posted on 2022-01-24, 12:40authored byLucy J. Goudswaard, Laura J. Corbin, Kate L. Burley, Andrew Mumford, Parsa Akbari, Nicole Soranzo, Adam S. Butterworth, Nicholas A. Watkins, Dimitri J. Pournaras, Jessica Harris, Nicholas J. Timpson, Ingeborg Hers
<p>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.</p>
Funding
LJG is funded by the University of Bristol alumni on the 4-year BHF Integrative Cardiovascular Science PhD programme. LJC is funded by the Wellcome Trust (202802/Z/16/Z). KB is funded through a GW4-CAT Wellcome Trust Fellowship (216277/Z/19/Z). NS is supported by the Wellcome Trust, British Heart Foundation, and NIHR funding to the Cambridge Bioresource. JH is funded by the UK National Institute for Health Research through the Biomedical Research Centre at University Hospitals Bristol NHS Foundation Trust and the University of Bristol. IH is supported by the EPSRC Prostanoid programme (EP/M012530/1) and BHF (PG/16/3/31833). NJT is a Wellcome Trust Investigator (202802/Z/16/Z), is the PI of the Avon Longitudinal Study of Parents and Children (MRC & WT 102215/2/13/2), is supported by the University of Bristol NIHR Biomedical Research Centre (BRC-1215-20011), the MRC Integrative Epidemiology Unit (MC_UU_12013/3) and works within the CRUK Integrative Cancer Epidemiology Programme (C18281/A19169). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This research was funded in whole, or in part, by the Wellcome Trust (202802/Z/16/Z). For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.