Falciani M, Gori A M, Fedi S, Chiarugi L, Simonetti I, Dabizzi R P, Prisco D, Pepe G, Abbate R, Gensini G F, Neri Serneri G G
Istituto di Clinica Medica Generale e Cardiologia, University of Florence, Italy.
Thromb Haemost. 1998 Mar;79(3):495-9.
Several studies have shown that thrombosis and inflammation play an important role in the pathogenesis of Ischaemic Heart Disease (IHD). In particular, Tissue Factor (TF) is responsible for the thrombogenicity of the atherosclerotic plaque and plays a key role in triggering thrombin generation. The aim of this study was to evaluate the TF/Tissue Factor Pathway Inhibitor (TFPI) system in patients with IHD. We have studied 55 patients with IHD and not on heparin [18 with unstable angina (UA), 24 with effort angina (EA) and 13 with previous myocardial infarction (MI)] and 48 sex- and age-matched healthy volunteers, by measuring plasma levels of TF, TFPI, Prothrombin Fragment 1-2 (F1+2), and Thrombin Antithrombin Complexes (TAT). TF plasma levels in IHD patients (median 215.4 pg/ml; range 72.6 to 834.3 pg/ml) were significantly (p<0.001) higher than those found in control subjects (median 142.5 pg/ml; range 28.0-255.3 pg/ml). Similarly, TFPI plasma levels in IHD patients were significantly higher (median 129.0 ng/ml; range 30.3-316.8 ng/ml; p<0.001) than those found in control subjects (median 60.4 ng/ml; range 20.8-151.3 ng/ml). UA patients showed higher amounts of TF and TFPI plasma levels (TF median 255.6 pg/ml; range 148.8-834.3 pg/ml; TFPI median 137.7 ng/ml; range 38.3-316.8 ng/ml) than patients with EA (TF median 182.0 pg/ml; range 72.6-380.0 pg/ml; TFPI median 115.2 ng/ml; range 47.0-196.8 ng/ml) and MI (TF median 213.9 pg/ml; range 125.0 to 341.9 pg/ml; TFPI median 130.5 ng/ml; range 94.0-207.8 ng/ml). Similar levels of TF and TFPI were found in patients with mono- or bivasal coronary lesions. A positive correlation was observed between TF and TFPI plasma levels (r = 0.57, p<0.001). Excess thrombin formation in patients with IHD was documented by TAT (median 5.2 microg/l; range 1.7-21.0 microg/l) and F1+2 levels (median 1.4 nmol/l; range 0.6 to 6.2 nmol/l) both significantly higher (p<0.001) than those found in control subjects (TAT median 2.3 microg/l; range 1.4-4.2 microg/l; F1+2 median 0.7 nmol/l; range 0.3-1.3 nmol/l). As in other conditions associated with cell-mediated clotting activation (cancer and DIC), also in IHD high levels of circulating TF are present. Endothelial cells and monocytes are the possible common source of TF and TFPI. The blood clotting activation observed in these patients may be related to elevated TF circulating levels not sufficiently inhibited by the elevated TFPI plasma levels present.
多项研究表明，血栓形成和炎症在缺血性心脏病（IHD）的发病机制中起重要作用。特别是，组织因子（TF）导致动脉粥样硬化斑块的血栓形成性，并在触发凝血酶生成中起关键作用。本研究的目的是评估IHD患者的TF/组织因子途径抑制剂（TFPI）系统。我们研究了55例未使用肝素的IHD患者[18例不稳定型心绞痛（UA）患者、24例劳力性心绞痛（EA）患者和13例既往心肌梗死（MI）患者]以及48例年龄和性别匹配的健康志愿者，通过测量血浆中TF、TFPI、凝血酶原片段1-2（F1+2）和凝血酶-抗凝血酶复合物（TAT）的水平。IHD患者的TF血浆水平（中位数215.4 pg/ml；范围72.6至834.3 pg/ml）显著高于对照组（中位数142.5 pg/ml；范围28.0-255.3 pg/ml）（p<0.001）。同样，IHD患者的TFPI血浆水平也显著高于对照组（中位数129.0 ng/ml；范围30.3-316.8 ng/ml；p<0.001）（中位数60.4 ng/ml；范围20.8-151.3 ng/ml）。UA患者的TF和TFPI血浆水平（TF中位数255.6 pg/ml；范围148.8-834.3 pg/ml；TFPI中位数137.7 ng/ml；范围38.3-316.8 ng/ml）高于EA患者（TF中位数182.0 pg/ml；范围72.6-380.0 pg/ml；TFPI中位数115.2 ng/ml；范围47.0-196.8 ng/ml）和MI患者（TF中位数213.9 pg/ml；范围125.0至341.9 pg/ml；TFPI中位数130.5 ng/ml；范围94.0-207.8 ng/ml）。单支或双支冠状动脉病变患者的TF和TFPI水平相似。TF和TFPI血浆水平之间存在正相关（r = 0.57，p<0.001）。TAT（中位数5.2 μg/l；范围1.7-21.0 μg/l）和F1+2水平（中位数1.4 nmol/l；范围0.6至6.2 nmol/l）均显著高于对照组（p<0.001），证明IHD患者存在过量的凝血酶形成（TAT中位数2.3 μg/l；范围1.4-4.2 μg/l；F1+2中位数0.7 nmol/l；范围0.3-1.3 nmol/l）。与其他与细胞介导的凝血激活相关的情况（癌症和弥散性血管内凝血）一样，IHD患者也存在高水平的循环TF。内皮细胞和单核细胞可能是TF和TFPI的共同来源。在这些患者中观察到的凝血激活可能与循环TF水平升高有关，而升高的TFPI血浆水平未能充分抑制这种升高。
