Venous thromboembolism in adults screened for Sickle Cell Trait: a population based cohort study with nested case-control analysis

Little, Iain; Vinogradova, Yana; Orton, Elizabeth; Kai, Joe; Qureshi, Nadeem

Abstract

Objective: To determine whether sickle cell carriers (‘sickle cell trait’) have an increased risk of venous thromboembolism (VTE).


Design: Cohort study with nested case-control analysis.
Setting: General population with data from 609 UK general practices in the Clinical Practice Research Datalink (CPRD).


Participants: All individuals registered with a CPRD general practice between 1998 and 2013, with a medical record of screening for sickle cell between 18 and 75 years of age.

Main outcomes measures: Incidence of VTE per 10,000 person-years among sickle cell carriers and non-carriers; and adjusted odds ratio (OR) for VTE among sickle cell carriers compared to non-carriers.

Results: We included 30,424 individuals screened for sickle cell, with a follow-up time of 179,503 person-years, identifying 55 VTEs in 6,758 sickle cell carriers and 125 VTEs in 23,666 non-carriers. VTE incidence amongst sickle cell carriers (14.9/10,000 person-years; 95% CI: 11.4 to 19.4) was significantly higher than non-carriers (8.8/10,000 person-years; 95% CI: 7.4 to 10.4). Restricting analysis to confirmed non-carriers was non-significant, but performed on a small sample. In the case-control analysis (180 cases matched to 1,775 controls by age and gender), sickle cell carriers remained at increased risk of VTE after adjusting for body mass index, pregnancy, smoking status and ethnicity (OR 1.78, 95% CI: 1.18 to 2.69, p-value 0.006 ), with the greatest risk for pulmonary embolism (OR 2.27, 95% CI: 1.17 to 4.39, p-value 0.011).
Conclusions: Although absolute numbers are small, in a general population screened for sickle cell, carriers have a higher incidence and risk of VTE, particularly pulmonary embolism, than non-carriers. Clinicians should be aware of this elevated risk in the clinical care of sickle cell carriers, or when discussing carrier screening, and explicitly attend to modifiable risk factors for VTE in these individuals. More complete primary care coding of carrier status could improve analysis.

Citation

Little, I., Vinogradova, Y., Orton, E., Kai, J., & Qureshi, N. (2017). Venous thromboembolism in adults screened for Sickle Cell Trait: a population based cohort study with nested case-control analysis. BMJ Open, 7(3), Article e012665. https://doi.org/10.1136/bmjopen-2016-012665

• Journal Article Type: Article
• Acceptance Date: Feb 3, 2017
• Online Publication Date: Mar 29, 2017
• Publication Date: Mar 1, 2017
• Deposit Date: Feb 21, 2017
• Publicly Available Date: Mar 1, 2017
• Journal: BMJ Open
• Electronic ISSN: 2044-6055
• Publisher: BMJ Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 7
• Issue: 3
• Article Number: e012665
• DOI: https://doi.org/10.1136/bmjopen-2016-012665
• Public URL: https://nottingham-repository.worktribe.com/output/843049
• Publisher URL: http://bmjopen.bmj.com/content/7/3/e012665
• Contract Date: Feb 21, 2017