Aspirin unresponsiveness predicts thrombosis in high-risk pediatric patients after cardiac surgery

ObjectiveThrombosis occurs in up to 26% of patients with congenital heart disease after cardiac surgery and is associated with increased morbidity and mortality. Aspirin is commonly administered to reduce the risk of thrombosis, yet aspirin responsiveness is rarely assessed. In this study, we hypothesize that inadequate response to aspirin is associated with increased risk of thrombosis after selected congenital cardiac procedures considered to be high risk for thrombosis.MethodsPatients undergoing high-risk congenital cardiac surgery who received postoperative aspirin (N = 95) were studied. Response to aspirin was determined using the VerifyNow system several days after administration. Patients were monitored prospectively for 30 days for the development of a thrombosis event and the relationship between aspirin unresponsiveness and a thrombosis event was determined by the Fisher exact test.ResultsRate of aspirin unresponsiveness (≥550 aspirin reaction units [ARU]) was 10 of 95 (10.5%) and was highest in patients weighing less than 5 kg given 20.25 mg/d of aspirin. Thrombosis events occurred in 7 patients (7.4%). Thrombosis was observed in 6 of 10 (60%) patients who were unresponsive to aspirin, compared with 1 of 85 (1.2%) patients who were responsive to aspirin (P < .001). In 2 patients who were unresponsive to the initial aspirin dose, an increase in dose resulted in an adequate therapeutic aspirin response (ARU < 550), suggesting insufficiency rather than true resistance in a subset of patients.ConclusionsPostoperative thrombosis is associated with aspirin unresponsiveness in this patient population. In high-risk patients, monitoring of aspirin therapy and consideration of dose adjustment or alternative agents for unresponsive patients may be justified and warrants further investigation in a prospective trial

Intravenous GPIIb/IIIa Inhibitor for Secondary Prevention of Shunt Thrombosis in a Pediatric Patient

Thrombosis occurs after aortopulmonary shunting in children despite the use of heparin and oral antiplatelet agents. We describe the use of an intravenous antiplatelet agent for secondary prevention of shunt thrombosis without adverse events. Platelet mapping was used to monitor the effects and demonstrated the rapid onset of platelet inhibition

Transition from Hemochron Response to Hemochron Signature Elite Activated Clotting Time Devices in a Congenital Cardiac Surgery Practice

Heparin is the primary anticoagulant used during cardiac surgery to prevent thrombosis due to cardiopulmonary bypass (CPB)–related activation of the hemostatic system. The efficacy of heparin in the operating room is generally determined by activated clotting time (ACT) point-of-care tests performed throughout the procedure. In an effort to transition to the Hemochron Elite which requires approximately 1/10th the sampling volume of blood, we conducted a prospective study in 260 pediatric patients undergoing CPB. ACT tests were performed during CPB with a total of 260 pre-bypass and 1,117 on-bypass ACT values recorded. All samples were run simultaneously on both ACT devices. Several therapeutic cut-off possibilities ranging from >380 to >480 seconds were evaluated to ascertain the ACT level on the Elite device which best correlated with results from the Response device. Linear regression was used to determine correlation. The correlation between the two methods was moderate with a Pearson r of .6 and .4 for pre-bypass bolus ACT values and on-bypass ACT values, respectively. As the therapeutic ACT cut-off values were lowered from 480 to 380 seconds on the Elite device relative to the Response device (>480 seconds) for the on-bypass heparin samples, more patients would be under-dosed (incidence rising from 1 to 2%) and fewer patients would be overdosed (incidence decreasing from 32 to 5%) and the percent correlation between devices increased from 67 to 93%. A similar trend was observed with the pre-bypass heparin bolus samples. There was no significant effect of temperature on the ACT values comparing both devices. A therapeutic ACT value of >400 seconds for CPB with the Hemochron Elite device reasonably approximates a therapeutic ACT value of >480 seconds on the Hemochron Response device in our congenital cardiac surgery practice. Transitioning to the Elite device significantly reduces the overall sampling volume required for ACT monitoring during cardiac surgery

Transcriptome and epigenome landscape of human cortical development modeled in organoids

Genes implicated in neuropsychiatric disorders are active in human fetal brain, yet difficult to study in a longitudinal fashion. We demonstrate that organoids from human pluripotent cells model cerebral cortical development on the molecular level before 16 weeks postconception. A multiomics analysis revealed differentially active genes and enhancers, with the greatest changes occurring at the transition from stem cells to progenitors. Networks of converging gene and enhancer modules were assembled into six and four global patterns of expression and activity across time. A pattern with progressive down-regulation was enriched with human-gained enhancers, suggesting their importance in early human brain development. A few convergent gene and enhancer modules were enriched in autism-associated genes and genomic variants in autistic children. The organoid model helps identify functional elements that may drive disease onset