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Malignancies, Prothrombotic Mutations, and the Risk of Venous Thrombosis
Abstract
CONTEXT: Venous thrombosis is a common complication in patients with cancer, leading to additional morbidity and compromising quality of life. OBJECTIVE: To identify individuals with cancer with an increased thrombotic risk, evaluating different tumor sites, the presence of distant metastases, and carrier status of prothrombotic mutations. DESIGN, SETTING, AND PATIENTS: A large population-based, case-control (Multiple Environmental and Genetic Assessment [MEGA] of risk factors for venous thrombosis) study of 3220 consecutive patients aged 18 to 70 years, with a first deep venous thrombosis of the leg or pulmonary embolism, between March 1, 1999, and May 31, 2002, at 6 anticoagulation clinics in the Netherlands, and separate 2131 control participants (partners of the patients) reported via a questionnaire on acquired risk factors for venous thrombosis. Three months after discontinuation of the anticoagulant therapy, all patients and controls were interviewed, a blood sample was taken, and DNA was isolated to ascertain the factor V Leiden and prothrombin 20210A mutations. MAIN OUTCOME MEASURE: Risk of venous thrombosis. RESULTS: The overall risk of venous thrombosis was increased 7-fold in patients with a malignancy (odds ratio [OR], 6.7; 95% confidence interval [CI], 5.2-8.6) vs persons without malignancy. Patients with hematological malignancies had the highest risk of venous thrombosis, adjusted for age and sex (adjusted OR, 28.0; 95% CI, 4.0-199.7), followed by lung cancer and gastrointestinal cancer. The risk of venous thrombosis was highest in the first few months after the diagnosis of malignancy (adjusted OR, 53.5; 95% CI, 8.6-334.3). Patients with cancer with distant metastases had a higher risk vs patients without distant metastases (adjusted OR, 19.8; 95% CI, 2.6-149.1). Carriers of the factor V Leiden mutation who also had cancer had a 12-fold increased risk vs individuals without cancer and factor V Leiden (adjusted OR, 12.1; 95% CI, 1.6-88.1). Similar results were indirectly calculated for the prothrombin 20210A mutation in patients with cancer. CONCLUSIONS: Patients with cancer have a highly increased risk of venous thrombosis especially in the first few months after diagnosis and in the presence of distant metastases. Carriers of the factor V Leiden and prothrombin 20210A mutations appear to have an even higher risk.
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“Fibrinolytic therapy helps in dissolving fibrins in occluded vessels and improving the tumor vasculature [32,33,34,35,36].”
From Approaches to Improve EPR-Based Drug Delivery for Cancer Therapy and Diagnosis (2023) · cites this paper as [33]
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Metadata
- Authors
- Blom, J. W.
- Affiliations
- Leiden University Medical Center (NL)
- Corresponding author
- Blom, Jeanet W.
- ORCID
- Blom, Jeanet W.
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2005-02-09
- Volume
- 293
- Issue
- 6
- Pages
- 715
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- OpenAlex
- W2007086823
- Cited by
- 1,949
- References
- 26
- Citations by year
- 2026: 49 · 2025: 66 · 2024: 96 · 2023: 89 · 2022: 123 · 2021: 124 · 2020: 106 · 2019: 112 · 2018: 121 · 2017: 106 · 2016: 98 · 2015: 122 · 2014: 92 · 2013: 96 · 2012: 100
- FWCI
- 48.38
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- University of Twente Research Information (publishedVersion)
- University of Twente Research Information (submittedVersion)
- Topics
- Health Sciences › Medicine › Internal Medicine › Venous Thromboembolism Diagnosis and Management
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Health Sciences › Medicine › Clinical Neurology › Cerebral Venous Sinus Thrombosis
- Keywords
- venous thrombosis, cancer-associated thrombosis, prothrombotic mutations, factor V Leiden, deep vein thrombosis, pulmonary embolism, hematologic malignancies, lung cancer, gastrointestinal cancer, distant metastasis, thrombosis risk factors, cancer survivors, anticoagulation clinic, MEGA
- MeSH terms
- Adult, Aged, Factor V, Female, Humans, Male, Middle Aged, Mutation, Neoplasm Metastasis, Neoplasms, Prothrombin, Pulmonary Embolism, Risk, Case-Control Studies, Venous Thrombosis
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