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晚期肺癌中纤维蛋白凝块特性的改变:化疗的影响。

Altered fibrin clot properties in advanced lung cancer: impact of chemotherapy.

作者信息

Królczyk Grzegorz, Ząbczyk Michał, Czyżewicz Grzegorz, Plens Krzysztof, Prior Shannon, Butenas Saulius, Undas Anetta

机构信息

Oncology Ward, John Paul II Hospital, Cracow, Poland.

Faculty of Medicine and Health Sciences, Andrzej Frycz Modrzewski Krakow University, Cracow, Poland.

出版信息

J Thorac Dis. 2018 Dec;10(12):6863-6872. doi: 10.21037/jtd.2018.11.19.

Abstract

BACKGROUND

Faster formation of dense and poorly lyzable fibrin networks have been reported in patients at risk of thromboembolism, including cancer patients. We sought to investigate whether chemotherapy affects plasma fibrin clot properties and their determinants in lung cancer patients.

METHODS

In this observational study we enrolled 83 consecutive patients with advanced inoperable lung cancer. Plasma fibrin clot permeability (K), turbidimetric analysis of clot formation, clot lysis time (CLT), microparticle-associated tissue factor (MP-TF) activity, and thrombin generation parameters were investigated at enrolment and 3-4 months after standard chemotherapy.

RESULTS

Lung cancer patients after 4 (range, 4-5) cycles of chemotherapy had 35.6% higher D-dimer, 22.1% lower MP-TF activity, and unaltered fibrinogen compared with baseline. Chemotherapy resulted also in 7.5% increased K, 8.6% prolonged lag phase, and 5.4% shortened CLT, while thrombin generation was unchanged. Chemotherapy-related differences in clot structure were confirmed by scanning electron microscopy images. Fibrin clot properties after chemotherapy did not differ among histological types of lung cancer, cancer stages or chemotherapy regimens. Interestingly, never smoking (n=13, 16%) was associated with looser post-treatment fibrin structure as reflected by 12.3% higher K. Multiple linear regression showed that more advanced cancer stage, higher peak thrombin generation, and higher white blood cell count determined post-treatment change in K, while active smoking was associated with change in CLT.

CONCLUSIONS

Three-month chemotherapy in lung cancer patients improves clot properties despite unaffected thrombin generation, suggesting that anticancer treatment might quickly produce antithrombotic actions.

摘要

背景

据报道,包括癌症患者在内的有血栓栓塞风险的患者会更快形成致密且难以溶解的纤维蛋白网络。我们试图研究化疗是否会影响肺癌患者的血浆纤维蛋白凝块特性及其决定因素。

方法

在这项观察性研究中,我们连续纳入了83例无法手术的晚期肺癌患者。在入组时和标准化疗3 - 4个月后,对血浆纤维蛋白凝块通透性(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)活性和凝血酶生成参数进行了研究。

结果

肺癌患者在接受4(范围为4 - 5)个周期化疗后,与基线相比,D - 二聚体升高35.6%,MP - TF活性降低22.1%,纤维蛋白原未改变。化疗还导致K增加7.5%,延迟期延长8.6%,CLT缩短5.4%,而凝血酶生成未改变。扫描电子显微镜图像证实了化疗相关的凝块结构差异。化疗后纤维蛋白凝块特性在肺癌组织学类型、癌症分期或化疗方案之间没有差异。有趣的是,从不吸烟(n = 13,16%)与治疗后纤维蛋白结构更松散有关,表现为K升高12.3%。多元线性回归显示,癌症分期越晚、凝血酶生成峰值越高和白细胞计数越高决定了治疗后K的变化,而当前吸烟与CLT的变化有关。

结论

肺癌患者三个月的化疗尽管凝血酶生成未受影响,但改善了凝块特性,表明抗癌治疗可能会迅速产生抗血栓作用。

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