Brooks Marjory B, Divers Thomas J, Watts Ashlee E, Ness Sally L, Frye Amelia H, Stokol Tracy, Fubini Susan L
Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14850, USA.
Am J Vet Res. 2013 Sep;74(9):1212-22. doi: 10.2460/ajvr.74.9.1212.
To evaluate the platelet activation response before and after treatment with clopidogrel in horses.
12 healthy adult mares.
In a masked study, horses (6/group) were randomly allocated to alternately receive placebo or clopidogrel via nasogastric tube at a loading dose of 4 mg/kg followed by 2 mg/kg every 24 hours. Blood samples were collected before and 72 hours after initiation of treatment for ADP- and collagen-induced light transmission aggregometry; determination of closure time in collagen-ADP cartridges; modified thrombelastography for comparison of maximal amplitudes generated by kaolin, reptilase, and reptilase plus ADP activation; and flow cytometric tests to detect platelet fibrinogen binding, P-selectin expression, and phosphatidylserine externalization before and after ex vivo stimulation with thrombin, convulxin, thrombin with convulxin, and calcium ionophore.
Clopidogrel administration induced a significant decrease in mean aggregation response to 5 μM and 10 μM ADP stimulation; however, 2 horses had resistance to clopidogrel's inhibitory action. Significant differences after clopidogrel treatment were not found in any other tests of platelet function.
Assays using commercially available reagents were configured to measure different variables of the platelet activation response; however, clopidogrel's platelet inhibitory action was only detected by ADP-induced light transmission aggregometry. Results also suggested that horses, like humans, have interindividual variability in response to clopidogrel that may influence the drug's clinical efficacy as an antiplatelet agent.
评估马匹使用氯吡格雷治疗前后的血小板活化反应。
12匹健康成年母马。
在一项盲法研究中，将马匹（每组6匹）随机分配，通过鼻胃管交替给予安慰剂或氯吡格雷，负荷剂量为4mg/kg，随后每24小时给予2mg/kg。在治疗开始前和开始治疗72小时后采集血样，用于ADP和胶原诱导的透光率聚集试验；测定胶原-ADP检测盒中的封闭时间；采用改良血栓弹力图比较高岭土、蛇毒凝血酶和蛇毒凝血酶加ADP激活产生的最大振幅；以及进行流式细胞术检测，以检测在体外用凝血酶、convulxin、凝血酶与convulxin以及钙离子载体刺激前后的血小板纤维蛋白原结合、P-选择素表达和磷脂酰丝氨酸外化情况。
给予氯吡格雷后，对5μM和10μM ADP刺激的平均聚集反应显著降低；然而，有2匹马对氯吡格雷的抑制作用产生抵抗。在其他血小板功能检测中，氯吡格雷治疗后未发现显著差异。
使用市售试剂的检测方法用于测量血小板活化反应的不同变量；然而，氯吡格雷的血小板抑制作用仅通过ADP诱导的透光率聚集试验检测到。结果还表明，马匹与人类一样，对氯吡格雷的反应存在个体差异，这可能会影响该药物作为抗血小板药物的临床疗效。
