined by mass spectrometry (LC-MS/MS) at trough and post-dose in 30 patients on dabigatran 150mg BID.
Median plasma dabigatran concentrations at trough were 86ng/mL (29-150) and post-dose (2.8h after ingestion) 175ng/mL (67-490). The ROTEM clotting time (CT) correlated strongly with dabigatran concentrations when activated with the reagents Ex-tem (r=0.92, p<0.01) and Fib-tem (r=0.93, p<0.01), while with In-tem and low TF the correlation was weaker (r=0.72 and r=0.36, p<0.01). There were significant but weaker correlations also between dabigatran concentrations and T-TAS variables (r-values 0.39-0.41, p<0.01), aPTT (r=0.70, p<0.01) and PT-INR (r=0.43, p<0.01) respectively.
ROTEM Ex-tem and Fib-tem CT shows a strong correlation with dabigatran concentrations in real-life AF-patients, and results are obtained within minutes. This could make ROTEM useful in acute situations. T-TAS detect differences in hemostasis caused by dabigatran, but the relationships to plasma concentrations of dabigatran are weaker than for ROTEM CT with the settings used in this study.
在接受达比加群治疗且出血未得到控制或需进行急诊手术的患者中，需要快速可靠地评估达比加群的作用。
评估旋转血栓弹性测定法（ROTEM）和全血栓形成系统（T-TAS）等即时检测血栓弹性检测法（VTE）与房颤（AF）患者达比加群浓度的相关性，这两种检测方法都可在流动条件下研究血栓形成。
用 INTEM、EXTEM、FIBTEM 或低组织因子浓度（TF）试剂检测 ROTEM，用 AR 芯片（剪切率 600s，代表大动脉中的血流）检测 T-TAS，对 30 名服用达比加群 150mg 每日两次的患者的全血样本进行检测。通过液相色谱-质谱联用（LC-MS/MS）法在患者谷浓度和给药后 2.8 小时（服药后）检测患者血浆中的达比加群浓度。
患者谷浓度中位数为 86ng/ml（29-150），给药后 2 小时（服药后 2.8 小时）浓度中位数为 175ng/ml（67-490）。EXTEM 和 FIBTEM 试剂激活的 ROTEM 凝血时间（CT）与达比加群浓度呈强相关性（r=0.92，p<0.01；r=0.93，p<0.01），而 INTEM 和低 TF 试剂的相关性较弱（r=0.72 和 r=0.36，p<0.01）。T-TAS 各变量（r 值 0.39-0.41，p<0.01）、活化部分凝血活酶时间（aPTT，r=0.70，p<0.01）和凝血酶原时间国际标准化比值（PT-INR，r=0.43，p<0.01）与达比加群浓度之间也存在显著但较弱的相关性。
在现实生活中的 AF 患者中，ROTEM EXTEM 和 FIBTEM CT 与达比加群浓度呈强相关性，结果可在几分钟内获得。这使得 ROTEM 在急性情况下有用。T-TAS 可检测达比加群引起的止血差异，但与本研究中使用的设置相比，与达比加群血浆浓度的相关性较弱。
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