Malignancies, Prothrombotic Mutations, and the Risk of Venous Thrombosis

TLDR

Venous thrombosis is a frequent complication in cancer patients, contributing to morbidity and reduced quality of life. The study aimed to identify cancer patients at elevated thrombotic risk by evaluating tumor site, presence of distant metastases, and carrier status of prothrombotic mutations. A population‑based case‑control study of 3,220 cancer patients and 2,131 controls collected questionnaire data and performed genetic testing for factor V Leiden and prothrombin 20210A three months after anticoagulant discontinuation. Cancer patients had a seven‑fold higher risk of venous thrombosis, with hematologic malignancies showing the greatest risk (OR ≈ 28), early post‑diagnosis periods and distant metastases conferring the highest odds (up to OR ≈ 53), and carriers of factor V Leiden or prothrombin 20210A mutations experiencing markedly increased risk.

Abstract

Venous thrombosis is a common complication in patients with cancer, leading to additional morbidity and compromising quality of life.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.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.Risk of venous thrombosis.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.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.