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Background: Many paediatric studies report that patients must be established on aspirin therapy for a minimum of 5 days to achieve adequate response. This is not always practical especially in critical settings. Prospective identification of patients that are unresponsive to aspirin sooner could potentially prevent thrombotic events., Aims: The aim of this study was to investigate prospectively if the first dose of aspirin is effective in decreasing platelet aggregation, and thromboxane formation and if this can be measured after 2 hours in paediatric cardiology patients. A secondary aim was to identify a cut-off for a novel marker of aspirin responsiveness the maximum amplitude with arachidonic acid, which could potentially dramatically reduce the blood volume required. Third, we aimed to prospectively identify potentially non-responsive patients by spiking a sample of their blood ex vivo with aspirin., Results: The majority (92.3%) of patients were responsive, when measured 2 hours post first dose of aspirin. Non-response or inadequate response (7.7%) can also be identified at 2 hours after taking the first dose of aspirin. Additionally, we have shown a novel way to reduce blood sample volume requirements by measurement of the maximum amplitude with arachidonic acid as a marker of response, particularly for monitoring., Conclusions: These findings of rapid efficacy in the majority of patients offer assurance in a sound, practical way to attending clinicians, patients, and families.

The optimal dose of aspirin required in children with congenital and acquired heart disease is not known. The primary aim of this prospective observational study was to evaluate the effects of aspirin dose on platelet inhibition. The secondary aim was to determine the prevalence and clinical predictors of aspirin non-responsiveness. Measurements were by Thromboelastography with Platelet Mapping (TEGPM) only in children less than 2 years (y) of age with particular emphasis on the parameter known as maximum amplitude with arachidonic acid (MAAA) and using both TEGPM, and light transmission aggregometry (LTA) in children greater than 2 y. We prospectively studied 101 patients with congenital and acquired cardiac disease who were receiving empirical doses of aspirin for a minimum of 4 weeks but no other antiplatelet agents. Patients were stratified according to dose concentration and age. There was a trend toward lower age in patients with no response or semi-response to aspirin. All patients were considered responsive to aspirin in the higher-dose quartile (Q4) with a median dose of 4.72 (4.18-6.05) mg/kg/day suggesting that patients in this age group may require 5 mg/kg/day as an empirical dose. In children > 2 y, there was no significant difference in inhibition found in patients dosed at higher doses in Q3 versus Q4 suggesting that patients in this cohort are responsive with 3 mg/kg/day dose. The current practices may lead to reduced platelet inhibition in some children due to under-dosing or overdosing in others. In conclusion, younger children require higher doses of aspirin. Laboratory assessment is warranted in this population to mitigate against under and overdosing., (© 2024. The Author(s).)

The aim of this study was to determine the rate of aspirin responsiveness in a cohort of pediatric patients with in situ xenograft valved right ventricle to pulmonary artery (RV-PA) conduits and/or transcatheter valve replacements (TVR). Aspirin is routinely prescribed to these patients. Optimizing anti-platelet therapy could promote valve longevity and reduce the risk of infective endocarditis in this at-risk group. This was a prospective, observational study. Patients were recruited from both ward and outpatient settings. Patients were eligible if under 18 years and taking aspirin. Non-response to aspirin was defined as > 20% platelet aggregation using light transmission platelet aggregometry (LTA) and < 50% platelet inhibition by thromboelastography with platelet mapping (TEGPM). Participants were invited to provide a confirmatory sample in cases of aspirin resistance and dose adjustments were made. Thirty patients participated. Median age was 9 years (2 months to 18 years). The majority (93%) had complex right ventricular outflow tract pathology. 13 (43%) had an RV-PA conduit and 24 (80%) had a TVR, with valve situated in conduit in 7 (23%) cases. Rate of aspirin non-response on initial testing was 23% (n = 7/30) with median LTA 74.55% (60-76%) and TEG 13.25% (0-44%) in non-responders. Non-responders were more likely to be under 1 year. Two patients required dose increases and one patient non-adherence to dose was identified. Four patients on repeat testing were responsive to aspirin by laboratory tests. The rate of aspirin non-response on laboratory testing in this cohort of patients was 23% and resulted in therapeutic intervention in 10%., (© 2024. The Author(s).)

Objective: A high platelet turnover rate may produce a population of platelets that confers an inadequate response to aspirin. We aimed to investigate the relationship between residual platelet aggregation and platelet turnover in paediatric cardiology patients on aspirin monotherapy by evaluating the fraction of immature platelets as a marker for turnover and secondly to test the predictive value of the immature platelet fraction (IPF) to classify patients as responsive or non-responsive to aspirin., Methods: Sixty patients divided into two age categories (≤90 days, >90 days of age) were included in this prospective observational study. Patients were then stratified into tertiles using their IPF level. Platelet studies included thromboelastography with platelet mapping (TEGPM)., Results: The overall incidence of 'inadequate response to aspirin' was 38 % in our patient cohort recently post-cardiac surgery a consequence that warrants further study. The frequency of inadequate response to aspirin was higher in the upper tertile of IPF when compared to the lower tertile, (88 %) versus (4 %) respectively (p < 0.05). The 'cut off' for IPF was determined to be 3.9 % with a sensitivity of 95.7 %, and a specificity of 92.9 % (area under the curve of 0.955 [CI 0.896-1.014, p < 0.05])., Conclusion: This study demonstrates that inadequate response to aspirin occurs in approximately 38 % of patients undergoing specific high-risk congenital cardiac procedures using the dosing practice of a national centre. This study supports the hypothesis that an elevated platelet turnover may result in aspirin being less effective in patients who are recently post cardiac surgery. These data are of direct translational relevance., Competing Interests: Declaration of competing interest There is no conflict of interest for any author. No author has any financial or personal relationship with other people or organisations that could inappropriately influence his/her work., (Copyright © 2023 Elsevier Ltd. All rights reserved.)