Swallow R A, Agarwala R A, Dawkins K D, Curzen N P
Wessex Cardiac Unit, Southampton University Hospital, Southampton, UK.
Platelets. 2006 Sep;17(6):385-92. doi: 10.1080/09537100600757521.
Modified thrombelastography (TEG) is a simple point of care test that provides an overall assessment of ex vivo clot formation and currently has limited clinical application. We evaluated the ability of TEG to assess the effects of antiplatelet therapy on clot formation using a novel assessment parameter (the area under curve). Forty healthy volunteers were divided into four groups of 10. Group A took aspirin 75 mg once daily for 7 days followed by aspirin 75 mg and clopidogrel 75 mg once daily in combination for 7 more days. Blood samples were taken for analysis at day 0 and days 7 and 14. Group B took a single 300 mg dose of aspirin. Group C took 600 mg of clopidogrel only. Group D took 300 mg of aspirin and 600 mg of clopidogrel at the same time. For groups B, C and D blood was taken prior to drug administration and at 2, 6 and 24 h afterwards. Each sample was tested by TEG in four channels following activation using (1) kaolin, (2) activator F (Act F), a direct activator of fibrin, (3) Act F + arachidonic acid (AA) and (4) Act F + adenosine diphosphate (ADP). Parameters measured included the maximum amplitude (MA) of the clot and the area under the TEG-generated curve at 1 h. Significant, time-dependent reductions in MA and area were seen in the AA-activated samples following administration of aspirin in all groups as compared to baseline. By contrast, there were no significant differences in MA or area in the AA-activated samples with clopidogrel alone. Significant reductions were also seen in MA and area in ADP-activated samples from volunteers treated with clopidogrel as compared to baseline. Three out of 10 subjects receiving 600 mg clopidogrel had a reduction in their responses of 30% or less, thus identifying them as relatively resistant to the drug. This study identifies a rapid, reliable method for assessing the time-dependent effects of antiplatelet therapy on clotting using a novel parameter of area of the TEG trace, which could have an important clinical application as a point of care test of efficacy, particularly in the context of acute coronary syndromes and percutaneous coronary intervention.
改良血栓弹力图(TEG)是一种简单的床旁检测方法,可对体外凝血形成进行全面评估,目前临床应用有限。我们使用一种新的评估参数(曲线下面积)评估了TEG评估抗血小板治疗对凝血形成影响的能力。40名健康志愿者被分为四组,每组10人。A组每天服用75毫克阿司匹林,共7天,之后每天联合服用75毫克阿司匹林和75毫克氯吡格雷,再服用7天。在第0天、第7天和第14天采集血样进行分析。B组单次服用300毫克阿司匹林。C组仅服用600毫克氯吡格雷。D组同时服用300毫克阿司匹林和600毫克氯吡格雷。对于B、C和D组,在给药前以及给药后2小时、6小时和24小时采集血液。每个样本在使用(1)高岭土、(2)激活剂F(Act F,一种纤维蛋白直接激活剂)、(3)Act F + 花生四烯酸(AA)和(4)Act F + 二磷酸腺苷(ADP)激活后,通过TEG在四个通道进行检测。测量的参数包括血凝块的最大振幅(MA)和TEG生成曲线在1小时时的曲线下面积。与基线相比,所有组在服用阿司匹林后,AA激活样本中的MA和面积均出现显著的、随时间的降低。相比之下,单独使用氯吡格雷的AA激活样本中的MA或面积没有显著差异。与基线相比,接受氯吡格雷治疗的志愿者的ADP激活样本中的MA和面积也出现显著降低。10名接受600毫克氯吡格雷治疗的受试者中有3人的反应降低了30%或更少,因此将他们确定为对该药物相对耐药。本研究确定了一种快速、可靠的方法,使用TEG曲线面积这一新参数评估抗血小板治疗对凝血的时间依赖性影响,作为疗效的床旁检测,这在急性冠状动脉综合征和经皮冠状动脉介入治疗的背景下可能具有重要的临床应用价值。