Rajagopalan Sriram, Mckay Ian, Ford Isobel, Bachoo Paul, Greaves Michael, Brittenden Julie
Vascular Unit, University of Aberdeen, Foresterhill, United Kingdom.
J Vasc Surg. 2007 Sep;46(3):485-90. doi: 10.1016/j.jvs.2007.05.039.
Patients with peripheral arterial disease (PAD) have increased mortality from cardiovascular events compared with age and sex matched controls Platelets play a major role in atherosclerosis and thrombotic vascular events. Platelet reactivity is increased in patients with PAD compared with healthy controls. We aimed to determine the relationship, if any, between platelet activation and severity of disease.
One hundred eighty-two patients with intermittent claudication (IC) or subcritical limb ischemia (SLI), defined as the presence of rest pain or ulceration, had the following investigations performed: platelet P-selectin expression and bound fibrinogen by flow cytometric analysis and platelet aggregation using the rapid platelet function assay with arachidonic acid (AA) and thrombin receptor activation peptide (TRAP) as agonists. Patients with SLI compared with IC had significantly enhanced ADP stimulated P-selectin expression (median 42.45% [inter-quartile range 33.32% to 58.5%] vs 35.2% [26.07% to 46.32%], P = .002) and bound fibrinogen (73.7% [54.3% to 83.2%] vs 63.7% [43.8% to 76.5%], P = .001). TRAP stimulated aggregation was higher (207 [153 to 238] PAU vs 183[155 to 199] PAU, P = .04) but AA mediated aggregation was not significantly different. An ankle-brachial pressure index (ABPI) of less than 0.6 was associated with increased ADP stimulated P-selectin and bound fibrinogen (P < .05). ABPI correlated inversely with ADP stimulated P-selectin expression (r = -0.228, P = .003), ADP stimulated fibrinogen binding (r = -0.156, P = .043) and TRAP stimulated aggregation (r = -0.179, P = .04).
We have demonstrated for the first time that progression of severity of PAD is not only reflected by symptoms, signs, and ABPI but also by increased platelet activity as assessed by both flow cytometry and aggregation. As patients with more severe PAD have increased cardiovascular mortality, our findings suggest that new strategies for platelet inhibitory therapy are indicated in these patients.
与年龄和性别匹配的对照组相比，外周动脉疾病（PAD）患者因心血管事件导致的死亡率更高。血小板在动脉粥样硬化和血栓性血管事件中起主要作用。与健康对照组相比，PAD患者的血小板反应性增加。我们旨在确定血小板活化与疾病严重程度之间是否存在关系。
182例间歇性跛行（IC）或亚临界肢体缺血（SLI，定义为存在静息痛或溃疡）患者进行了以下检查：通过流式细胞术分析血小板P-选择素表达和结合的纤维蛋白原，并使用以花生四烯酸（AA）和凝血酶受体激活肽（TRAP）作为激动剂的快速血小板功能测定法检测血小板聚集。与IC患者相比，SLI患者的ADP刺激的P-选择素表达显著增强（中位数42.45%[四分位间距33.32%至58.5%]对35.2%[26.07%至46.32%]，P = 0.002）以及结合的纤维蛋白原（73.7%[54.3%至83.2%]对63.7%[43.8%至76.5%]，P = 0.001）。TRAP刺激的聚集更高（207[153至238]PAU对183[155至199]PAU，P = 0.04），但AA介导的聚集无显著差异。踝臂压力指数（ABPI）小于0.6与ADP刺激的P-选择素和结合的纤维蛋白原增加相关（P < 0.05）。ABPI与ADP刺激的P-选择素表达呈负相关（r = -0.228，P = 0.003）、ADP刺激的纤维蛋白原结合（r = -0.156，P = 0.043）以及TRAP刺激的聚集（r = -0.179，P = 0.04）。
我们首次证明，PAD严重程度的进展不仅通过症状、体征和ABPI反映，还通过流式细胞术和聚集评估的血小板活性增加来反映。由于更严重PAD患者的心血管死亡率增加，我们的研究结果表明这些患者需要新的血小板抑制治疗策略。
