Department of Clinical Sciences, Colorado State University, Fort Collins, Colorado.
North Carolina State University, Raleigh, North Carolina.
J Vet Intern Med. 2020 Mar;34(2):710-718. doi: 10.1111/jvim.15694. Epub 2020 Jan 25.
Dogs with protein-losing nephropathy (PLN) are treated with antiplatelet drugs for thromboprophylaxis but no standardized method exists to measure drug response. It is also unknown if clopidogrel metabolite concentrations [CM] differ between healthy and PLN dogs.
Assess response to aspirin or clopidogrel in PLN dogs using platelet aggregometry (PA) and compare [CM] between healthy and PLN dogs.
Six healthy and 14 PLN dogs.
Platelet aggregometry using adenosine diphosphate (ADP), arachidonic acid (AA), and saline was performed in healthy dogs at baseline and 1-week postclopidogrel administration to identify responders or nonresponders. A decrease of ≥60% for ADP or ≥30% for AA at 1 or 3 hours postpill was used to define a responder. At 1 and 3 hours postclopidogrel, [CM] and PA were measured in healthy and PLN dogs. Platelet aggregometry was performed in PLN dogs at baseline, 1, 6, and 12 weeks after clopidogrel or aspirin administration.
In PLN dogs receiving clopidogrel, PA differed from baseline at all time points for ADP but not for AA at any time point. Most dogs responded at 1 or both time points except for 1 dog that showed no response. For PLN dogs receiving aspirin, no differences from baseline were observed at any time point for either ADP or AA. No differences in [CM] were found at either time point between healthy and PLN dogs.
Platelet aggregometry may represent an objective method to evaluate response to clopidogrel or aspirin treatment and PLN dogs appear to metabolize clopidogrel similarly to healthy dogs.
患有蛋白丢失性肾病(PLN)的狗接受抗血小板药物进行血栓预防,但目前尚不存在测量药物反应的标准化方法。也不清楚健康狗和 PLN 狗之间的氯吡格雷代谢物浓度 [CM] 是否存在差异。
使用血小板聚集仪(PA)评估 PLN 狗对阿司匹林或氯吡格雷的反应,并比较健康狗和 PLN 狗之间的 [CM]。
6 只健康狗和 14 只 PLN 狗。
在健康狗中,在基线时和氯吡格雷给药后 1 周进行血小板聚集仪检测,使用二磷酸腺苷(ADP)、花生四烯酸(AA)和生理盐水,以确定反应者或非反应者。在服药后 1 或 3 小时,ADP 下降≥60%或 AA 下降≥30%定义为反应者。在氯吡格雷给药后 1 和 3 小时,测量健康狗和 PLN 狗的 [CM]和 PA。在 PLN 狗中,在氯吡格雷或阿司匹林给药后 1、6 和 12 周时进行基线、1 周和 6 周的血小板聚集仪检测。
在接受氯吡格雷的 PLN 狗中,除 1 只狗无反应外,在所有时间点,ADP 的 PA 均与基线不同,但在任何时间点,AA 的 PA 均与基线无差异。大多数狗在 1 个或 2 个时间点均有反应。在接受阿司匹林的 PLN 狗中,在任何时间点,ADP 或 AA 的 PA 均与基线无差异。在任何时间点,健康狗和 PLN 狗之间的 [CM] 均无差异。
血小板聚集仪可能是评估氯吡格雷或阿司匹林治疗反应的一种客观方法,PLN 狗似乎与健康狗相似地代谢氯吡格雷。