Department of Clinical Sciences, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762-6100, USA.
J Vet Intern Med. 2012 Nov-Dec;26(6):1389-401. doi: 10.1111/j.1939-1676.2012.01025.x. Epub 2012 Oct 28.
Cyclosporine has been shown to alter platelet plasma membranes and have a hypercoagulable effect in humans, leading to thromboembolic complications.
HYPOTHESIS/OBJECTIVES: Our hypothesis was that by modulating platelet reactivity, cyclosporine increases the risk of thromboembolic complications. The objective was to determine the effects of cyclosporine on primary hemostasis in normal dogs.
Eight healthy, intact female dogs.
A repeated-measures design utilized flow cytometry to evaluate platelet expression of platelet reactivity markers (P-selectin and phosphatidylserine) and COX-1 and COX-2 during the administration of 2 cyclosporine dosages (19 mg/kg q12h [immunosuppressive dosage] and 5 mg/kg q24h [atopy dosage]). Urine 11-dehydro-thromboxane-B(2) (11-dTXB(2) ) concentration was normalized to urine creatinine concentration, and platelet function was analyzed by PFA-100.
After a week of the immunosuppressive dosage, all platelet reactivity markers showed a significant decrease in mean fluorescent intensity (MFI). After the atopy dosage, only P-selectin and COX-2 MFI demonstrated a change from baseline, decreasing by 29% (P = .013) and 31% (P = .003), respectively. Urinary 11-dTXB(2) -to-creatinine ratio significantly increased at all time points during the immunosuppressive dosage, but no significant change occurred during administration of the atopy dosage. PFA-100 closure times using collagen/ADP cartridges increased by 62% (P = .008) with the immunosuppressive dosage and decreased by 45% with the atopy dosage (P = .035). No significant changes in closure times occurred with collagen/epinephrine cartridges.
Our study suggests that, similar to what is observed in humans, cyclosporine alters the platelet plasma membrane and increases thromboxane production in dogs, especially at immunosuppressive dosages.
环孢素已被证明可改变血小板质膜，并在人类中产生高凝作用，导致血栓栓塞并发症。
假说/目的：我们的假设是，通过调节血小板反应性，环孢素会增加血栓栓塞并发症的风险。目的是确定环孢素对正常犬的初级止血的影响。
8 只健康、完整的雌性犬。
采用重复测量设计，利用流式细胞术评估血小板反应性标志物（P-选择素和磷脂酰丝氨酸）以及 COX-1 和 COX-2 的表达，在给予 2 种环孢素剂量（19mg/kg q12h[免疫抑制剂量]和 5mg/kg q24h[过敏剂量]）时进行评估。尿 11-脱氢血栓烷 B2（11-dTXB2）浓度与尿肌酐浓度进行归一化，通过 PFA-100 分析血小板功能。
免疫抑制剂量治疗 1 周后，所有血小板反应性标志物的平均荧光强度（MFI）均显著降低。过敏剂量后，只有 P-选择素和 COX-2 的 MFI 从基线开始发生变化，分别下降了 29%（P=0.013）和 31%（P=0.003）。免疫抑制剂量时所有时间点的尿 11-dTXB2-肌酐比值均显著增加，但过敏剂量时无明显变化。使用胶原/ADP 试剂盒时，PFA-100 闭合时间增加 62%（P=0.008），使用胶原/肾上腺素试剂盒时则减少 45%（P=0.035）。胶原/肾上腺素试剂盒的闭合时间无明显变化。
本研究表明，与在人类中观察到的情况类似，环孢素改变了犬的血小板质膜并增加了血栓烷的产生，尤其是在免疫抑制剂量下。
