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Eur J Obstet Gynecol Reprod Biol. 2018 Feb;221:144-150. doi: 10.1016/j.ejogrb.2017.12.052. Epub 2018 Jan 1.

Aspirin non-responsiveness in pregnant women at high-risk of pre-eclampsia.

Author information

1
Centre for Women's Health Research, Institute of Translational Medicine, University of Liverpool, Crown Street, Liverpool, L8 7SS, UK. Electronic address: Kate.Navaratnam@liverpool.ac.uk.
2
The Wolfson Centre for Personalised Medicine, Institute of Translational Medicine, University of Liverpool, Brownlow Street, Liverpool, L69 3GL, UK.
3
Department of Biostatistics, Institute of Translational Medicine, University of Liverpool, L69 3GL, UK.
4
Centre for Women's Health Research, Institute of Translational Medicine, University of Liverpool, Crown Street, Liverpool, L8 7SS, UK.

Abstract

OBJECTIVES:

Low-dose aspirin is recommended for prevention of pre-eclampsia in high-risk pregnant women. Current doses provide a conservative risk reduction and some individuals demonstrate 'aspirin non-responsiveness', with insufficient antiplatelet effects. We aimed to determine if aspirin non-responsiveness could be identified in women at high risk of pre-eclampsia and assess for potential associations with placentally-mediated adverse outcomes.

STUDY DESIGN:

Prospective cohort study. 180 women at high-risk of pre-eclampsia, by NICE criteria, prescribed 75 mg dispersible aspirin daily were recruited from antenatal clinics of Liverpool Women's Hospital between 17/01/14 and 31/03/16. Platelet function (Multiplate™ impedance aggregometry, VerifyNow™ and 11-dehydrothromboxane B2) and aspirin metabolites (nuclear magnetic resonance and liquid chromatography mass spectrometry) were assessed at 5 + 0-20 + 6 and 33 + 0-35 + 6 weeks. Pearson's chi-square test was used to assess for associations between longitudinal response to aspirin and (1) any pre-eclampsia (2) composite adverse placentally-mediated outcome (one, or combination of pre-eclampsia, placental abruption, IUGR and perinatal mortality). A Bonferroni correction was applied to correct for multiple analyses.

RESULTS:

180 women were recruited, there were 4 withdrawals and no women were lost to follow-up. After 15 women delivered prior to the completion of follow-up, sufficient sample volumes for longitudinal platelet function and aspirin adherence testing were obtained from 156 women. There were no consistent aspirin non-responders in the cohort. 59% (n = 92) women exhibited normal response to aspirin, 34% (n = 53) variable response (switching response status between study visits) and in 7% (n = 11) response could not be determined as they exhibited lack of platelet response on a background of undetectable aspirin metabolites. There was no significant association between indeterminate or inconsistent (variable or indeterminate) response to aspirin and either pre-eclampsia (p = 0.59, p = 0.84) or composite outcome (p = 0.95, p = 0.65).

CONCLUSIONS:

When platelet function was assessed with COX-specific tests that measure the antiplatelet effects of low-dose aspirin and aspirin adherence is accurately accounted for aspirin non-responsiveness was not identified in pregnant women at high-risk of pre-eclampsia. Response to aspirin was not associated with placentally-mediated adverse outcomes. The high-degree of variable and indeterminate aspirin response indicates suboptimal adherence and/or dosing are more pressing factors to address to optimise aspirin effectiveness.

KEYWORDS:

Aspirin; Aspirin non-responsiveness; Aspirin resistance; Pre-eclampsia; Pregnancy

PMID:
29304392
DOI:
10.1016/j.ejogrb.2017.12.052
[Indexed for MEDLINE]

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