Tan Kiat T, Tayebjee Muzahir H, Lynd Cheryl, Blann Andrew D, Lip Gregory Y H
Haemostasis, Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham B18 7QH, UK.
Ann Med. 2005;37(1):61-6. doi: 10.1080/07853890410018943.
There is increased platelet activation in many cardiovascular diseases. This observation may explain the presence of increased levels of platelet microparticles (PMP) in these diseases. However, whether or not levels of PMPs inter-relate with other markers of platelet activation, such as soluble P-selectin, or with disease severity, is unknown. We therefore hypothesized raised PMP levels in stable peripheral artery disease (PAD) intermittent claudication (IC), with an additional increase in severe PAD critical limb ischaemia (CLI). Furthermore, we tested the hypothesis that PMP levels are correlated with other markers of platelet activation, such as soluble P-selectin, membrane bound P-selectin (CD62P) and 63.
Patients with PAD were recruited from the vascular outpatient and inpatient facilities at a teaching hospital. Age- and sex-matched controls were also recruited from healthy volunteers. Venous blood was obtained from 23 patients with severe disease (CLI), 36 with moderate disease (IC), and from 30 healthy controls. The percentage of platelets positive for CD62P and CD63, as well as the numbers of PMPs were defined by flow cytometry. Plasma soluble P selectin was measured by enzyme-linked immunosorbent assay (ELISA).
PMPs were increased relative to healthy controls in patients with IC, with a further increase in CLI (P<0.001). Soluble P selectin and CD62+ve platelets were raised in both patient groups, but there was no difference amongst the two patient groups. CD63+ve cells were raised only in CLI compared to healthy controls. In multivariate analysis, only PMP and soluble P selectin independently predicted disease severity, and the two markers correlated modestly (r=0.345, P<0.001).
Increased PMP and soluble P selectin are both related to the severity of symptomatic PAD. However, it is uncertain if this relationship is a cause or effect of atherosclerosis. This finding may have clinical implications as PMPs have the potential to influence the progression of atheroma as well as promote thrombosis.
在许多心血管疾病中血小板活化增加。这一观察结果可能解释了这些疾病中血小板微粒（PMP）水平升高的原因。然而，PMP水平是否与血小板活化的其他标志物（如可溶性P选择素）或疾病严重程度相关尚不清楚。因此，我们假设稳定型外周动脉疾病（PAD）间歇性跛行（IC）患者的PMP水平升高，而严重PAD临界肢体缺血（CLI）患者的PMP水平会进一步升高。此外，我们检验了PMP水平与血小板活化的其他标志物（如可溶性P选择素、膜结合P选择素（CD62P）和63）相关的假设。
从一家教学医院的血管门诊和住院部招募PAD患者。还从健康志愿者中招募年龄和性别匹配的对照组。从23例重症患者（CLI）、36例中度患者（IC）和30例健康对照者中采集静脉血。通过流式细胞术确定CD62P和CD63阳性血小板的百分比以及PMP的数量。采用酶联免疫吸附测定（ELISA）法检测血浆可溶性P选择素。
与健康对照组相比，IC患者的PMP增加，CLI患者的PMP进一步增加（P<0.001）。两个患者组的可溶性P选择素和CD62+阳性血小板均升高，但两个患者组之间无差异。与健康对照组相比，仅CLI患者的CD63+阳性细胞升高。在多变量分析中，只有PMP和可溶性P选择素能独立预测疾病严重程度，且这两种标志物之间存在适度相关性（r=0.345，P<0.001）。
PMP和可溶性P选择素增加均与有症状PAD的严重程度相关。然而，这种关系是动脉粥样硬化的原因还是结果尚不确定。这一发现可能具有临床意义，因为PMP有可能影响动脉粥样硬化的进展以及促进血栓形成。
