Aspirin in Children with Congenital and Acquired Cardiac Disease: Paediatric study of Aspirin Efficacy using Diagnostic and Monitoring Tools (PAED-M)

While the primary physiological function of aspirin in children with acquired or congenital heart disease is to prevent platelet aggregation and hence thrombosis, its effect is rarely monitored, and the phenomenon of aspirin resistance or non-responsiveness is widely debated. Moreover, the potential of the interplay between aspirin and platelets to provide novel opportunities for measurement is increasing. The work described within this thesis was conducted to explore and characterise the effects of aspirin therapy in children whether it be the first dose, patients who are post-surgery or patients on long-term aspirin therapy. The study employed robust methodologies to ensure confidence in results and reviewed other methods to optimise the pathway for children by substitution of lower volume tests. Patients who are recently post-surgery have a higher rate of inadequate response to aspirin than those on long-term aspirin and without recent surgery. A high platelet turnover rate was found to produce a population of platelets that may confer an inadequate response to aspirin. The relationship between residual platelet aggregation and platelet turnover in paediatric cardiology patients on aspirin monotherapy was investigated by evaluating the fraction of immature platelets. Eventhough, there was a higher response rate in patients on long-term aspirin, children less than 2 years of age were found to require more aspirin possibly up to 5mg/kg/day. Results are also presented that demonstrate that the majority of patients were responsive to aspirin (92.3%), and this can be measured at 2 hours post aspirin dosing. Non-response or inadequate response (7.7%) can also be identified at 2 hours after taking the first dose of aspirin. These findings of rapid efficacy in a high percentage of patients offer assurance in a sound, practical way to attending clinicians, the patient, and their families. This study also consolidates our hypothesis that the majority of children are responsive to aspirin but extra vigilance by monitoring should be undertaken post events such as surgery, infection, and dose change. Additionally, we have shown a novel way to reduce blood sample volume requirements by measuring the TEG parameter, maximum amplitude induced by arachidonic acid (MA AA) as a response marker, particularly for monitoring. In summary, the crosstalk between cardiology and the antiplatelet effects informs clinical practice in cardiology and indeed platelet disorders. The in vitro results described in this thesis may, if replicated in vivo, represent a means of addressing significant dilemmas in both paediatric cardiology, and platelet inhibition and pave the way for future studies and clinical trials.