The effect of 17β-oestradiol on variables of coagulation and fibrinolysis in postmenopausal women with type 2 diabetes mellitus
The effect of 17β-oestradiol on variables of coagulation and fibrinolysis in postmenopausal women with type 2 diabetes mellitus
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DOI：
10.1016/s1537-1891(02)00303-8
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发表时间：
2002-08-01
影响因子：
4
通讯作者：
Kluft, C
中科院分区：
文献类型：
--
作者：
Brussard, HE;Leuven, JAG;Kluft, C
2型糖尿病经常伴有高凝状态和纤溶功能低下。两者都与心血管风险增加有关，但也可能与内皮损伤有关。对非糖尿病患者的研究表明，无对抗性雌激素替代疗法（oERT）可降低心血管风险，这可能部分通过对凝血和纤溶的影响来介导。在一项双盲、随机、安慰剂对照试验中，我们评估了6周内每天口服17 β-雌二醇对绝经后2型糖尿病妇女凝血和纤溶指标的影响，我们观察到oERT后凝血因子VII（FVII）和血管性血友病因子（vWF）显著升高，而已经很高的纤维蛋白原没有变化。oERT后凝血酶原片段1+2（F1+2）增加，而凝血酶-抗凝血酶（达特）复合物无变化，但F1+2和达特的增量相关。可溶性纤维蛋白（SF）水平保持稳定。在纤溶方面，观察到纤溶酶原激活物抑制物1（派-1）明显降低，但组织型纤溶酶原激活物抗原（t-PA-Ag）或活性无显著变化，尽管纤溶活性评估为t-PA活性（t-PA-Act）在oERT后有增加的趋势。然而，纤溶活性指标（纤溶酶-抗纤溶酶复合物和纤维蛋白降解产物）并没有改变。oERT增加C-反应蛋白（CRP），但没有凝血或纤溶变化显着相关的CRP changes.It的结论是，oERT增加凝血效力以及纤溶效力提出的问题，在其平衡的净效应。F1+2的增加表明，在糖尿病女性中，oERT有效地增加了凝血的慢性、持续激活，根据SF的不变水平判断，这似乎在血室中得到了补偿或无效。血管壁中疑似纤维蛋白形成增加至少不会导致纤维蛋白原降解产物（TDP）增加，这表明可能存在蓄积和心血管风险增加。结果表明，在研究其他类别的妇女和添加孕酮的影响时，应特别注意纤维蛋白周转。(C)2002年爱思唯尔科技有限公司All rights reserved.
Type 2 diabetes mellitus is frequently accompanied by hypercoagulability and hypofibrinolysis. Both are related to increased cardiovascular risk, but possibly with endothelial injury as well. Studies with nondiabetic persons indicate that unopposed oestrogen replacement therapy (oERT) decreases cardiovascular risk, possibly mediated in part by effects on coagulation and fibrinolysis. In a double-blind, randomised placebo-controlled trial, we assessed the effect of oral 17beta-oestradiol daily during 6 weeks on indicators of coagulation and of fibrinolysis in postmenopausal women with type 2 diabetes mellitus.We observed significant increases of Factor VII (FVII) and von Willebrand factor (vWF) after oERT and no change in the already high fibrinogen. Prothrombin fragment 1+2 (F1+2) increased after oERT, whereas thrombin-antithrombin (TAT) complexes was unchanged, but increments of F1+2 and TAT correlated. Soluble fibrin (SF) levels remained stable.In fibrinolysis, a clear reduction in plasminogen activator inhibitor 1 (PAI-1) was observed, but no significant change in tissue-type plasminogen activator antigen (t-PA-Ag) or activity was found, although fibrinolytic activity assessed as t-PA activity (t-PA-Act) tended to increase after oERT. Indicators of fibrinolytic activity (plasmin-antiplasmin complexes and fibrin degradation products) however did not change.oERT increased C-reactive protein (CRP) but none of the coagulation or fibrinolysis changes significantly associated with the CRP changes.It is concluded that oERT increases the coagulation potency as well as the fibrinolytic potency raising the question of the net effect in their balance. Increase in F1+2 suggests that in diabetic women oERT effectively increases the chronic, continuous activation of coagulation, which appears to be compensated for or not effective in the blood compartment as judged from the unchanged levels of SF. Suspected increased fibrin formation in the vascular wall is at least not followed by increases in fibrinogen degradation products (TDP), which suggests the possibility of accumulation and increased cardiovascular risk. The results indicate that specific attention should be paid to fibrin turnover in studying other categories of women and the effects of the addition of progesterone. (C) 2002 Elsevier Science Inc. All rights reserved.