Hypercoagulability in chronic kidney disease is associated with coagulation activation but not endothelial function
Hypercoagulability in chronic kidney disease is associated with coagulation activation but not endothelial function
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DOI：
10.1016/j.thromres.2008.03.024
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发表时间：
2008-01-01
影响因子：
7.5
通讯作者：
Dogra, G. K.
中科院分区：
文献类型：
--
作者：
Adams, M. J.;Irish, A. B.;Dogra, G. K.
简介：慢性肾脏病患者表现出高凝状态的特征，并具有内皮功能障碍，这可能导致其心血管风险增加。我们研究了慢性肾脏病患者凝血激活和血管功能之间的关系。材料和方法：我们测量了凝血组织因子途径的参数（组织因子、因子VIIc和因子X）;天然抑制剂（组织因子途径抑制物、蛋白C、游离和总蛋白S、抗凝血酶III）和凝血激活标志物（凝血酶-抗凝血酶复合物，凝血酶原片段1 + 2）在66例4期和5期慢性肾脏病患者和36例健康对照中的变化。它们与血管功能标志物的关系（流动介导的扩张，可溶性E-选择素和血栓调节蛋白）和炎症介质结果：组织因子途径表达上调（组织因子和因子VIIc增加），凝血酶原片段1 + 2增加，抗凝血酶III和游离蛋白S：与健康对照相比，在患者中发现总蛋白S。组织因子抗原升高与肌酐和白细胞介素6显著独立相关（P < 0.001）。在慢性肾脏病中，凝血因子X和抗凝血酶III均降低，且相关（r = 0.58; P < 0.001）。凝血和抗凝的变化是独立的内皮functions.Conclusions的所有措施：凝血和消耗或减少一些天然抗凝剂在慢性肾脏疾病的TF途径的显着激活与肾功能不全的程度，但不相关的血管功能异常。这些数据与慢性肾脏疾病的高凝状态一致，这种高凝状态可能独立于基于内皮的调节，但与炎症状态相关。(C)2008爱思唯尔有限公司保留所有权利。
Introduction: Patients with chronic kidney disease exhibit features of a hypercoagutable state and have endothetial dysfunction, which may contribute to their increased cardiovascular risk. We examined the relationship between coagulation activation and vascular function in patients with chronic kidney disease.Materials and Methods: We measured parameters of the tissue factor pathway of blood coagulation (tissue factor, factor VIIc and factor X); natural inhibitors (tissue factor pathway inhibitor, protein C, free and total protein S, antithrombin III) and markers of coagulation activation (thrombin-antithrombin complexes, prothrombin fragment 1 + 2) in 66 stage 4&5 chronic kidney disease patients and 36 healthy controls. Their relationship with markers of vascular function (flow mediated dilatation, soluble E-selectin and thrombomodulin) and a mediator of inflammation (interteukin-6) was determined.Results: Up-regulation of the tissue factor pathway (increased tissue factor and factor VIIc), increased prothrombin fragment 1 + 2 and significant reductions in antithrombin III and the ratio of free protein S: total protein S were found in patients compared to healthy controls. Increased tissue factor antigen was significantly and independently correlated with creatinine and interleukin-6 (P < 0.001). Factor X and antithrombin III were both reduced in chronic kidney disease and correlated (r = 0.58; P < 0.001). Changes in coagulation and anti-coagulation were independent of all measures of endothelial function.Conclusions: Significant activation of the TF pathway of coagulation and depletion or reduction of some natural anticoagutants in chronic kidney disease was correlated with the degree of renal dysfunction, but not correlated with the abnormalities of vascular function. These data are consistent with a hypercoagulable state in chronic kidney disease that may be independent of endothetial based regulation but associated with an inflammatory state. (C) 2008 Elsevier Ltd. All rights reserved.