Abstract
Higher body mass index (BMI) is a risk factor for thrombosis. Platelets are essential for hemostasis but contribute to thrombosis when activated pathologically. We hypothesized that higher BMI leads to changes in platelet characteristics, thereby increasing thrombotic risk. The effect of BMI on platelet traits (measured by Sysmex) was explored in 33 388 UK blood donors (INTERVAL study). Linear regression showed that higher BMI was positively associated with greater plateletcrit (PCT), platelet count (PLT), immature platelet count (IPC), and side fluorescence (SFL, a measure of mRNA content used to derive IPC). Mendelian randomization (MR), applied to estimate a causal effect with BMI proxied by a genetic risk score, provided causal estimates for a positive effect of BMI on both SFL and IPC, but there was little evidence for a causal effect of BMI on PCT or PLT. Follow-up analyses explored the functional relevance of platelet characteristics in a pre-operative cardiac cohort (COPTIC). Linear regression provided observational evidence for a positive association between IPC and agonist-induced whole blood platelet aggregation. Results indicate that higher BMI raises the number of immature platelets, which is associated with greater whole blood platelet aggregation in a cardiac cohort. Higher IPC could therefore contribute to obesity-related thrombosis.
| Original language | English |
|---|---|
| Pages (from-to) | 869-878 |
| Number of pages | 10 |
| Journal | Platelets |
| Volume | 33 |
| Issue number | 6 |
| Early online date | 24 Jan 2022 |
| DOIs | |
| Publication status | Published - 24 Jan 2022 |
Bibliographical note
Funding Information:Participants in the INTERVAL randomised controlled trial were recruited with the active collaboration of NHS Blood and Transplant England ( www.nhsbt.nhs.uk ), which has supported field work and other elements of the trial. DNA extraction and genotyping was co-funded by the National Institute for Health Research (NIHR), the NIHR BioResource ( http://bioresource.nihr.ac.uk ) and the NIHR [Cambridge Biomedical Research Centre at the Cambridge University Hospitals NHS Foundation Trust]*. The academic coordinating centre for INTERVAL was supported by core funding from: NIHR Blood and Transplant Research Unit in Donor Health and Genomics (NIHR BTRU-2014-10024), UK Medical Research Council (MR/L003120/1), British Heart Foundation (SP/09/002; RG/13/13/30194; RG/18/13/33946) and the NIHR [Cambridge Biomedical Research Centre at the Cambridge University Hospitals NHS Foundation Trust]. A complete list of the investigators and contributors to the INTERVAL trial is provided in this reference []. The academic coordinating centre would like to thank blood donor centre staff and blood donors for participating in the INTERVAL trial. This work was supported by Health Data Research UK, which is funded by the UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, Department of Health and Social Care (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation and Wellcome. This work was also supported by the Wellcome Trust grant number 206194. *The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.
Publisher Copyright:
© 2021 The Author(s). Published with license by Taylor & Francis Group, LLC.
Keywords
- Aggregation
- epidemiology
- immature platelets
- Mendelian randomization
- obesity
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