Absolute activated protein C concentration in acute ischemic stroke

急性和慢性缺血性卒中通常会出现血小板激活和高凝状态。凝血酶与血管内皮细胞中的血栓调节蛋白结合，激活蛋白C，激活蛋白C。APC通过抑制凝血辅因子Va和VIIIa的活性而发挥抗凝血剂的作用。APC的浓度用百分比变化值或抗原值表示，而不是绝对值。对47例急性缺血性卒中患者进行了APC检测，其中动脉粥样硬化性脑梗塞(ATI)21例(平均年龄73岁)，腔隙性脑梗塞(LI)15例(平均年龄70岁)，心源性血栓(CE)11例(平均年龄80岁)。采用酶捕捉试验(ECA)(帝人)测定APC浓度。将抗蛋白C单抗固定在微板上，封闭表面。包含AP…的示例更多的C和APC的可逆抑制剂苯甲双胺被孵育在孔中以捕获APC抗原。通过大量洗涤除去未结合的样品组分和苯甲酰胺。用发色底物测定了捕获的APC的氨解活性。分别于超急性期(发病后24小时内)、急性期(4-7天)、亚急性期(8-14天)和慢性期(30天)进行检测。发病24小时内APC绝对浓度ATI组为3.3±0.9，LI组为2.5±0.8，CE组为3.1±1.1。APC浓度在ATI和LI之间有显著差异(P<0.01)，当将患者分为穿支动脉梗塞和皮质梗塞时，两者之间的APC浓度无明显差异。至于APC浓度的时间变化，CE和ATI有随时间逐渐下降的趋势，而LI没有。我们检查了凝血和纤溶指标与APC浓度的关系，发现凝血酶原片段1+2与CE的APC浓度显著相关(p&lt；0.05)。在疾病严重程度方面，APC浓度与NIH卒中评分之间无相关性。我们首次测定了急性缺血性卒中患者APC的绝对浓度。急性期CE和ATI患者APC浓度升高。APC与凝血酶原片段1+2的相关性提示APC可作为急性卒中高凝状态的标志物之一。然而，还需要进一步的研究来提高测量的准确性和评估最合适的测量时间，特别是在急性期。补充应用APC可能为今后治疗急性缺血性中风提供一种新的治疗方法。较少

Activation of platelets and a hypercoagulable state generally occur in acute and chronic ischemic stroke. Protein C is activated to activated protein C (APC) by thrombin, which combines with thrombomodulin in endothelial cells. APC functions as an anticoagulant by inhibiting the activity of coagulation cofactors Va and VIIIa. The concentration of APC has been expressed as the % change or antigen values, not absolute values. The purpose of the present study was to determine the absolute values of the APC concentration and to assess their importance in acute ischemic stroke.We examined APC in 47 acute ischemic stroke patients, which included 21 with atherothrombotic infarction (ATI) (mean age 73), 15 with lacunar infarction (LI) (mean age 70) and 11 with cardiogenic embolism (CE) (mean age 80). The APC concentration was estimated by enzyme capture assay (ECA) (Teijin). Anti-Protein C monoclomal antibodies were immobilized in microplates, and the surface was blocked. Samples containing AP … More C and benzamidine, a reversible inhibitor of APC, were incubated in the wells for capture of APC antigen. Unbound sample constituents and the benzamidine were removed by extensive washing. The amidolytic activity of the captured APC was measured using a chromogenic substrate. The measurements were performed at the hyperacute (within 24 hours after onset), acute (4-7 days), subacute (8-14 days) and chronic (30 days) stages in each patient. Coagulant and fibrinolytic markers were determined simultaneously at each stage.The absolute APC concentration within 24 hours after onset was 3.3±0.9 in ATI, 2.5±0.8 in LI and 3,1±1.1 in CE. A significant difference was observed between ATI and LI (p<0.01), When the cases were divided into perforating artery infarction and cortical infarction, no significant difference in APC concentration was evident between them. As regards chronological changes of APC concentration, it tended to decline gradually with time in CE and ATI, but not in LI. We examined the relationship between coagulant and fibrinolytic markers and the APC concentration, and found a significant correlation between prothrombin fragment 1+2 and the APC concentration in CE (p<0.05). Concerning the severity of disease, no correlation existed between the APC concentration and NIH Stroke Scale scores.We determined the absolute concentration of APC in acute ischemic stroke patients for the first time. Elevation of the APC concentration was found in CE and ATI at the acute stage. The correlation between APC and prothrombin fragment 1+2 indicated that APC could represent one of the hypercoagulable markers in acute stroke. However, further research is needed to enhance the accuracy of measurement and to evaluate the most appropriate measuring time, especially at the acute stage. Supplementary administration of APC might provide a new therapy for acute ischemic stoke in the future. Less