Activated factor XI-antithrombin and thrombin-antithrombin complexes in the prediction of venous thromboembolism and mortality in patients with non-small-cell lung cancer.

IF 5.5 2区医学 Q1 HEMATOLOGY

Journal of Thrombosis and Haemostasis Pub Date : 2025-03-06 DOI:10.1016/j.jtha.2025.02.029

Patricia Gomez-Rosas, Magdolna Nagy, Henry M H Spronk, Laura Russo, Sara Gamba, Carmen Julia Tartari, Silvia Bolognini, Chiara Ticozzi, Francesca Schieppati, Roberta Sarmiento, Filippo De Braud, Giovanna Masci, Carlo Tondini, Fausto Petrelli, Francesco Giuliani, Andrea D'Alessio, Armando Santoro, Giampietro Gasparini, Roberto Labianca, Hugo Ten Cate, Anna Falanga, Marina Marchetti

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引用次数: 0

Abstract

Background: Patients with non-small cell lung cancer (NSCLC) are at high risk of venous thromboembolism (VTE), especially during chemotherapy. Even though the contact system is implicated in the pathogenesis of thrombosis, limited data are available on the role of contact system activation in NSCLC-associated VTE.

Objectives: In a prospective cohort of patients with NSCLC starting chemotherapy, contact system activation and thrombin generation biomarkers were assessed in relation to 6-month VTE occurrence and mortality.

Methods: Prechemotherapy plasma samples of 719 newly diagnosed patients with NSCLC were tested for in vivo biomarkers of contact system activation (ie, kallikrein [pKa]:antithrombin [AT; PKa:AT], activated factor [F]XI:AT [FXIa:AT], FXIa:C1-esterase inhibitor C1Inh [FXIa:C1Inh], activated FIX:AT [FIXa:AT]), and thrombin generation (ie, prothrombin fragment 1+2 [F1+2] and thrombin-antithrombin complex [TAT]). Clinical data, VTE, and mortality were recorded prospectively.

Results: The 6-month VTE and mortality cumulative incidences were 11% and 27%, respectively. Basal levels of FXIa:AT complexes, F1+2, and TAT were higher in patients who developed VTE than those in VTE-free patients. Differently, PKa:AT, FIXa:AT, and TAT were lower in survivors than those in nonsurvivors. The multivariable analysis identified FXIa:AT (subdistribution hazard ratio, 1.17; 95% CI, 1.00-1.37) and TAT (subdistribution hazard ratio, 1.28; 95% CI, 1.10-1.50) as VTE-independent risk factors during chemotherapy. A score based on these biomarkers was generated, which was able to discriminate patients at significantly higher rates of VTE and mortality.

Conclusion: Elevated in vivo contact pathway activation and thrombin generation were observed in patients with NSCLC who developed VTE. Furthermore, a score based on both FXIa:AT and TAT levels was developed to identify those patients at higher risk of VTE and mortality.

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活化的fxi -抗凝血酶和凝血酶-抗凝血酶复合物在预测非小细胞肺癌患者静脉血栓栓塞和死亡率中的作用

背景：非小细胞肺癌（NSCLC）患者发生静脉血栓栓塞（VTE）的风险较高，尤其是在化疗期间。尽管接触系统与血栓形成的发病机制有关，但关于接触系统激活在非小细胞肺癌相关静脉血栓栓塞中的作用的数据有限。目的：在一个开始化疗的非小细胞肺癌患者的前瞻性队列中，接触系统激活和凝血酶生成生物标志物与6个月静脉血栓栓塞发生率和死亡率的关系进行了评估。方法：对719例新诊断的非小细胞肺癌患者化疗前血浆样本进行接触系统激活的体内生物标志物检测（即钾化likrein：抗凝血酶[PKa:AT]、活化的FXI:AT [FXIa:AT]、FXIa:c1酯酶抑制剂C1Inh [FXIa: C1Inh]、活化因子IX:AT [FIXa:AT]）和凝血酶生成（即凝血酶原片段1+2 [F1+2]、凝血酶-抗凝血酶复合物[TAT]）。前瞻性记录临床资料、静脉血栓栓塞和死亡率。结果：6个月静脉血栓栓塞和死亡累计发生率分别为11%和27%。VTE患者FXIa:AT复合物、F1+2和TAT的基础水平高于无VTE患者。不同的是，幸存者的PKa:AT、FIXa:AT和TAT比非幸存者低。多变量分析确定FXIa:AT （HR 1.17, 95%CI 1.00-1.37）和TAT （HR 1.28, 1.10-1.50）是化疗期间vte独立的危险因素。基于这些生物标志物的评分产生，能够区分静脉血栓栓塞和死亡率明显较高的患者。结论：发生静脉血栓栓塞的非小细胞肺癌患者体内接触途径激活和凝血酶生成升高。此外，基于FXIa:AT和TAT水平的评分被开发出来，以识别那些有较高静脉血栓栓塞和死亡率风险的患者。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Thrombosis and Haemostasis 医学-外周血管病

CiteScore

24.30

自引率

3.80%

发文量

321

审稿时长

1 months

期刊介绍： The Journal of Thrombosis and Haemostasis (JTH) serves as the official journal of the International Society on Thrombosis and Haemostasis. It is dedicated to advancing science related to thrombosis, bleeding disorders, and vascular biology through the dissemination and exchange of information and ideas within the global research community. Types of Publications: The journal publishes a variety of content, including: Original research reports State-of-the-art reviews Brief reports Case reports Invited commentaries on publications in the Journal Forum articles Correspondence Announcements Scope of Contributions: Editors invite contributions from both fundamental and clinical domains. These include: Basic manuscripts on blood coagulation and fibrinolysis Studies on proteins and reactions related to thrombosis and haemostasis Research on blood platelets and their interactions with other biological systems, such as the vessel wall, blood cells, and invading organisms Clinical manuscripts covering various topics including venous thrombosis, arterial disease, hemophilia, bleeding disorders, and platelet diseases Clinical manuscripts may encompass etiology, diagnostics, prognosis, prevention, and treatment strategies.