Institute of Cardiology, Jagiellonian University Medical College, 80 Prądnicka Str. 31-202, Kraków, Poland.
Center for Research and Medical Technology, John Paul II Hospital, Pradnicka 80, 31-202, Kraków, Poland.
Med Oncol. 2019 Mar 19;36(4):37. doi: 10.1007/s12032-019-1262-4.
Dense fibrin networks resistant to lysis have been reported in patients at high risk of thromboembolism. Little is known about fibrin clot properties in cancer. We investigated fibrin clot properties and their determinants in patients with inoperable lung cancer.
We enrolled 150 patients with advanced lung cancer prior to therapy and 90 control subjects matched by age, sex, cardiovascular disease, and diabetes. Plasma clot permeability (K), turbidimetric analysis of clot formation, clot lysis time (CLT), microparticle-associated tissue factor (MP-TF) activity, thrombin generation, and serum cotinine levels were determined.
Lung cancer patients, compared with controls, formed at a faster rate (- 8.1% lag phase) denser plasma fibrin networks (- 27.2% K) that displayed impaired lysis (+ 26.5% CLT), along with 19.5% higher MP-TF activity and 100% higher peak thrombin generated, also after adjustment for potential confounders. Cotinine levels were associated with fibrin maximum absorbance (r = 0.20, p = 0.016) and K (r = - 0.50, p < 0.0001) in cancer patients. On multivariate regression analysis, an increase in cotinine levels was a predictor of low K (the lower quartile, < 5.8 × 10 cm; odds ratio = 1.21 per 10 ng/ml, 95% confidence interval 1.02-1.46), but not CLT.
Advanced lung cancer is associated with the prothrombotic plasma clot phenotype largely driven by smoking.
有报道称，高血栓栓塞风险患者的纤维蛋白网络致密且不易溶解。关于癌症患者纤维蛋白凝块特性的了解甚少。我们研究了无法手术的肺癌患者的纤维蛋白凝块特性及其决定因素。
我们在治疗前招募了 150 名晚期肺癌患者和 90 名年龄、性别、心血管疾病和糖尿病相匹配的对照组。测定了血浆凝块通透性（K）、凝块形成的比浊分析、凝块溶解时间（CLT）、微粒相关组织因子（MP-TF）活性、凝血酶生成和血清可替宁水平。
与对照组相比，肺癌患者的纤维蛋白网络更快形成（-8.1%的滞后期），并且纤维蛋白网络更致密（-27.2%的 K），溶解受损（CLT 增加 26.5%），同时 MP-TF 活性增加 19.5%，生成的最大凝血酶增加 100%，即使在调整了潜在混杂因素后也是如此。可替宁水平与癌症患者的纤维蛋白最大吸光度（r=0.20，p=0.016）和 K（r=-0.50，p<0.0001）呈正相关。多元回归分析显示，可替宁水平升高是 K 值降低（较低四分位数，<5.8×10 cm；比值比=每 10 ng/ml 增加 1.21，95%置信区间为 1.02-1.46）的预测因子，但不是 CLT。
晚期肺癌与血栓形成前的血浆凝块表型相关，主要由吸烟引起。
