Inherited Thrombophilia and the Risk of Venous Thromboembolism in Patients with Non-Small Cell Lung Cancer - Case-Control Study

Sep 30, 2026

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Venous thromboembolism (VTE) is a frequent cancer complication, particularly in lung cancer, yet the role of inherited thrombophilia in non-small cell lung cancer (NSCLC) remains insufficiently characterized. This observational, prospective case-control study enrolled 40 NSCLC patients (stages IIIB or IV), comparing 20 with VTE to 20 without VTE. Genotyping and functional assays assessed factor V Leiden, prothrombin mutation, antithrombin, protein C/S, and activated protein C resistance. Factor V Leiden appeared only in VTE cases.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages8

Reading Time20 min

AccessFree to download

Abstract

Background/Objectives

Methods

Results

Conclusions

Introduction

Methods

Study Design and Patient Selection

Inherited Thrombophilia and the Risk of Venous Thromboembolism in Patients with Non-Small Cell Lung Cancer, a Case-Control Study Clinical and Applied Thrombosis/Hemostasis Volume 32: 1-8 © The Author(s) 2026 Article reuse guidelines: [sagepub.com/journals-permissions](sagepub.com/journals-permissions)[ ](sagepub.com/journals-permissions)[DOI: 10.1177/10760296251399654](DOI: 10.1177/10760296251399654)[ ](DOI: 10.1177/10760296251399654)[journals.sagepub.com/home/cat](journals.sagepub.com/home/cat) José Costa, MD 1,2 , Margarida Carvalho, MD3, Emanuel Cadavez, MD4 , Jovita Gomes, PharmD 1, Rosário Pinto Leite, PhD5, and António Araújo, MD, PhD2,6 Abstract Background/Objectives: Venous thromboembolism (VTE) is a frequent complication of cancer, namely lung cancer. Many studies have been done searching for risk factors for VTE, but most don’t address the topic of inherited thrombophilia. The aim of this study is to evaluate the contribution of inherited thrombophilia to VTE in patients with NonSmall Cell Lung Cancer (NSCLC). Methods: This is an observational, prospective, case-control study, involving 40 patients with NSCLC, stages IIIB or IV, 20 with a diagnosis of VTE, and 20 with no VTE. Blood samples were collected for factor V and prothrombin genotyping, functional assays of antithrombin, protein C and protein S, and activated protein C resistance. All patients gave a signed informed consent, and the study was approved by the Ethics Committees of the Institutions involved. Results: The case and control groups were similar in terms of gender, age, Body Mass Index (BMI), stage or type of cancer. No patients were found with deﬁciencies of antithrombin or protein C, or with the prothrombin mutation. Factor V Leiden (FVL) was found in 2 patients from the case group, both with activated protein C resistance, and in none of the control group. Low levels of protein S were found in 2 patients from the control group and 1 from the case group. Conclusions: We conclude that FVL may be an important risk factor for VTE in patients with NSCLC. If these patients were screened for FVL, we could probably reduce the prevalence of VTE. Keywords venous thromboembolism, non-small cell lung cancer, inherited thrombophilia, factor V Leiden, prothrombin mutation, natural anticoagulants Received: 24 August 2025; revised: 13 October 2025; accepted: 4 November 2025 Introduction The association between cancer and venous thromboembolism (VTE) is well known since the ﬁrst description by Trousseau in 1865 1 The pathogenesis of cancerassociated VTE is multifactorial and complex involving multiple overlapping pathways.2 Some studies suggest inherited thrombophilia as an important risk factor for cancer-related VTE,3–5 but, apart from Acute Lymphoblastic Leukemia in children,6–8 there is much controversy on the contribution of thrombophilia to VTE in patients with malignancy.9 Lung cancer is among those with the highest rate of VTE (5.1%), next to pancreas (8.1%), and kidney 1 Department of Hematology and Transfusion Medicine, Unidade Local de Saúde de Trás-os-Montes e Alto Douro, Vila Real, Portugal 2School of Medicine and Biomedical Sciences – ICBAS, University of Porto, Porto, Portugal 3Department of Pulmonoloy, Unidade Local de Saúde de Trás-osMontes e Alto Douro, Vila Real, Portugal 4Department of Medical Oncology, Unidade Local de Saúde de Trás-osMontes e Alto Douro, Vila Real, Portugal 5Laboratory of Genetics, Unidade Local de Saúde de Trás-os-Montes e Alto Douro, Vila Real, Portugal 6Department of Medical Oncology, Unidade Local de Saúde de Santo António, Porto, Portugal Corresponding author: José Costa, Centro Hospitalar de Trás-os-Montes e Alto Douro (CHTMAD), Avenida da Noruega, Lordelo, 5000-508 Vila Real, Portugal. Email: [jcosta@chtmad.min-saude.pt](jcosta@chtmad.min-saude.pt) Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonComm

FAQs

What is the study’s main objective in NSCLC patients?

To evaluate how inherited thrombophilia contributes to VTE risk in patients with non-small cell lung cancer, focusing on factor V Leiden, prothrombin mutation, and deficiencies of natural anticoagulants.

How were participants selected for the case and control groups?

The study enrolled NSCLC patients aged 18 or older with stages IIIB or IV. The case group had VTE confirmed by imaging, while the control group had no history of thrombosis and was clinically stable.

Which inherited thrombophilia marker showed an association with VTE in the results?

Factor V Leiden was found in 2 patients in the VTE case group and in none of the control patients, leading to the conclusion that it may be an important VTE risk factor in NSCLC.

Sep 30, 2026

Uploaded by Fahsai