Platelet Inhibition in Shunted Infants on Aspirin at Short and Midterm Follow-Up

Abstract

There are few data to guide aspirin therapy to prevent shunt thrombosis in infants. We aimed to determine if aspirin administered at conventional dosing in shunted infants resulted in ≥50% arachidonic acid (AA) inhibition in short and midterm follow-up using thromboelastography with platelet mapping (TEG-PM) and to describe bleeding and thrombotic events during follow-up. We performed a prospective observational study of infants on aspirin following Norwood procedure, aortopulmonary shunt alone, or cavopulmonary shunt surgery. We obtained TEG-PM preoperatively, after the third dose of aspirin, at the first postoperative clinic visit, and 2-8 months after surgery. The primary outcome was the proportion of subjects with ≥50% AA inhibition on aspirin. All bleeding and thrombotic events were collected. Of 24 infants analyzed, 13% had ≥50% AA inhibition at all designated time points after aspirin initiation; 38% had ≥50% AA inhibition after the third aspirin dose of aspirin, 60% at the first postoperative clinic visit, and 26% 2-8 months after surgery. Bleeding events occurred in eight subjects, and two had a thrombotic event. Bleeding events were associated with greater AA inhibition just prior to starting aspirin (p = 0.02) and after the third dose of aspirin (p = 0.04), and greater ADP inhibition before surgery (p = 0.03). The majority of infants failed to consistently have ≥50% AA inhibition when checked longitudinally postoperatively. Preoperative TEG-PM may be useful in identifying infants at higher risk of bleeding events on aspirin in the early postoperative period. Further research is needed to guide antiplatelet therapy in this population.

Antiplatelet Therapy Monitoring in Neonates and Children

“…This review identified only two studies that reported a statistically significant association between thrombosis outcomes and laboratory values of responsiveness (urinary TxB2 and aspirin response unit), 16,18 and one study that reported a statistically significant association between bleeding and percentage of ADP inhibition (TEG-PM). 12 Notably, these are three observational cohort studies, but a meta-analysis and a systematic review in adults have previously established significant association between cardiovascular complications and resistance as defined by laboratory values. 2,3 Contrastingly, no studies included in this review illustrated or measured a change in clinical resistance after dose adjustments based on laboratory values.…”

“…Drug compliance was mentioned in 7/20 studies (35%) but not stated as the main purpose of utilizing the monitoring tools. 9,[11][12][13][14][15][16] Antiplatelet Biochemical Resistance and Response…”

“…Furthermore, the study found a significant association between greater percentage of AA and adenosine diphosphate (ADP) inhibition at different time points of measurement to bleeding. 12 Rosenthal et al compared monitoring in patients on ventricular-assist devices with two antiplatelet regimes across two time periods (aspirin and dipyridamole [before September 2012, TEG-PM-based doses] vs. aspirin, dipyridamole, and Clopidogrel [after September 2012, weight-based doses]). The study evaluated the outcome of dose titration by TEG-PM parameters, compared with dose titration by patient body weight.…”

Aspirin in childhood acute ischemic stroke: The evidence for treatment and efficacy testing

“…Gastrointestinal bleeding is attributed to both decreased prostaglandin synthesis in the gastric mucosa resulting in gastritis and an antiplatelet effect from irreversible COX1 inhibition. Pediatric data describing overall bleeding risks with ASA are limited, but the reported incidence ranges from 2% to 33%, with the highest risks associated with central venous catheter or chest tube sites after cardiac surgery . Pediatric estimates of ASA‐associated gastrointestinal bleeding are even more elusive, because most large studies address bleeding in side‐effect reporting rather than as a primary outcome .…”

“…Pediatric data describing overall bleeding risks with ASA are limited, but the reported incidence ranges from 2% to 33%, with the highest risks associated with central venous catheter or chest tube sites after cardiac surgery. 78,79 Pediatric estimates of ASA-associated gastrointestinal bleeding are even more elusive, because most large studies address bleeding in side-effect reporting rather than as a primary outcome. 80 shown in adults with coronary artery disease (CAD).…”