Wessex Cardiothoracic Unit, Southampton University Hospital, UK.
Platelets. 2009 Sep;20(6):386-90. doi: 10.1080/09537100903003227.
The most widely accepted methods of assessing response to clopidogrel involve isolated ADP-induced platelet aggregation. Whilst poor response determined by these assays correlates with adverse clinical events, the number of "poor responders" is far higher than the number of events attributed to treatment failure. Clopidogrel may have effects that cannot be assessed using isolated ADP-induced aggregation. We have investigated the effect of clopidogrel on Arachidonic Acid (AA) induced platelet activation-an "aspirin specific" pathway using a novel near patient assay. Thirty four volunteers on no medication and 36 patients, on maintenance therapy with aspirin 75 mg daily, were recruited. Blood tests for Thrombelastogram PlateletMapping were taken immediately prior to and 6 hours after administration of a 600 mg clopidogrel loading dose. Changes in the area under the response curve at 15 minutes (AUC15) with both ADP- and AA-stimulation were calculated as were the corresponding percentage platelet and percentage clotting inhibition (%PIn and %CIn). There were predictable and significant changes in the AUC15 of the ADP channel in response to clopidogrel and the corresponding %PIn and %CIn in both volunteers and patients. There were also significant reductions in the AUC15 of the AA channel (presented as Mean +/- 95%CI), by 27.2 +/- 11.8%, p = 0.005 in volunteers and 35.0 +/- 8.2%, p < 0.001 in patients) and increases in the %PIn and %CIn calculated using the AA channel in volunteers (by 20.0 +/- 11.4%, p + 0.02 and 32.3 +/- 12.8%, p < 0.001 respectively) and patients (by 24.2 +/- 8.6%, p < 0.001 and by 18.0 +/- 8.6, p < 0.001 respectively). Clopidogrel has both independent and aspirin-synergistic effects on AA-induced platelet activation suggesting potentiation of the antiplatelet activity of aspirin. This effect may be clinically important and is not detected by current "gold standard" methods of assessing response to clopidogrel.
最广泛接受的评估氯吡格雷反应的方法涉及孤立的 ADP 诱导的血小板聚集。虽然这些测定的不良反应与不良临床事件相关，但“不良反应者”的数量远远超过归因于治疗失败的事件数量。氯吡格雷可能具有无法通过孤立的 ADP 诱导聚集来评估的作用。我们使用新型即时患者检测方法，研究了氯吡格雷对花生四烯酸（AA）诱导的血小板激活（“阿司匹林特异性”途径）的影响。招募了 34 名未服用药物的志愿者和 36 名每日服用阿司匹林 75 毫克维持治疗的患者。在给予 600 毫克氯吡格雷负荷剂量之前和之后立即进行血栓弹性图血小板图谱血液检查。计算 ADP 和 AA 刺激时 15 分钟时的反应曲线下面积（AUC15）的变化，以及相应的血小板和凝血抑制百分比（%PIn 和 %CIn）。志愿者和患者中，氯吡格雷对 ADP 通道的 AUC15 以及相应的%PIn 和%CIn 均有可预测且显著的变化。AA 通道的 AUC15 也显著降低（以平均值 +/- 95%CI 表示），志愿者中降低 27.2 +/- 11.8%，p = 0.005，患者中降低 35.0 +/- 8.2%，p < 0.001），并且志愿者中使用 AA 通道计算的 %PIn 和 %CIn 增加（增加 20.0 +/- 11.4%，p + 0.02 和增加 32.3 +/- 12.8%，p < 0.001），患者中增加 24.2 +/- 8.6%，p < 0.001 和增加 18.0 +/- 8.6%，p < 0.001）。氯吡格雷对 AA 诱导的血小板激活具有独立的和与阿司匹林协同的作用，提示增强了阿司匹林的抗血小板作用。这种作用可能具有临床重要性，并且无法通过当前评估氯吡格雷反应的“金标准”方法检测到。
