Abstract 16095: Is the Arachidonic Acid Pathway Adequately Inhibited in Shunted Infants on Aspirin?
Introduction: Prevention of shunt thrombosis is vital in infants who require a reliable source of pulmonary blood flow. Aspirin (ASA) prophylaxis is used to inhibit the platelet arachidonic acid (AA) pathway, but dosing is extrapolated from adults, and no therapeutic monitoring guidelines exist. We sought to determine the percentage of infants on ASA after shunt surgery with adequate AA inhibition using thromboelastography with platelet mapping (TEG-PM) and to describe adverse events (AE).
Methods: We performed a prospective observational study of infants treated with ASA after shunt (12/2012-5/2014). ASA was dosed at 3-5 mg/kg enterally starting postop day 1. TEG-PM was obtained at 5 intervals: 1) baseline (before cardiopulmonary bypass), 2) prior to 1st ASA dose, 3) after 3rd ASA dose, 4) 1st postop clinic visit, and 5) 2-6 months postop. Adequate AA inhibition was defined as ≥70%, the target parameter in the pediatric Berlin Heart protocol. Bleeding and thrombotic events were recorded as AEs. Clinicians were blinded to TEG-PM results. Fisher’s exact, t-test, and linear mixed model were used.
Results: The 25 subjects had cavopulmonary (N=11), aortopulmonary (N=9), and Sano (N=5) shunts; 9 (36%) were previously on ASA. Of the 20 who completed follow-up, 8 subjects had 13 AEs: 12 bleeding events (50% ≤7 days postop), 1 thrombotic stroke, and 0 shunt thrombosis. AA inhibition was ≥70% after the 3rd ASA dose in 10/21 (48%), at the 2 postop follow-ups in 4/15 (27%), and at all intervals on ASA in 1 (4%). ASA dose and time since dose were not associated with AA inhibition. Subjects with bleeding AEs had higher baseline ADP inhibition (76%±9 vs 44%±8, P=0.02), higher AA inhibition prior to 1st ASA dose (46%±22 vs 17%±15, P<0.01) and after the 3rd ASA dose (74%±20 vs 43%±33, P=0.04). TEG-PM nearest the bleeding AE (≤9 days) showed average ADP and AA inhibition of 76% and 51%.
Conclusions: AA inhibition was <70% in most shunted infants. No shunt thrombosis occurred but 1/3 had bleeding AEs, suggesting the target AA inhibition may be lower for the shunted infant. Increased ADP inhibition concomitant with AA inhibition predicted bleeding. Future studies will aim to determine the role of elevated ADP inhibition in bleeding risk and to determine the optimal AA target in this population.
Author Disclosures: D.T. Truong: None. J.T. Johnson: None. D.K. Bailly: None. J.R. Clawson: None. M.K. Witte: None. L. Minich: None.
- © 2014 by American Heart Association, Inc.