Platelet Responsiveness to Aspirin in Pediatric Patients Undergoing Cardiac Surgery - A Prospective Cohort Study

Abstract

Objective: Aspirin, at 3-5 mg/kg, is the cornerstone of thromboprophylaxis in pediatric cardiac surgery. The reported prevalence of aspirin unresponsiveness is 1-35% in adults and 10-15% in children. The aims of this study were: (1) Prevalence of aspirin responsiveness in the pediatric cardiac surgical population using light transmission aggregometry (LTA; gold standard) (2) Evaluate the dose-dependent response to aspirin (3) Compare LTA with point-of-care Thromboelastography with Platelet Mapping (TEG-PM) (4) Adverse events and risk factor analysis.

Methods: Prospective cohort study (Clinical Trials Registry ACTRN12618001879257) from 2022 to 2024 in a quaternary children's hospital in patients between 0 and 18 years of age who required aspirin prophylaxis after cardiac surgery. Patients who were allergic to aspirin or received other anticoagulants like 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 / ≥70% platelet aggregation to ADP denoted aspirin unresponsiveness. To evaluate TEG-PM as 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 re-evaluated. Those patients still not responding were labelled 'aspirin resistant'.

Results: There were 133 eligible patients [77 (58%) males, 49 (37%) single ventricle, 119 (89%) surgery using cardiopulmonary bypass]. 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 age was 1.9 years (IQR 0.13-12), and the median weight was 15.1 kg (IQR 4.2-44.1). Twenty-four (18%) patients did not respond to the standard aspirin dose. The dose was increased in 23 (17%) patients. Twenty (15%) patients were tested a second time. 13 (10%) patients 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 testing using LTA and TEG-PM (p=0.167). There were no identifiable risk factors for aspirin unresponsiveness.

Conclusion: 1/5th 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 necessary to define the utility of testing for aspirin responsiveness.

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