Sharpe Kristopher S, Center Sharon A, Randolph John F, Brooks Marjory B, Warner Karen L, Stokol Tracy, Barr Stephen C, Felippe M Julia
Department of Clinical Sciences, Cornell University, Ithaca, NY 14853, USA.
Am J Vet Res. 2010 Nov;71(11):1294-304. doi: 10.2460/ajvr.71.11.1294.
To evaluate the influence of treatment with ultralow-dose aspirin (ULDAsp) on platelet aggregation, P-selectin (CD62P) expression, and formation of platelet-leukocyte aggregates in clinically normal dogs.
18 clinically normal dogs.
Studies were conducted before and 24 hours after ULDAsp administration (0.5 mg/kg, PO, q 24 h, for 2 days). Whole blood impedance aggregometry for the assessment of platelet function was performed with sodium citrate-anticoagulated blood and aggregation agonists (ADP at 20, 10, and 5 μmol/L; collagen at 10, 5, and 2 μg/mL). Onset, maximum response, and rate of platelet aggregation were recorded. Flow cytometric assays were configured to detect thrombin-induced CD62P expression and platelet-leukocyte aggregates in EDTA-anticoagulated whole blood. Externalized platelet CD62P and constitutive CD61 (GPIIIa) were labeled with antibodies conjugated to phycoerythrin (PE) and fluorescein isothiocyanate (FITC), respectively. Red blood cell-lysed paraformaldehyde-fixed EDTA-anticoagulated whole blood was dual labeled with CD61-FITC and a panleukocyte antibody (CD18-PE) to characterize platelet-leukocyte aggregates.
ULDAsp significantly delayed platelet aggregation onset with ADP at 20 μmol/L by 54% to 104%, attenuated maximum aggregation with various concentrations of ADP and collagen by ≥ 41%, and slowed aggregation rate with the highest ADP and collagen concentrations by ≥ 39%. Depending on the parameter tested, up to 30% of dogs failed to have an ULDAsp effect. Thrombin stimulation significantly increased CD62P expression in platelets and platelet-leukocyte aggregates, but ULDAsp did not alter basal or thrombin-stimulated CD62P expression.
ULDAsp treatment of clinically normal dogs impaired platelet aggregation in most dogs, but did not influence CD62P platelet membrane expression.
评估超低剂量阿司匹林（ULDAsp）治疗对临床正常犬血小板聚集、P-选择素（CD62P）表达及血小板-白细胞聚集体形成的影响。
18只临床正常犬。
在给予ULDAsp（0.5mg/kg，口服，每24小时1次，共2天）前及给药后24小时进行研究。采用柠檬酸钠抗凝血液和聚集激动剂（20、10和5μmol/L的ADP；10、5和2μg/mL的胶原）进行全血阻抗聚集测定以评估血小板功能。记录血小板聚集的起始时间、最大反应和聚集速率。流式细胞术检测配置用于检测凝血酶诱导的EDTA抗凝全血中CD62P表达及血小板-白细胞聚集体。血小板表面CD62P和组成性CD61（糖蛋白IIIa）分别用与藻红蛋白（PE）和异硫氰酸荧光素（FITC）偶联的抗体标记。红细胞裂解的多聚甲醛固定的EDTA抗凝全血用CD61-FITC和全白细胞抗体（CD18-PE）进行双重标记以鉴定血小板-白细胞聚集体。
ULDAsp使20μmol/L ADP诱导的血小板聚集起始时间显著延迟54%至104%，使不同浓度ADP和胶原诱导的最大聚集率降低≥41%，使最高浓度ADP和胶原诱导的聚集速率减慢≥39%。根据所测试的参数，高达30%的犬未出现ULDAsp效应。凝血酶刺激显著增加血小板及血小板-白细胞聚集体中CD62P表达，但ULDAsp未改变基础或凝血酶刺激后的CD62P表达。
ULDAsp治疗临床正常犬使大多数犬的血小板聚集受损，但不影响血小板膜CD62P表达。
