Familial Clustering of Venous Thromboembolism - A Danish Nationwide Cohort Study

PLoS One. 2016 Dec 29;11(12):e0169055. doi: 10.1371/journal.pone.0169055. eCollection 2016.

Abstract

Background: Identification of risk factors for venous thromboembolism (VTE) is of utmost importance to improve current prophylactic regimes and treatment guidelines. The extent to which a family history contributes to the risk of VTE needs further exploration.

Objectives: To examine the relative rate of VTE in first-degree relatives compared with the general population.

Methods: By crosslinking Danish nationwide registries we identified patients with VTE between 1978 and 2012, and their familial relations. The first member in a family to acquire VTE was defined as the proband. All first-degree relatives to probands were followed from the VTE date of the proband and until an event (VTE), death, emigration, 100 year birthday or end of study: 31st of December 2012, whichever came first. The relative rate of VTE was estimated by standardized incidence ratios (SIR) using time-dependent Poisson regression models, with the general population as a fixed reference.

Results: We identified 70,767 children of maternal probands, 66,065 children of paternal probands, and 29,183 siblings to sibling probands. Having a maternal proband or a paternal proband were associated with a significantly increased VTE rate of 2.15 (CI: 2.00-2.30) and 2.06 (CI: 1.92-2.21), respectively. The highest estimate of VTE was observed among siblings (adjusted SIR of 2.60 [CI: 2.38-2.83]). Noteworthy, the rate of VTE increased for all first-degree relatives when the proband was diagnosed with VTE in a young age (≤ 50 years).

Conclusion: A family history of VTE was associated with a significantly increased rate of VTE among first-degree relatives compared with the general population.

MeSH terms

  • Adult
  • Aged
  • Cohort Studies
  • Denmark / epidemiology
  • Female
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Pedigree*
  • Risk Factors
  • Venous Thromboembolism / diagnosis
  • Venous Thromboembolism / epidemiology*

Grants and funding

This study was funded by a grant from the Danish Council of Independent Research (grant no. 4183-00008). Dr. Gislason is supported by an unrestricted clinical research scholarship from the Novo Nordisk Foundation. The funders had no role in the design and the conduct of the study; the collection, management, analyses, and interpretation of the data; the preparation or approval of this manuscript; or in the decision to submit the manuscript for publication.