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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 (PY) among sickle cell carriers and non-carriers; and adjusted OR for VTE among sickle cell carriers compared with non-carriers.
Results We included 30 424 individuals screened for sickle cell, with a follow-up time of 179 503 PY, identifying 55 VTEs in 6758 sickle cell carriers and 125 VTEs in 23 666 non-carriers. VTE incidence among sickle cell carriers (14.9/10 000 PY; 95% CI 11.4 to 19.4) was significantly higher than non-carriers (8.8/10 000 PY; 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 1775 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=0.006), with the greatest risk for pulmonary embolism (PE) (OR 2.27, 95% CI 1.17 to 4.39, p=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 PE, 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.
- sickle cell trait;
- Venous thromboembolism
- cohort study
This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
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Footnotes
Contributors NQ, JK, EO and YV are responsible for study conception and design. All authors are responsible for acquisition, analysis or interpretation of data. IL is responsible for drafting of the manuscript. NQ, JK, EO and YV are responsible for critical revision of the manuscript for important intellectual content. YV and IL are responsible for statistical analysis. NQ and JK obtained funding. All authors are responsible for administrative, technical or material support. NQ and EO are responsible for study supervision. All authors had full access to the data in the study and can take full responsibility for the integrity of the data and the accuracy of the data analysis.
Funding This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Ethics approval We obtained ethical approval from the CPRD Independent Scientific Advisory Committee of the UK Medicine and Healthcare products Regulatory Agency (protocol approval no. 13_097RA).
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement The authors confirm that, for approved reasons, some access restrictions apply to the data underlying the findings. Data are collected and owned and licensed by The Clinical Practice Research Datalink Group, The Medicines and Healthcare Products Regulatory Agency, 5th Floor, 151 Buckingham Palace Road, Victoria, London SW1W 9SZ, UK. Contact +44 20 3080 6383. See https://www.cprd.com/dataAccess/default.asp#OnlineDataGOLD