Institute of Cardiology, Jagiellonian University Medical College, Krakow, Poland.
Thromb Res. 2011 Oct;128(4):e24-8. doi: 10.1016/j.thromres.2011.05.004. Epub 2011 May 31.
Chronic obstructive pulmonary disease (COPD) is associated with an increased risk for thromboembolic events. We investigated thrombin generation profiles in COPD patients and their dependence on plasma factor/inhibitor composition.
Factors (f) (fII, fV, fVII, fVIII, fIX, fX), antithrombin, protein C (PC) and free tissue factor pathway inhibitor (fTFPI) from 60 COPD patients (aged 64.2 ± 10.1 years; a mean forced expiratory volume in 1 second [FEV(1)], 55.6 ± 15.8% of predicted values) were compared with those for 43 controls matched for age, sex, weight and smoking. Patients receiving anticoagulation were excluded. Using each individual's plasma coagulation protein composition, tissue factor-initiated thrombin generation was assessed computationally.
COPD patients had higher fII (115 ± 16 vs 102 ± 10%, p < 0.0001), fV (114 ± 19 vs 102 ± 12%, p = 0.0002), fVII (111 ± 15 vs 102 ± 17%, p = 0.002), fVIII (170 ± 34 vs 115 ± 27%, p < 0.0001), and fIX (119 ± 21 vs 107 ± 17%, p = 0.003), and lower fTFPI (17.7 ± 3.2 vs 18.9 ± 3.2 ng/ml, p = 0.047) compared with controls, while fX, antithrombin, and PC were similar in both groups. Computational thrombin generation profiles showed that compared with controls, COPD patients had higher maximum thrombin levels (+28.3%, p < 0.0001), rates of thrombin generation (+46.1%, p < 0.0001) and total thrombin formation (+14.4%, p < 0.001), together with shorter initiation phase of thrombin generation (p < 0.0001) and the time to maximum thrombin levels (p < 0.0001). Thrombin generation profiles in COPD patients can be normalized via correction of fII, fVIII , fIX and TFPI. The severity of COPD and inflammatory markers were not associated with thrombin generation profiles.
Prothrombotic phenotype in COPD patients is largely driven by increased prothrombin, fVIII, fIX, and lower fTFPI.
慢性阻塞性肺疾病（COPD）与血栓栓塞事件的风险增加有关。我们研究了 COPD 患者的凝血酶生成谱及其对血浆因子/抑制剂组成的依赖性。
从 60 名 COPD 患者（年龄 64.2±10.1 岁；平均第一秒用力呼气量[FEV1]为预测值的 55.6±15.8%）中比较了因子（f）（fII、fV、fVII、fVIII、fIX、fX）、抗凝血酶、蛋白 C（PC）和游离组织因子途径抑制剂（fTFPI）与 43 名年龄、性别、体重和吸烟相匹配的对照组。排除接受抗凝治疗的患者。使用每个个体的血浆凝血蛋白组成，通过计算评估组织因子引发的凝血酶生成。
COPD 患者的 fII（115±16 对 102±10%，p<0.0001）、fV（114±19 对 102±12%，p=0.0002）、fVII（111±15 对 102±17%，p=0.002）、fVIII（170±34 对 115±27%，p<0.0001）和 fIX（119±21 对 107±17%，p=0.003）较高，而 fTFPI（17.7±3.2 对 18.9±3.2ng/ml，p=0.047）较低与对照组相比，而 fX、抗凝血酶和 PC 在两组中相似。计算的凝血酶生成谱显示，与对照组相比，COPD 患者的最大凝血酶水平升高（+28.3%，p<0.0001）、凝血酶生成率升高（+46.1%，p<0.0001）和总凝血酶形成增加（+14.4%，p<0.001），以及凝血酶生成的起始阶段缩短（p<0.0001）和达到最大凝血酶水平的时间缩短（p<0.0001）。通过校正 fII、fVIII、fIX 和 TFPI，可以使 COPD 患者的凝血酶生成谱正常化。COPD 的严重程度和炎症标志物与凝血酶生成谱无关。
COPD 患者的血栓形成表型主要由凝血酶原、fVIII、fIX 和 TFPI 增加引起。
