Brodin Ellen, Børvik Trond, Sandset Per Morten, Bønaa Kaare H, Nordøy Arne, Hansen John-Bjarne
Center for Atherothrombotic Research in Tromsø, Department of Medicine, Institute of Clinical Medicine, University of Tromsø, 9037 Tromsø, Norway.
Thromb Haemost. 2004 Jul;92(1):178-84. doi: 10.1160/TH03-11-0674.
Formation of an occlusive thrombus by exposure of tissue factor (TF) to circulating blood and subsequent triggering of coagulation by TF-FVIIa complexes on ruptured atherosclerotic plaques is thought to be a key event in acute MI. Tissue factor pathway inhibitor (TFPI) is a potent inhibitor of TF-induced coagulation by neutralizing FXa and inhibiting the TF-FVIIa complex. A case control study was conducted to investigate the role of coagulation activation in MI. Sixty-two patients with verified MI, 40-60 yrs of age, were recruited into the study and examined 1-4 years after the acute coronary event. Thrombin-antithrombin complex (TAT) was significantly increased in MI patients (8.2 +/- 12.9 microg/l vs. 3.9 +/- 2.6 microg/l, p=0.01). In contrast, FVIIa was lower in MI patients (41 +/- 13 mU/ml vs. 48 +/- 15 mU/ml, p=0.003) accompanied by an increase in plasma free TFPI antigen (20.9 +/- 5.0 ng/ml vs. 19.2 +/- 4.9 ng/ml, p=0.03). Significant trends for increase in triglycerides and total cholesterol across quartiles of free TFPI Ag were found in both groups, whereas HDL cholesterol decreased across quartiles of TFPI among control subjects. The compensatory increase in plasma free TFPI with established lipid and haemostatic risk factors were abrogated in the MI patients. An apparent increase in the basal activation of the coagulation system was observed in young patients with MI. Enhanced coagulation activation was accompanied by a decrease in FVIIa and increase in free TFPI Ag, probably reflecting a modest triggering of TF-induced coagulation in these patients.
组织因子（TF）暴露于循环血液中，随后TF - FVIIa复合物在破裂的动脉粥样硬化斑块上触发凝血，从而形成闭塞性血栓，被认为是急性心肌梗死（MI）的关键事件。组织因子途径抑制剂（TFPI）是一种通过中和FXa并抑制TF - FVIIa复合物来有效抑制TF诱导凝血的物质。进行了一项病例对照研究，以调查凝血激活在心肌梗死中的作用。62例年龄在40 - 60岁之间经证实患有心肌梗死的患者被纳入研究，并在急性冠状动脉事件发生后1 - 4年进行检查。心肌梗死患者的凝血酶 - 抗凝血酶复合物（TAT）显著升高（8.2±12.9微克/升对3.9±2.6微克/升，p = 0.01）。相比之下，心肌梗死患者的FVIIa较低（41±13毫国际单位/毫升对48±15毫国际单位/毫升，p = 0.003），同时血浆游离TFPI抗原增加（20.9±5.0纳克/毫升对19.2±4.9纳克/毫升，p = 0.03）。在两组中，游离TFPI抗原四分位数范围内甘油三酯和总胆固醇均有显著升高趋势，而对照组中TFPI四分位数范围内高密度脂蛋白胆固醇降低。在心肌梗死患者中，血浆游离TFPI与既定的脂质和止血危险因素的代偿性增加被消除。在年轻的心肌梗死患者中观察到凝血系统基础激活明显增加。凝血激活增强伴随着FVIIa降低和游离TFPI抗原增加，这可能反映了这些患者中TF诱导凝血的适度触发。
