Malignancies, prothrombotic mutations, and the risk of venous thrombosis

JAMA. 2005 Feb 9;293(6):715-22. doi: 10.1001/jama.293.6.715.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Case-Control Studies
  • Factor V / genetics*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Neoplasm Metastasis
  • Neoplasms / blood
  • Neoplasms / complications*
  • Prothrombin / genetics*
  • Pulmonary Embolism / epidemiology
  • Pulmonary Embolism / etiology
  • Risk
  • Venous Thrombosis / epidemiology
  • Venous Thrombosis / etiology*

Substances

  • factor V Leiden
  • Factor V
  • Prothrombin