Prospective study of sickle cell trait and venous thromboembolism incidence

J Thromb Haemost. 2015 Jan;13(1):2-9. doi: 10.1111/jth.12787. Epub 2014 Dec 11.

Abstract

Background: Sickle cell trait may increase risk of venous thromboembolism, but this is not fully established.

Objectives: We sought to determine the association of sickle cell trait with deep vein thrombosis and pulmonary embolism.

Methods: Middle-aged African Americans participating in a prospective, population-based cohort investigation, the Atherosclerosis Risk in Communities Study, were followed from 1987 through 2011 for incident hospitalized pulmonary embolism (n = 111) or isolated deep vein thrombosis (n = 138), verified by physician review of medical records. Sickle cell trait (heterozygosity for hemoglobin S, n = 268) was compared with no sickle cell trait (n = 3748).

Results: Over a median of 22 years of follow-up, 249 participants had an incident venous thromboembolism. The hazard ratio of venous thromboembolism was 1.50 (95% confidence interval [CI] 0.96-2.36) for participants with vs. without sickle cell trait, after adjustment for age, sex, ancestry, hormone replacement therapy (women), body mass index, diabetes, and estimated glomerular filtration rate. This hazard ratio was 2.05 (95% CI 1.12-3.76) for pulmonary embolism and 1.15 (95% CI 0.58-2.27) for deep vein thrombosis without pulmonary embolism.

Conclusions: Sickle cell trait in African Americans carries a 2-fold increased risk of pulmonary embolism but does not elevate deep vein thrombosis risk. Because neonatal screening for sickle hemoglobin is being conducted in the United States, consideration should be paid to the increased pulmonary embolism risk of individuals with sickle cell trait.

Keywords: epidemiology; prospective study; risk factors; sickle cell trait; venous thromboembolism.

Publication types

  • Multicenter Study
  • Research Support, American Recovery and Reinvestment Act
  • Research Support, N.I.H., Extramural

MeSH terms

  • African Americans* / genetics
  • Female
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Prospective Studies
  • Pulmonary Embolism / diagnosis
  • Pulmonary Embolism / ethnology*
  • Risk Assessment
  • Risk Factors
  • Sickle Cell Trait / diagnosis
  • Sickle Cell Trait / ethnology*
  • Sickle Cell Trait / genetics
  • Time Factors
  • United States / epidemiology
  • Venous Thromboembolism / diagnosis
  • Venous Thromboembolism / ethnology*
  • Venous Thrombosis / diagnosis
  • Venous Thrombosis / ethnology*