Fionnuala Mone, Juhi K Gupta, Marie M Phelan, Shireen Meher, Lu Yung Lian, Ben Francis, Eunice Zhang, Cecilia Mulcahy, Ana Alfirevic, Fionnuala M Mcauliffe, Kate Navaratnam
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Platelet response to aspirin in UK and Irish pregnancy cohorts: a genome-wide approach.
A multi-center prospective cross-sectional and genome-wide association study (GWAS) recruited pregnant women taking low dose aspirin. Objectives were to (i) develop pregnancy-specific 95% reference intervals for a range of laboratory based platelet function tests (PFTs); (ii) select an optimal and acceptable PFT that reflected aspirin's COX-1 inhibition in women with confirmed aspirin adherence in pregnancy; and (iii) identify genomic variants that may influence pregnant women's platelet response to aspirin.The study included two independent cohorts of pregnant women. A range of PFTs and matched phenotyping with urinary 11-dehydrothromboxane B2 (11DTXB2) and nuclear magnetic resonance (NMR) spectroscopy detection of urinary salicyluric acid as a measure of aspirin adherence were performed. Genome-wide data was acquired from the UK Biobank Axiom® (Thermo Fisher Scientific). 11DTXB2 in combination with adherence testing with NMR salicyluric acid was an accurate and acceptable testing strategy for detecting biochemical aspirin responsiveness in pregnant women, with the provision of relevant reference ranges. GWAS meta-analysis found no significant single nucleotide polymorphisms in association with response to aspirin in pregnancy. Further evaluation in relation to effective dosing of aspirin in pregnancy and optimizing the benefits to specific subgroups should now be a priority for future research.
期刊介绍:
Platelets is an international, peer-reviewed journal covering all aspects of platelet- and megakaryocyte-related research.
Platelets provides the opportunity for contributors and readers across scientific disciplines to engage with new information about blood platelets. The journal’s Methods section aims to improve standardization between laboratories and to help researchers replicate difficult methods.
Research areas include:
Platelet function
Biochemistry
Signal transduction
Pharmacology and therapeutics
Interaction with other cells in the blood vessel wall
The contribution of platelets and platelet-derived products to health and disease
The journal publishes original articles, fast-track articles, review articles, systematic reviews, methods papers, short communications, case reports, opinion articles, commentaries, gene of the issue, and letters to the editor.
Platelets operates a single-blind peer review policy. Authors can choose to publish gold open access in this journal.