Platelet responsiveness to aspirin in pediatric patients undergoing cardiac surgery: A prospective cohort study

Abstract

Background: Aspirin at 3 to 5 mg/kg is the cornerstone of thromboprophylaxis in pediatric cardiac surgery. The reported prevalence of aspirin unresponsiveness is 1% to 35% in adults and 10% to 15% in children. The present study aimed to (1) describe the prevalence of aspirin responsiveness in the pediatric cardiac surgical population using light transmission aggregometry (LTA), the gold standard; (2) evaluate the dose-dependent response to aspirin; (3) compare LTA with point-of-care thromboelastography with platelet mapping (TEG-PM); and (4) describe adverse events and report a risk factor analysis.

Methods: This prospective cohort study (Clinical Trials Registry ACTRN12618001879257) was conducted from 2022 to 2024 in a quaternary children's hospital and included patients age 0 to 18 years who required aspirin prophylaxis after cardiac surgery. Patients who were allergic to aspirin or received other anticoagulants, such as warfarin, were excluded. Aspirin responsiveness was tested after at least 3 days of a standard aspirin dose of 5 mg/kg or 150 mg (whichever was less). LTA showing ≥20% platelet aggregation stimulated by arachidonic acid or ≥70% platelet aggregation to adenosine diphosphate denoted aspirin unresponsiveness. To evaluate TEG-PM compared to the gold standard (LTA), TEG-PM showing ≥50% platelet aggregation denoted aspirin unresponsiveness. The dose was increased to 10 mg/kg in these patients, and aspirin responsiveness was reevaluated. Those patients still not responding were labeled "aspirin-resistant."

Results: The 133 eligible patients included 77 males (58%), 49 with a single ventricle (37%), and 119 who underwent surgery using cardiopulmonary bypass (89%). The most common indications for aspirin were shunts/Fontan in single ventricle patients (n = 44; 33%) and valve repair/replacement (n = 25; 19%). The median patient age was 1.9 years (interquartile range [IQR], 0.13-12 years), and the median weight was 15.1 kg (IQR, 4.2-44.1 kg). Twenty-four patients (18%) did not respond to the standard aspirin dose, and the dose was increased in 23 patients (17%). Twenty patients (15%) were tested a second time; 13 (10%) responded to the increased aspirin dose (10 mg/kg). Seven patients (5%) were aspirin-resistant. There was no correlation between the results of aspirin responsiveness tested using LTA and TEG-PM (P = .167). There were no identifiable risk factors for aspirin unresponsiveness.

Conclusions: Almost 20% of pediatric cardiac surgical patients do not respond to a standard 5 mg/kg aspirin dose. Most non-responders have a dose-dependent response to aspirin. Only 5% of patients are genuinely aspirin-resistant (as defined by LTA). TEG-PM does not correlate with the gold standard LTA test to determine aspirin responsiveness. Testing for aspirin responsiveness should be considered in patients undergoing pediatric cardiac surgery who are at risk of clinically significant thrombosis; however, further evidence with correlation to clinical outcomes is needed to define the utility of testing for aspirin responsiveness.

Keywords: aspirin responsiveness; pediatric cardiac surgery; platelets; thrombosis.