Honda Yuko, Morishima Yoshiyuki
Biological Research Laboratories, R & D Division, Daiichi Sankyo Co., Ltd, Tokyo, Japan.
Biological Research Laboratories, R & D Division, Daiichi Sankyo Co., Ltd, Tokyo, Japan.
Thromb Res. 2015 May;135(5):958-62. doi: 10.1016/j.thromres.2015.03.001. Epub 2015 Mar 9.
Patients with atrial fibrillation undergoing percutaneous coronary intervention may require combination therapy with anticoagulants and antiplatelet agents. The objectives of this study were to establish an assay which can evaluate the effects of both anticoagulants and P2Y12 receptor antagonists and determine the effects of edoxaban, a direct factor Xa inhibitor, and P2Y12 receptor antagonists (clopidogrel and ticagrelor) alone and when combined.
Human platelet-rich plasma (PRP) from healthy subjects was stimulated with adenosine diphosphate (ADP) plus tissue factor. Thrombin generation was measured by means of calibrated automated thrombography.
Combination of 10μM ADP and low concentration (0.25 pM) tissue factor induced reproducible thrombin generation in human PRP. Edoxaban (40 and 80ng/mL), active metabolite of clopidogrel (AM-clopidogrel, 10 and 20μg/mL), and ticagrelor (3μg/mL) alone inhibited ADP plus tissue factor-induced thrombin generation. Edoxaban suppressed all 5 parameters (lag time, peak, time to peak, endogenous thrombin potential, and maximum rate), whereas AM-clopidogrel and ticagrelor inhibited 4 and 3 parameters, respectively. Concomitant treatment with edoxaban and AM-clopidogrel or ticagrelor produced an additive inhibition of thrombin generation compared to the single treatments.
The thrombin generation assay induced by ADP plus tissue factor can detect the activities of both edoxaban and P2Y12 receptor antagonists. Combination of edoxaban and a P2Y12 receptor antagonist shows additive inhibition. These results suggest that ADP plus tissue factor-induced thrombin generation may be a useful measurement to assess the combination effects of anticoagulants and P2Y12 receptor antagonists in a single assay.
接受经皮冠状动脉介入治疗的房颤患者可能需要联合使用抗凝剂和抗血小板药物。本研究的目的是建立一种能够评估抗凝剂和P2Y12受体拮抗剂效果的检测方法，并确定直接Xa因子抑制剂依度沙班以及单独使用和联合使用时P2Y12受体拮抗剂（氯吡格雷和替格瑞洛）的效果。
用二磷酸腺苷（ADP）加组织因子刺激健康受试者的富含血小板血浆（PRP）。通过校准自动血栓形成描记法测量凝血酶生成。
10μM ADP与低浓度（0.25 pM）组织因子联合可诱导人PRP中产生可重复的凝血酶生成。依度沙班（40和80 ng/mL）、氯吡格雷的活性代谢产物（AM-氯吡格雷，10和20μg/mL）以及替格瑞洛（3μg/mL）单独使用时均可抑制ADP加组织因子诱导的凝血酶生成。依度沙班可抑制所有5个参数（延迟时间、峰值、达到峰值的时间、内源性凝血酶潜力和最大速率），而AM-氯吡格雷和替格瑞洛分别抑制4个和3个参数。与单一治疗相比，依度沙班与AM-氯吡格雷或替格瑞洛联合治疗对凝血酶生成具有相加抑制作用。
ADP加组织因子诱导的凝血酶生成检测可检测依度沙班和P2Y12受体拮抗剂的活性。依度沙班与P2Y12受体拮抗剂联合显示出相加抑制作用。这些结果表明，ADP加组织因子诱导的凝血酶生成可能是一种在单一检测中评估抗凝剂和P2Y12受体拮抗剂联合效果的有用测量方法。
