Aspirin Responsiveness in a Cohort of Paediatric Patients With Bovine Jugular Venous Valves and Right Ventricle to Pulmonary Artery Conduits

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Kelleher, Irene E. Regan, Dermot Cox, Kathryn Shaw, Damien P. Kenny, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3244339/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 15 Mar, 2024 Read the published version in Pediatric Cardiology → Version 1 posted 9 You are reading this latest preprint version Abstract Objective: The aim of this study was to determine the rate of aspirin responsiveness in a cohort of paediatric patients with in-situ xenograft valved right ventricle to pulmonary artery (RV-PA) conduits and/or bovine jugular venous valves (BJV). Aspirin is routinely prescribed to these patients. Optimising anti-platelet therapy could promote valve longevity and reduce the risk of infective endocarditis in this at-risk group. Materials and Methods: This was a prospective, observational study. Patients were recruited from both ward and outpatient settings. Patients were eligible if under 18 years and taking aspirin. Non-response to aspirin was defined as >20% platelet aggregation using light-transmission platelet aggregometry (LTA) and <50% platelet inhibition by thromboelastography with platelet mapping (TEGPM). Participants were invited to provide a confirmatory sample in cases of aspirin resistance and dose adjustments were made. Results: Thirty patients participated. Median age was 9 years (2 months – 18 years). The majority (93%) had complex right ventricular outflow tract pathology. 13 (43%) had an RV-PA conduit, 24 (80%) had a BJV, with valve situated in conduit in 7 (23%) cases. Rate of aspirin non-response on initial testing was 23% (n=7/30) with median LTA 25.45% (24.9-40%) and TEG 13.25% (0-44%) in non-responders. Non-responders were more likely to be under 1 year. Two patients required dose increases and one patient non-adherence to dose was identified. In 4 patients repeat testing revealed normal results. Conclusions The rate of aspirin non-response on laboratory testing in this cohort of patients was 23% and resulted in therapeutic intervention in 10%. Aspirin conduit jugular venous valve platelet resistance thrombosis Figures Figure 1 INTRODUCTION Aspirin possesses a myriad of biological effects, one of its most pertinent being its ability to inhibit platelet aggregation. Achieved through its irreversible inhibition of the cyclo-oxygenase-1 (COX-1) enzyme, aspirin limits the access of arachidonic acid to a key site on COX-1, attenuating the downstream production of thromboxane A2 (TXA2), a powerful platelet aggregator. The effect of aspirin therefore lasts the lifespan of the platelet [ 1 ]. Aspirin non-responsiveness is defined as the inability of aspirin to decrease the production of thromboxane A2 and prevent platelet aggregation in a laboratory test. It may arise through a variety of mechanisms including under-dosing, drug-drug interactions, increased platelet turnover and genetic polymorphisms [ 2 ]. The first report of bovine jugular valved right ventricle to pulmonary artery (RV-PA) conduits used in animal studies dates from 1992 [ 3 ]. Since then, valved RV-PA conduits, including the Contegra® (bovine) and HancockⓇ (porcine) conduits, have become widely used surgical options to treat complex forms of right ventricular outflow tract obstruction in the paediatric population [ 4 , 5 ]. Over time, such conduits may become stenotic or develop valvar insufficiency requiring replacement. Transcatheter pulmonary valve replacement (TPVR) with stent mounted bovine jugular venous valves (BJV) has in recent years offered an alternative to surgical conduit replacement. The first such valve, the MelodyⓇ, was approved by the FDA in 2010 [ 6 ], and additionally there is now widespread experience with both the Edwards SAPIENⓇ valve and the Venus-P system [ 7 , 8 ]. Increasingly, BJV are being utilised in the mitral and tricuspid positions [ 9 , 10 ]. Mid- and long-term outcomes post TPVR are favourable with survival 91% and freedom from intervention 75% at 8 years [ 11 ]. However, the evidence suggests that the incidence of infective endocarditis (IE) with the use of BJV systems is higher than with other valve types (homograft and bioprosthetic valves) [ 12 ]. The annualised incidence of IE post TPVR is 2.2 per 100 patient years [ 13 ]. While aspirin appears to be routinely prescribed amongst these patients, there is a paucity of prescribed guidelines for the optimal use of anti-coagulant and anti-platelet agents in patients with an RV-PA conduit or TPVR. A recent survey of interventionalists demonstrated that post TPVR, 100% prescribed aspirin, but there was a wide variation in dosing, and use of additional agents [ 14 ]. While thromboembolic events are certainly low in this group [ 15 ], a recent series of explanted valved conduits demonstrated very high rates of sub-clinical thrombus adherent to the valve sinuses, the presence of which may contribute to valve failure and act as a nidus for IE [ 16 ]. Furthermore, abrupt discontinuation of aspirin has been highlighted as a potential risk factor for the development of IE in patients with Melody® valve in situ [ 17 ]. There have been calls to further clarify the role of aspirin and anti-platelet agents in mitigating the risk of IE and valve failure [ 13 , 16 ]. There have been no previous studies of failure to respond to aspirin in this context and most practitioners do not routinely test for it [ 14 ]. Our aim was to determine the rate of aspirin non-response in a cohort of paediatric patients with in-situ xenograft valved-conduits and bovine jugular venous valves. METHODS Patient selection This study was approved by The Research and Ethics Committee of Children’s Health Ireland at Crumlin, Dublin, Ireland (GEN/580/17). This study formed part of a larger study on aspirin response in paediatric patients with congenital heart disease. Written informed parental consent was obtained for each participant. All patients were attending cardiac services at Children’s Health Ireland at Crumlin. Recruitment took place between January 2019 and June 2023. Patients were included if they had an in-situ RV-PA xenograft valved-conduit or a bovine jugular venous valve system and were taking aspirin. Exclusion criteria are listed in table 1. Table 1 – Exclusion Criteria Patients were prospectively enrolled from both ward and outpatient settings. Aspirin was dosed at 3-5mg/kg, up to a maximum of 75mg. Institutional practice is to prescribe to the nearest quarter of a 75mg tablet due to the inaccuracy of dispersion techniques with such preparations [18]. Testing Aspirin response was tested a minimum of two hours post first dose of aspirin, with most patients on established aspirin therapy at time of testing. If non-response was detected, adherence and dose timing were discussed. Participants were invited to provide a confirmatory sample. Dose adjustments, if deemed appropriate, were made in consultation with the primary physician and typically increased in quarter tablet (of 75mg) increments. Aspirin response was measured using two separate tests described below: Thromboelastography with Platelet Mapping (TEGPM) and Light-Transmission Platelet Aggregation (LTA). For patients under the age of 2 years, TEGPM alone was performed due to the phlebotomy requirements for completion of both tests. Thromboelastography with Platelet Mapping (TEGPM) TEGPM was performed using a platelet mapping assay on the TEGâ 5000 analyser platform. This gives a quantitative analysis of platelet function based on the formation, strength, and degradation of clots in whole blood. It allows for the contribution of aspirin to be assessed through the addition of arachidonic acid (AA) to determine the response of the TXA2 receptor when compared with standard samples from the index patient. Three assays were performed. The first was performed by adding whole blood to kaolin and measuring TEG on this kaolin-activated blood to derive maximal clot strength (MAThrombin) in the standard TEG fashion. The contribution of fibrin to clot strength (MAFibrin) was assessed through the addition of reptilase and factor XII and measured on a second TEG cup. Finally, arachidonic acid (AA) and Activator F were added to a sample in a third TEG cup to assess the contribution of the COX-1 pathway (MA AA). The percentage platelet inhibition was calculated using the equation 100-{(MA AA –MA Fibrin) / (MA Thrombin –MA Fibrin) X 100}. Non-responsiveness to aspirin was defined as platelet inhibition <50%. Light-Transmission Platelet Aggregometry (LTA) LTA was performed on platelet rich plasma samples by placing the sample between the light-source and the photocell. Arachadonic acid was added to the sample in order to activate platelets. Aspirin non-response was defined as platelet aggregation in response to arachidonic acid of >20%. Statistical analysis Baseline and demographic data were summarised for the enrolled patients. Normally distributed continuous data are expressed as mean ± SD, non-normally distributed variables were expressed as median (minimum-maximum). Categorical variables were expressed as percentages. Comparison of characteristics between responders and non-responders was performed using the Mann-Whitney U test for continuous variables, and Fisher exact test for categorical data. Statistical analysis was performed using GraphPad Prism version 10.0.0. RESULTS Demographic characteristics In total, 30 patients were recruited to participate. Demographic data as listed in Table 2 . Median age was 9 with a broad range of age groups represented with the youngest participant aged 2 months. The most common single diagnosis was pulmonary atresia (PA), a heterogenous group which included patients with intact ventricular septum, ventricular septal defect and major aorto-pulmonary collateral arteries (MAPCAS) who had undergone biventricular repair. Also included were patients with BJVs in the mitral (n = 1, Melody®) and tricuspid (n = 1, Edwards SAPIENⓇ) positions. Table 2 – Demographics and patient characteristics Total n = 30 Age (years) - < 1 year - 1–4 years - 5–10 years - 11–18 years 9 (0.17-18) - 2 (7) - 5 (17) - 9 (30) - 14 (46) Sex - Female - Male - 19 (63) - 11 (37) Primary Diagnosis - Pulmonary atresia o w/ VSD, MAPCAS o w/ VSD o w/ ccTGA - Tetralogy of Fallot - Complex TGA - Truncus Arteriosus - Pulmonary stenosis - Mitral regurgitation - 12 (40) o 6 (20) o 4 (13) o 2 (7) - 11 (37) - 3 (10) - 2 (7%) - 1 (3%) - 1 (3%) RV-PA Conduit - Contegra - Hancock 13 (43) - 11 (37) - 2 (7) Bovine Jugular Venous Valves - Melody - Edwards SAPIEN - Edwards Perimount Valve Position - Native/patched RVOT - RV-PA Conduit - Mitral Position - Tricuspid Position 24 (80) - 19 (63) - 4 (13) - 1 (3) - 15 (50) - 7 (23) - 1 (3) - 1 (3) Testing setting - Outpatient - Post-operative period - Post-interventional procedure - 20 (67) - 4 (13) - 6 (20) Lifetime history of infective endocarditis 4 (13) Median aspirin dose/kg 2.93mg/kg/day (0.54–5.35) Values are Median (minimum to maximum), n(%), unless otherwise stated. TGA = Transposition of the great arteries , RV−PA = right ventricle to pulmonary artery, RVOT = right ventricular outflow tract Test results There were 30 initial tests and 9 instances of repeat testing. In the majority of cases (82%) both TEGPM and LTA were performed. Two patients had two repeat tests performed. There was good agreement between the tests. There was one occurrence of discordant testing in which the patient was classified as being responsive by LTA (10.4%) and having a low response by TEGPM (30.1%). Seven (23%) of patients demonstrated non-response to prescribed aspirin therapy as defined by TEGPM and/or LTA on initial testing. Laboratory test results are detailed in Table 3 . There was no statistically significant difference between the median age of the two groups, but non-responders were more likely to be under 1 year. There were no statistically significant differences between the baseline characteristics and testing context between the two groups (out-patient vs. post-operative or post-procedural). Table 3 – Laboratory Test Results Testing points - TEG-PM - LTA - Both n = 39 - 37 (95) - 34 (87) - 32 (82) Non-responsive on initial testing 7 (23) Discordant testing 1 (3) LTA (median) responsive 8.45% (0.7–20%) TEGPM (median) responsive 100% (64–100%) LTA (median) non-responsive 25.45% (24.9–40%) TEGPM (median) non-responsive 13.25% (0–44%) Values are Median (minimum to maximum), n(%), unless otherwise stated, SD = standard deviation, TEG−PM = Thrombo−elastography with platelet mapping, LTA = light transmission platelet aggregometry Table 4 – Comparison of Characteristics of Responders and Non-responders Non-responders (n = 7) Responders (n = 23) p-value Age* (years) 2.75 (0.2–13) 10 (2–18) 0.076 Under 1 year 2 (29) 0 (0) 0.048 Weight* (kg) 16 (4–50) 27 (6–69) 0.133 Normalised dose (mg/kg) 4.29 (1.5–5.35) 2.63 (0.54–4.87) 0.066 Post-op 1 (14) 3 (13) > 0.99 Post-procedure 0 (0) 6 (26) 0.29 Values are Median (minimum to maximum), n(%), unless otherwise stated. * parameters assessed using Mann Whitney U Test, remaining parameters assessed used Figher’s Exact test. Outcomes of patients demonstrating aspirin non-response The baseline characteristics and outcomes of the 7 patients demonstrating inadequate response to aspirin (non-response) on initial testing are outlined in Table 5 . Where there was an initial abnormal test result, patients were invited to return for repeat confirmatory testing. In case 5, repeat testing was not performed, and aspirin dose was increased at the discretion of the attending physician. Six patients had repeat testing performed, and in 5 of the 6 cases, the repeat test was normal. In case 1, non-adherence with the prescribed dose was identified. In case 2, the initial sample was taken in-hospital in the post-operative setting. Repeat testing beyond the post operative period demonstrated normal response. In case 3 no cause was identified. In case 4, test timing may be implicated with the previous dose had been taken 24 hours before the sample. In case 7 there was discordant testing which was no longer apparent on repeat (described above). In case 6, aspirin non-response was identified on an appropriate dose on sequential testing that resolved on dose increase. Table 5 – Outcomes of patients demonstrating aspirin non-response No. Diagnosis Conduit/ Valve Age (yrs) Weight (kg) Dose (mg) TEGPM (%) LTA (%) Test repeated Repeat result Outcome 1 Pulmonary atresia RV-PA Conduit 2 18 75 26.5 24 yes Normal Adherence discussed 2 Pulmonary atresia RV-PA Conduit 0.75 8.5 37.5 0 - pending Normal Attributed to post-operative period 3 Pulmonary atresia BJV in RV-PA Conduit 12 50 75 43 40 yes Normal No change No cause identified 4 Pulmonary stenosis BJV (pulmonary) 2 14 75 0 26 yes Normal Dose timing 5 Tetralogy of Fallot BJV (pulmonary) 11 - 75 0 24.9 no - Dose increase 6 Truncus Arteriosus RV-PA Conduit 0.17 4 18.75 44.5 - yes Resistant Dose increase. 7 Complex TGA BJV (tricuspid) 12 42 75 30.4 10.4 yes Normal Resolution of discordant testing on repeat TEGPM = thromboelastography with platelet mapping, LTA = light transmission platelet aggregometry, RV−PA = Right ventricle to pulmonary artery, BJV = Bovine jugular venous valve, TGA = transposition of the great arteries DISCUSSION Summary In this prospectively recruited observational series, this is the first time that the rate of aspirin non-responsiveness amongst patients with BJV systems and xenograft valved conduits has been reported. An initial rate of aspirin non-responsiveness of 23% was identified in this group. However, in 17% (n = 5) of patients repeat confirmatory testing at a separate time point was normal, with non-adherence to the correct dose of aspirin confirmed in 3% (n = 1). The true rate of aspirin non-responsiveness requiring dose increase in this group may be as low as 6.7%. In 10% (n = 3), testing for aspirin response resulted in a therapeutic intervention consisting of dose increases in two cases and medication education in another. Non-responders were more likely to be under the age of 1 (29% vs 0%). Of the two non-responders under 1, one was in the post-operative period. Increased vigilance in this age group may be advised. Agreement between tests was strong, which if consideration was made to adoption of testing to routine practice would decrease phlebotomy requirements. Repeat testing is recommended for instances of discordance. Previous studies of paediatric patients with congenital heart disease have demonstrated rates of aspirin non-responsiveness between 10–50% [ 19 – 22 ]. Some of the variation in reported rates may be attributable to the context in which testing was performed with previous literature largely focusing on the post-operative period, which appears to be a high-risk period for decreased response and often in those with single ventricle physiology. For example, rates of up to 80% have been identified, in the early post operative period in neonates and infants following first stage surgical palliation for single ventricle physiology [ 23 ]. Additionally, cardiopulmonary bypass appears to impact rates of aspirin non-responsiveness [ 24 ]. Inadequate response to aspirin in post-operative paediatric patients with CHD, has been demonstrated to be associated with higher mortality from thrombotic events [ 20 ]. Furthermore, testing for aspirin response in the post-operative period and intervening with dose increases has been shown to lower rates of thrombotic events [ 19 ]. However, in the context of BJV systems and xenograft valved conduits, the role that aspirin non-responsiveness may play in valve longevity and risk of IE has not been demonstrated. This is the first study to explore the rate of aspirin non- responsiveness in this context, with further studies being necessary to explore the link between inadequate response and adverse outcomes. A strength of this study is that confirmatory testing was requested prior to therapeutic changes and interestingly a proportion of patients initially deemed non-responsive were responsive on repeat. In adult series, pharmacokinetic resistance is frequently identified in such cases. Pharmacokinetic resistance signifies low plasma levels of aspirin despite adequate intake. Frequently prescribed enteric-coated preparations can have significant effects on bio-availability and are the norm unless specified by the prescribing physician [ 25 – 28 ]. Concurrent use of NSAIDs, and proton-pump inhibitors can also affect bioavailability [ 14 ]. Adherence with medication has been implicated in adult studies on aspirin resistance [ 29 ], but adherence may be underestimated in the paediatric population [ 30 ]. Pharmacodynamic resistance in which there is adequate bioavailability of aspirin but no inhibition in-vitro appears to be rare, especially that which cannot be overcome by dose increase [ 2 , 19 , 25 , 26 , 28 ]. Limitations This is a small, single-centre observational study, without control group for comparison. This study was not powered to assess whether aspirin non-responsiveness was associated with adverse outcomes in this group of patients. Not assessed by this study is the link between genetic polymorphisms and inadequate response to aspirin. Gene polymorphisms in dual antiplatelet therapy may be associated with the presence of leaflet thickening after transcatheter aortic valve replacement [ 31 ], but this has not been demonstrated post TPVR. Notable in this series is the rate of prior IE of 13% indicating that this is certainly a high-risk group. However, this is not indicative of IE within the study period and inferences between aspirin response and IE could not be drawn. The variable response to aspirin in some patients over time is not fully understood. False positive test results need to be considered. However, in an effort to mitigate against this, all patients were analysed by employing two assays where possible. A surrogate agonist AA was substituted into the TEG assay to confirm TEG results. All analysis was repeated on the same samples using the initial two assays to confirm results. Therefore, fluctuations in response may be due to non-adherence or pharmacokinetics (typically attributed to enteric coated preparations or drug-drug interactions). The implications of fluctuating response to aspirin are not known. Conclusions The rate of aspirin non-responsiveness amongst paediatric patients with bovine jugular venous valve systems or xenograft valved conduits was 24% and testing for aspirin response should be considered in these patients. However, only 6.7% of patients required dose increases. The authors recommend reviewing aspirin dose regularly and up-titrating dose for weight, with consideration for responsiveness testing with dose increases particularly under the age of 1 year. Increased vigilance for non-response in the post operative period has been previously shown to reduce thrombotic events [ 19 ]. Where non-response is identified, confirmation of adherence and additional medications should be reviewed. The authors advocate for the prescription of non-enteric coated preparations. A testing algorithm has been proposed (Fig. 1 ). Whether aspirin possesses a protective effect against the development of IE and valve failure in these patients remains to be fully elucidated. Echoing the call from previous literature, there is a need for clear guidance on the optimal anti-platelet regimen in this patient cohort [ 13 , 14 , 16 ]. Declarations Acknowledgements: The authors would like to thank the patients and their families who participated in this study. Special thanks to Jennie Ryan, Molly O’Toole, Rachel Birmingham, Jackie Campion, Nicky Smith, and Ciara Sheridan of the Cardiac Day Unit at Children’s Health Ireland for all their help with study. In addition, we would like to thank Dr. Michaeala Pentony for her help with study recruitment. Author Contributions: All authors contributed to the manuscript. Sean T. Kelleher and Irene E. Regan collated the data and wrote the first draft. Dermot Cox, Kathryn Shaw, Orla Franklin, Damien P. Kenny and Kevin P. Walsh edited the manuscript and made important amendments to the manuscript including extensive points of discussion. Colin J. McMahon devised the study, helped collate data, edited and submitted the manuscript. Competing interests: The authors have no relevant financial interests to disclose. Damien P. Kenny is a member of the editorial board of Pediatric Cardiology. Funding support: This study was supported by an institutional grant as part of a Clinical Research Fellowship for IER from the National Children’s Research Centre, Ireland. Data Sharing Agreement: Data available on request. Compliance with Ethical Standards: The study protocol was approved by the Ethics department at Children’s Health Ireland (CHI) Crumlin Dublin Ireland (GEN/580/17). The study complied with the Declaration of Helsinki for medical research involving human subjects. 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J Thromb Thrombolysis 45(3):463–465 Additional Declarations Competing interest reported. The authors have no relevant financial interests to disclose. Damien P. Kenny is a member of the editorial board of Pediatric Cardiology. Cite Share Download PDF Status: Published Journal Publication published 15 Mar, 2024 Read the published version in Pediatric Cardiology → Version 1 posted Editorial decision: Revision requested 18 Dec, 2023 Reviews received at journal 28 Sep, 2023 Reviews received at journal 24 Sep, 2023 Reviewers agreed at journal 21 Sep, 2023 Reviewers agreed at journal 19 Sep, 2023 Reviewers invited by journal 18 Sep, 2023 Editor assigned by journal 09 Aug, 2023 Submission checks completed at journal 09 Aug, 2023 First submitted to journal 08 Aug, 2023 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3244339","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":225229778,"identity":"8884aee9-735b-4919-8f5f-023de4b1a89c","order_by":0,"name":"Sean T. Kelleher","email":"","orcid":"","institution":"Children’s Health Ireland at Crumlin","correspondingAuthor":false,"prefix":"","firstName":"Sean","middleName":"T.","lastName":"Kelleher","suffix":""},{"id":225229779,"identity":"9d0c4d24-4ee1-44a5-86d9-6007930b2b90","order_by":1,"name":"Irene E. Regan","email":"","orcid":"","institution":"Children’s Health Ireland at Crumlin","correspondingAuthor":false,"prefix":"","firstName":"Irene","middleName":"E.","lastName":"Regan","suffix":""},{"id":225229780,"identity":"e361acd3-5dba-42ab-a85b-8b945ecbcbff","order_by":2,"name":"Dermot Cox","email":"","orcid":"","institution":"Royal College of Surgeons Ireland","correspondingAuthor":false,"prefix":"","firstName":"Dermot","middleName":"","lastName":"Cox","suffix":""},{"id":225229781,"identity":"7eac0fc6-4f07-469d-b473-48568c2fe474","order_by":3,"name":"Kathryn Shaw","email":"","orcid":"","institution":"Children’s Health Ireland at Crumlin","correspondingAuthor":false,"prefix":"","firstName":"Kathryn","middleName":"","lastName":"Shaw","suffix":""},{"id":225229782,"identity":"9b89de8e-b1d6-4afa-ad9c-343292aec508","order_by":4,"name":"Damien P. Kenny","email":"","orcid":"","institution":"Children’s Health Ireland at Crumlin","correspondingAuthor":false,"prefix":"","firstName":"Damien","middleName":"P.","lastName":"Kenny","suffix":""},{"id":225229783,"identity":"bc0c4c7b-3d07-4eb2-bae0-039837c09389","order_by":5,"name":"Kevin P. Walsh","email":"","orcid":"","institution":"Children’s Health Ireland at Crumlin","correspondingAuthor":false,"prefix":"","firstName":"Kevin","middleName":"P.","lastName":"Walsh","suffix":""},{"id":225229784,"identity":"f220d707-b6c3-4ede-99a1-f88632428650","order_by":6,"name":"Orla Franklin","email":"","orcid":"","institution":"Children’s Health Ireland at Crumlin","correspondingAuthor":false,"prefix":"","firstName":"Orla","middleName":"","lastName":"Franklin","suffix":""},{"id":225229785,"identity":"f83a66b2-5f3f-41ef-aff7-80782a5f5f59","order_by":7,"name":"Colin J. McMahon","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/0lEQVRIiWNgGAWjYLACxgYGBn725gMHEnhsGBgkiNUi2XMs8cEHmTQStBjcyDE2nGFzmLAW/mmHn274ucMmz+BGgpk0T875xP7ZzQcfMNTYROPSInE7zexm75m0YskzD9Kkec7cTpxx51iyAcOxtNwGHFoMpHPYbvC2HU7sO55wTJq353Ziw40cMwnGhsN4tdz8C9TScCCxTZr337nE+cRouQ2yZcKJZGbDGTwHEjcQ0gLyy23ZtrTEmT3HGB984Ek23ngjLdkgAY9f+GcnP7v5ts0msZ+9/wMwKu1k591IPvjgQ40NTi0YwBGsMoFY5SBgT4riUTAKRsEoGBkAAJ28aK1VwLJcAAAAAElFTkSuQmCC","orcid":"","institution":"Children’s Health Ireland at Crumlin","correspondingAuthor":true,"prefix":"","firstName":"Colin","middleName":"J.","lastName":"McMahon","suffix":""}],"badges":[],"createdAt":"2023-08-08 06:59:27","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3244339/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3244339/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00246-024-03449-1","type":"published","date":"2024-03-15T15:01:13+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":41637121,"identity":"690fcc27-5d64-4278-ab25-56a61fcc2a02","added_by":"auto","created_at":"2023-08-16 13:53:11","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":130127,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eProposed Aspirin Responsiveness Testing Algorithm\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"Fig1.png","url":"https://assets-eu.researchsquare.com/files/rs-3244339/v1/f8b5c6f365eff51480a27700.png"},{"id":52907562,"identity":"b29e6053-35ab-4d4d-b713-b8e18901081b","added_by":"auto","created_at":"2024-03-18 15:13:25","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":633036,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3244339/v1/423a8679-33ee-4db5-80c2-6d98c664c8aa.pdf"}],"financialInterests":"Competing interest reported. The authors have no relevant financial interests to disclose. Damien P. Kenny is a member of the editorial board of Pediatric Cardiology.","formattedTitle":"\u003cp\u003eAspirin Responsiveness in a Cohort of Paediatric Patients With Bovine Jugular Venous Valves and Right Ventricle to Pulmonary Artery Conduits\u003c/p\u003e","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eAspirin possesses a myriad of biological effects, one of its most pertinent being its ability to inhibit platelet aggregation. Achieved through its irreversible inhibition of the cyclo-oxygenase-1 (COX-1) enzyme, aspirin limits the access of arachidonic acid to a key site on COX-1, attenuating the downstream production of thromboxane A2 (TXA2), a powerful platelet aggregator. The effect of aspirin therefore lasts the lifespan of the platelet [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Aspirin non-responsiveness is defined as the inability of aspirin to decrease the production of thromboxane A2 and prevent platelet aggregation in a laboratory test. It may arise through a variety of mechanisms including under-dosing, drug-drug interactions, increased platelet turnover and genetic polymorphisms [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe first report of bovine jugular valved right ventricle to pulmonary artery (RV-PA) conduits used in animal studies dates from 1992 [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Since then, valved RV-PA conduits, including the Contegra\u0026reg; (bovine) and HancockⓇ (porcine) conduits, have become widely used surgical options to treat complex forms of right ventricular outflow tract obstruction in the paediatric population [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Over time, such conduits may become stenotic or develop valvar insufficiency requiring replacement. Transcatheter pulmonary valve replacement (TPVR) with stent mounted bovine jugular venous valves (BJV) has in recent years offered an alternative to surgical conduit replacement. The first such valve, the MelodyⓇ, was approved by the FDA in 2010 [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], and additionally there is now widespread experience with both the Edwards SAPIENⓇ valve and the Venus-P system [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Increasingly, BJV are being utilised in the mitral and tricuspid positions [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Mid- and long-term outcomes post TPVR are favourable with survival 91% and freedom from intervention 75% at 8 years [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. However, the evidence suggests that the incidence of infective endocarditis (IE) with the use of BJV systems is higher than with other valve types (homograft and bioprosthetic valves) [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. The annualised incidence of IE post TPVR is 2.2 per 100 patient years [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e While aspirin appears to be routinely prescribed amongst these patients, there is a paucity of prescribed guidelines for the optimal use of anti-coagulant and anti-platelet agents in patients with an RV-PA conduit or TPVR. A recent survey of interventionalists demonstrated that post TPVR, 100% prescribed aspirin, but there was a wide variation in dosing, and use of additional agents [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. While thromboembolic events are certainly low in this group [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], a recent series of explanted valved conduits demonstrated very high rates of sub-clinical thrombus adherent to the valve sinuses, the presence of which may contribute to valve failure and act as a nidus for IE [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Furthermore, abrupt discontinuation of aspirin has been highlighted as a potential risk factor for the development of IE in patients with Melody\u0026reg; valve in situ [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThere have been calls to further clarify the role of aspirin and anti-platelet agents in mitigating the risk of IE and valve failure [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. There have been no previous studies of failure to respond to aspirin in this context and most practitioners do not routinely test for it [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Our aim was to determine the rate of aspirin non-response in a cohort of paediatric patients with in-situ xenograft valved-conduits and bovine jugular venous valves.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003e\u003cstrong\u003ePatient selection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by The Research and Ethics Committee of Children\u0026rsquo;s Health Ireland at Crumlin, Dublin, Ireland (GEN/580/17). This study formed part of a larger study on aspirin response in paediatric patients with congenital heart disease. Written informed parental consent was obtained for each participant. All patients were attending cardiac services at Children\u0026rsquo;s Health Ireland at Crumlin. Recruitment took place between January 2019 and June 2023. Patients were included if they had an in-situ RV-PA xenograft valved-conduit or a bovine jugular venous valve system and were taking aspirin. Exclusion criteria are listed in table 1.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 1 \u0026ndash; Exclusion Criteria\u003c/p\u003e\n\u003cp\u003e\u003cimg 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\"\u003e\u003c/p\u003e\n\u003cp\u003ePatients were prospectively enrolled from both ward and outpatient settings. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAspirin was dosed at 3-5mg/kg, up to a maximum of 75mg. Institutional practice is to prescribe to the nearest quarter of a 75mg tablet due to the inaccuracy of dispersion techniques with such preparations [18].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTesting\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAspirin response was tested a minimum of two hours post first dose of aspirin, with most patients on established aspirin therapy at time of testing. If non-response was detected, adherence and dose timing were discussed. Participants were invited to provide a confirmatory sample. Dose adjustments, if deemed appropriate, were made in consultation with the primary physician and typically increased in quarter tablet (of 75mg) increments. Aspirin response was measured using two separate tests described below: Thromboelastography with Platelet Mapping (TEGPM) and Light-Transmission Platelet Aggregation (LTA). For patients under the age of 2 years, TEGPM alone was performed due to the phlebotomy requirements for completion of both tests.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eThromboelastography with Platelet Mapping (TEGPM)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTEGPM was performed using a platelet mapping assay on the TEG\u0026acirc; 5000 analyser platform. This gives a quantitative analysis of platelet function based on the formation, strength, and degradation of clots in whole blood. It allows for the contribution of aspirin to be assessed through the addition of arachidonic acid (AA) to determine the response of the TXA2 receptor when compared with standard samples from the index patient. Three assays were performed. The first was performed by adding whole blood to kaolin and measuring TEG on this kaolin-activated blood to derive maximal clot strength (MAThrombin) in the standard TEG fashion. The contribution of fibrin to clot strength (MAFibrin) was assessed through the addition of reptilase and factor XII and measured on a second TEG cup. Finally, arachidonic acid (AA) and Activator F were added to a sample in a third TEG cup to assess the contribution of the COX-1 pathway (MA AA). The percentage platelet inhibition was calculated using the equation 100-{(MA AA \u0026ndash;MA Fibrin) / (MA Thrombin \u0026ndash;MA Fibrin) X 100}. Non-responsiveness to aspirin was defined as platelet inhibition \u0026lt;50%.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLight-Transmission Platelet Aggregometry (LTA)\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLTA was performed on platelet rich plasma samples by placing the sample between the light-source and the photocell. Arachadonic acid was added to the sample in order to activate platelets. Aspirin non-response was defined as platelet aggregation in response to arachidonic acid of \u0026gt;20%.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistical analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eBaseline and demographic data were summarised for the enrolled patients. Normally distributed continuous data are expressed as mean \u0026plusmn; SD, non-normally distributed variables were expressed as median (minimum-maximum). Categorical variables were expressed as percentages. Comparison of characteristics between responders and non-responders was performed using the Mann-Whitney U test for continuous variables, and Fisher exact test for categorical data. Statistical analysis was performed using GraphPad Prism version 10.0.0.\u0026nbsp;\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eDemographic characteristics\u003c/h2\u003e \u003cp\u003eIn total, 30 patients were recruited to participate. Demographic data as listed in Table \u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Median age was 9 with a broad range of age groups represented with the youngest participant aged 2 months. The most common single diagnosis was pulmonary atresia (PA), a heterogenous group which included patients with intact ventricular septum, ventricular septal defect and major aorto-pulmonary collateral arteries (MAPCAS) who had undergone biventricular repair. Also included were patients with BJVs in the mitral (n\u0026thinsp;=\u0026thinsp;1, Melody\u0026reg;) and tricuspid (n\u0026thinsp;=\u0026thinsp;1, Edwards SAPIENⓇ) positions.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e\u0026ndash; Demographics and patient characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal n\u0026thinsp;=\u0026thinsp;30\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003cp\u003e- \u003cem\u003e\u0026lt;\u0026thinsp;1 year\u003c/em\u003e\u003c/p\u003e \u003cp\u003e- \u003cem\u003e1\u0026ndash;4 years\u003c/em\u003e\u003c/p\u003e \u003cp\u003e- \u003cem\u003e5\u0026ndash;10 years\u003c/em\u003e\u003c/p\u003e \u003cp\u003e- \u003cem\u003e11\u0026ndash;18 years\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (0.17-18)\u003c/p\u003e \u003cp\u003e- \u003cem\u003e2 (7)\u003c/em\u003e\u003c/p\u003e \u003cp\u003e- \u003cem\u003e5 (17)\u003c/em\u003e\u003c/p\u003e \u003cp\u003e- \u003cem\u003e9 (30)\u003c/em\u003e\u003c/p\u003e \u003cp\u003e- \u003cem\u003e14 (46)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003cp\u003e- \u003cem\u003eFemale\u003c/em\u003e\u003c/p\u003e \u003cp\u003e- \u003cem\u003eMale\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e- \u003cem\u003e19 (63)\u003c/em\u003e\u003c/p\u003e \u003cp\u003e- \u003cem\u003e11 (37)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrimary Diagnosis\u003c/p\u003e \u003cp\u003e- \u003cem\u003ePulmonary atresia\u003c/em\u003e\u003c/p\u003e \u003cp\u003eo \u003cem\u003ew/ VSD, MAPCAS\u003c/em\u003e\u003c/p\u003e \u003cp\u003eo \u003cem\u003ew/ VSD\u003c/em\u003e\u003c/p\u003e \u003cp\u003eo \u003cem\u003ew/ ccTGA\u003c/em\u003e\u003c/p\u003e \u003cp\u003e- \u003cem\u003eTetralogy of Fallot\u003c/em\u003e\u003c/p\u003e \u003cp\u003e- \u003cem\u003eComplex TGA\u003c/em\u003e\u003c/p\u003e \u003cp\u003e- \u003cem\u003eTruncus Arteriosus\u003c/em\u003e\u003c/p\u003e \u003cp\u003e- \u003cem\u003ePulmonary stenosis\u003c/em\u003e\u003c/p\u003e \u003cp\u003e- \u003cem\u003eMitral regurgitation\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e- \u003cem\u003e12 (40)\u003c/em\u003e\u003c/p\u003e \u003cp\u003eo \u003cem\u003e6 (20)\u003c/em\u003e\u003c/p\u003e \u003cp\u003eo \u003cem\u003e4 (13)\u003c/em\u003e\u003c/p\u003e \u003cp\u003eo \u003cem\u003e2 (7)\u003c/em\u003e\u003c/p\u003e \u003cp\u003e- \u003cem\u003e11 (37)\u003c/em\u003e\u003c/p\u003e \u003cp\u003e- \u003cem\u003e3 (10)\u003c/em\u003e\u003c/p\u003e \u003cp\u003e- \u003cem\u003e2 (7%)\u003c/em\u003e\u003c/p\u003e \u003cp\u003e- \u003cem\u003e1 (3%)\u003c/em\u003e\u003c/p\u003e \u003cp\u003e- \u003cem\u003e1 (3%)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRV-PA Conduit\u003c/p\u003e \u003cp\u003e- \u003cem\u003eContegra\u003c/em\u003e\u003c/p\u003e \u003cp\u003e- \u003cem\u003eHancock\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (43)\u003c/p\u003e \u003cp\u003e- \u003cem\u003e11 (37)\u003c/em\u003e\u003c/p\u003e \u003cp\u003e- \u003cem\u003e2 (7)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBovine Jugular Venous Valves\u003c/p\u003e \u003cp\u003e- \u003cem\u003eMelody\u003c/em\u003e\u003c/p\u003e \u003cp\u003e- \u003cem\u003eEdwards SAPIEN\u003c/em\u003e\u003c/p\u003e \u003cp\u003e- \u003cem\u003eEdwards Perimount\u003c/em\u003e\u003c/p\u003e \u003cp\u003eValve Position\u003c/p\u003e \u003cp\u003e- \u003cem\u003eNative/patched RVOT\u003c/em\u003e\u003c/p\u003e \u003cp\u003e- \u003cem\u003eRV-PA Conduit\u003c/em\u003e\u003c/p\u003e \u003cp\u003e- \u003cem\u003eMitral Position\u003c/em\u003e\u003c/p\u003e \u003cp\u003e- \u003cem\u003eTricuspid Position\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24 (80)\u003c/p\u003e \u003cp\u003e- \u003cem\u003e19 (63)\u003c/em\u003e\u003c/p\u003e \u003cp\u003e- \u003cem\u003e4 (13)\u003c/em\u003e\u003c/p\u003e \u003cp\u003e- \u003cem\u003e1 (3)\u003c/em\u003e\u003c/p\u003e \u003cp\u003e- \u003cem\u003e15 (50)\u003c/em\u003e\u003c/p\u003e \u003cp\u003e- \u003cem\u003e7 (23)\u003c/em\u003e\u003c/p\u003e \u003cp\u003e- \u003cem\u003e1 (3)\u003c/em\u003e\u003c/p\u003e \u003cp\u003e- \u003cem\u003e1 (3)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTesting setting\u003c/p\u003e \u003cp\u003e- \u003cem\u003eOutpatient\u003c/em\u003e\u003c/p\u003e \u003cp\u003e- \u003cem\u003ePost-operative period\u003c/em\u003e\u003c/p\u003e \u003cp\u003e- \u003cem\u003ePost-interventional procedure\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e- \u003cem\u003e20 (67)\u003c/em\u003e\u003c/p\u003e \u003cp\u003e- \u003cem\u003e4 (13)\u003c/em\u003e\u003c/p\u003e \u003cp\u003e- \u003cem\u003e6 (20)\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLifetime history of infective endocarditis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (13)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMedian aspirin dose/kg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.93mg/kg/day (0.54\u0026ndash;5.35)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003csup\u003e\u003cb\u003eValues are Median (minimum to maximum), n(%), unless otherwise stated. TGA = Transposition of the great arteries\u003c/b\u003e,\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e\u003csup\u003e\u003cb\u003eRV\u0026minus;PA = right ventricle to pulmonary artery, RVOT = right ventricular outflow tract\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eTest results\u003c/h2\u003e \u003cp\u003eThere were 30 initial tests and 9 instances of repeat testing. In the majority of cases (82%) both TEGPM and LTA were performed. Two patients had two repeat tests performed. There was good agreement between the tests. There was one occurrence of discordant testing in which the patient was classified as being responsive by LTA (10.4%) and having a low response by TEGPM (30.1%).\u003c/p\u003e \u003cp\u003eSeven (23%) of patients demonstrated non-response to prescribed aspirin therapy as defined by TEGPM and/or LTA on initial testing. Laboratory test results are detailed in Table \u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. There was no statistically significant difference between the median age of the two groups, but non-responders were more likely to be under 1 year. There were no statistically significant differences between the baseline characteristics and testing context between the two groups (out-patient vs. post-operative or post-procedural).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e\u0026ndash; Laboratory Test Results\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTesting points\u003c/p\u003e \u003cp\u003e- \u003cem\u003eTEG-PM\u003c/em\u003e\u003c/p\u003e \u003cp\u003e- \u003cem\u003eLTA\u003c/em\u003e\u003c/p\u003e \u003cp\u003e- \u003cem\u003eBoth\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;39\u003c/p\u003e \u003cp\u003e- \u003cem\u003e37 (95)\u003c/em\u003e\u003c/p\u003e \u003cp\u003e- \u003cem\u003e34 (87)\u003c/em\u003e\u003c/p\u003e \u003cp\u003e- \u003cem\u003e32 (82)\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNon-responsive on initial testing\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (23)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiscordant testing\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLTA (median) responsive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.45% (0.7\u0026ndash;20%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTEGPM (median) responsive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100% (64\u0026ndash;100%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLTA (median) non-responsive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25.45% (24.9\u0026ndash;40%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTEGPM (median) non-responsive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13.25% (0\u0026ndash;44%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003csup\u003e\u003cb\u003eValues are Median (minimum to maximum), n(%), unless otherwise stated, SD = standard deviation, TEG\u0026minus;PM = Thrombo\u0026minus;elastography with platelet mapping, LTA = light transmission platelet aggregometry\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e\u0026ndash; Comparison of Characteristics of Responders and Non-responders\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNon-responders (n\u0026thinsp;=\u0026thinsp;7)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eResponders (n\u0026thinsp;=\u0026thinsp;23)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge* (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.75 (0.2\u0026ndash;13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (2\u0026ndash;18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.076\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnder 1 year\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.048\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWeight* (kg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (4\u0026ndash;50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27 (6\u0026ndash;69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.133\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNormalised dose (mg/kg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.29 (1.5\u0026ndash;5.35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.63 (0.54\u0026ndash;4.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.066\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePost-op\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.99\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePost-procedure\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.29\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003e\u003csup\u003e\u003cb\u003eValues are Median (minimum to maximum), n(%), unless otherwise stated. * parameters assessed using Mann Whitney U Test, remaining parameters assessed used Figher\u0026rsquo;s Exact test.\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eOutcomes of patients demonstrating aspirin non-response\u003c/h2\u003e \u003cp\u003eThe baseline characteristics and outcomes of the 7 patients demonstrating inadequate response to aspirin (non-response) on initial testing are outlined in Table \u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e. Where there was an initial abnormal test result, patients were invited to return for repeat confirmatory testing. In case 5, repeat testing was not performed, and aspirin dose was increased at the discretion of the attending physician.\u003c/p\u003e \u003cp\u003eSix patients had repeat testing performed, and in 5 of the 6 cases, the repeat test was normal. In case 1, non-adherence with the prescribed dose was identified. In case 2, the initial sample was taken in-hospital in the post-operative setting. Repeat testing beyond the post operative period demonstrated normal response. In case 3 no cause was identified. In case 4, test timing may be implicated with the previous dose had been taken 24 hours before the sample. In case 7 there was discordant testing which was no longer apparent on repeat (described above). In case 6, aspirin non-response was identified on an appropriate dose on sequential testing that resolved on dose increase.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e\u0026ndash; Outcomes of patients demonstrating aspirin non-response\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"11\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo.\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDiagnosis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eConduit/ Valve\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAge (yrs)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eWeight\u003c/p\u003e \u003cp\u003e(kg)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eDose\u003c/p\u003e \u003cp\u003e(mg)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eTEGPM (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eLTA (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eTest repeated\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eRepeat result\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003eOutcome\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePulmonary atresia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRV-PA Conduit\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e26.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eAdherence discussed\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePulmonary atresia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRV-PA Conduit\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e37.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003epending\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eAttributed to post-operative period\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePulmonary atresia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBJV in RV-PA Conduit\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eNo change\u003c/p\u003e \u003cp\u003eNo cause identified\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePulmonary stenosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBJV (pulmonary)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eDose timing\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTetralogy of Fallot\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBJV (pulmonary)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e24.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eno\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eDose increase\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTruncus Arteriosus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eRV-PA Conduit\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e18.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e44.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eResistant\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eDose increase.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eComplex TGA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBJV (tricuspid)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e30.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e10.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eyes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eResolution of discordant testing on repeat\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"11\" nameend=\"c11\" namest=\"c1\"\u003e \u003cp\u003e\u003csup\u003e\u003cb\u003eTEGPM = thromboelastography with platelet mapping, LTA = light transmission platelet aggregometry, RV\u0026minus;PA = Right ventricle to pulmonary artery, BJV = Bovine jugular venous valve, TGA = transposition of the great arteries\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"DISCUSSION","content":"\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eSummary\u003c/h2\u003e \u003cp\u003eIn this prospectively recruited observational series, this is the first time that the rate of aspirin non-responsiveness amongst patients with BJV systems and xenograft valved conduits has been reported. An initial rate of aspirin non-responsiveness of 23% was identified in this group. However, in 17% (n\u0026thinsp;=\u0026thinsp;5) of patients repeat confirmatory testing at a separate time point was normal, with non-adherence to the correct dose of aspirin confirmed in 3% (n\u0026thinsp;=\u0026thinsp;1). The true rate of aspirin non-responsiveness requiring dose increase in this group may be as low as 6.7%. In 10% (n\u0026thinsp;=\u0026thinsp;3), testing for aspirin response resulted in a therapeutic intervention consisting of dose increases in two cases and medication education in another. Non-responders were more likely to be under the age of 1 (29% vs 0%). Of the two non-responders under 1, one was in the post-operative period. Increased vigilance in this age group may be advised. Agreement between tests was strong, which if consideration was made to adoption of testing to routine practice would decrease phlebotomy requirements. Repeat testing is recommended for instances of discordance.\u003c/p\u003e \u003cp\u003ePrevious studies of paediatric patients with congenital heart disease have demonstrated rates of aspirin non-responsiveness between 10\u0026ndash;50% [\u003cspan additionalcitationids=\"CR20 CR21\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Some of the variation in reported rates may be attributable to the context in which testing was performed with previous literature largely focusing on the post-operative period, which appears to be a high-risk period for decreased response and often in those with single ventricle physiology. For example, rates of up to 80% have been identified, in the early post operative period in neonates and infants following first stage surgical palliation for single ventricle physiology [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Additionally, cardiopulmonary bypass appears to impact rates of aspirin non-responsiveness [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Inadequate response to aspirin in post-operative paediatric patients with CHD, has been demonstrated to be associated with higher mortality from thrombotic events [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Furthermore, testing for aspirin response in the post-operative period and intervening with dose increases has been shown to lower rates of thrombotic events [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. However, in the context of BJV systems and xenograft valved conduits, the role that aspirin non-responsiveness may play in valve longevity and risk of IE has not been demonstrated. This is the first study to explore the rate of aspirin non- responsiveness in this context, with further studies being necessary to explore the link between inadequate response and adverse outcomes.\u003c/p\u003e \u003cp\u003eA strength of this study is that confirmatory testing was requested prior to therapeutic changes and interestingly a proportion of patients initially deemed non-responsive were responsive on repeat. In adult series, pharmacokinetic resistance is frequently identified in such cases. Pharmacokinetic resistance signifies low plasma levels of aspirin despite adequate intake. Frequently prescribed enteric-coated preparations can have significant effects on bio-availability and are the norm unless specified by the prescribing physician [\u003cspan additionalcitationids=\"CR26 CR27\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Concurrent use of NSAIDs, and proton-pump inhibitors can also affect bioavailability [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Adherence with medication has been implicated in adult studies on aspirin resistance [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e], but adherence may be underestimated in the paediatric population [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Pharmacodynamic resistance in which there is adequate bioavailability of aspirin but no inhibition in-vitro appears to be rare, especially that which cannot be overcome by dose increase [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eThis is a small, single-centre observational study, without control group for comparison. This study was not powered to assess whether aspirin non-responsiveness was associated with adverse outcomes in this group of patients. Not assessed by this study is the link between genetic polymorphisms and inadequate response to aspirin. Gene polymorphisms in dual antiplatelet therapy may be associated with the presence of leaflet thickening after transcatheter aortic valve replacement [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e], but this has not been demonstrated post TPVR.\u003c/p\u003e \u003cp\u003eNotable in this series is the rate of prior IE of 13% indicating that this is certainly a high-risk group. However, this is not indicative of IE within the study period and inferences between aspirin response and IE could not be drawn.\u003c/p\u003e \u003cp\u003eThe variable response to aspirin in some patients over time is not fully understood. False positive test results need to be considered. However, in an effort to mitigate against this, all patients were analysed by employing two assays where possible. A surrogate agonist AA was substituted into the TEG assay to confirm TEG results. All analysis was repeated on the same samples using the initial two assays to confirm results. Therefore, fluctuations in response may be due to non-adherence or pharmacokinetics (typically attributed to enteric coated preparations or drug-drug interactions). The implications of fluctuating response to aspirin are not known.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThe rate of aspirin non-responsiveness amongst paediatric patients with bovine jugular venous valve systems or xenograft valved conduits was 24% and testing for aspirin response should be considered in these patients. However, only 6.7% of patients required dose increases. The authors recommend reviewing aspirin dose regularly and up-titrating dose for weight, with consideration for responsiveness testing with dose increases particularly under the age of 1 year. Increased vigilance for non-response in the post operative period has been previously shown to reduce thrombotic events [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Where non-response is identified, confirmation of adherence and additional medications should be reviewed. The authors advocate for the prescription of non-enteric coated preparations. A testing algorithm has been proposed (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eWhether aspirin possesses a protective effect against the development of IE and valve failure in these patients remains to be fully elucidated. Echoing the call from previous literature, there is a need for clear guidance on the optimal anti-platelet regimen in this patient cohort [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank the patients and their families who participated in this study. Special thanks to Jennie Ryan, Molly O’Toole, Rachel Birmingham, Jackie Campion, Nicky Smith, and Ciara Sheridan of the Cardiac Day Unit at Children’s Health Ireland for all their help with study. In addition, we would like to thank Dr. Michaeala Pentony for her help with study recruitment.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors contributed to the manuscript. Sean T. Kelleher and Irene E. Regan collated the data and wrote the first draft. Dermot Cox, Kathryn Shaw, Orla Franklin, Damien P. Kenny and Kevin P. Walsh edited the manuscript and made important amendments to the manuscript including extensive points of discussion. Colin J. McMahon devised the study, helped collate data, edited and submitted the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no relevant financial interests to disclose. Damien P. Kenny is a member of the editorial board of Pediatric Cardiology.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding support: \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by an institutional grant as part of a Clinical Research Fellowship for IER from the National Children’s Research Centre, Ireland.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Sharing Agreement:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData available on request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompliance with Ethical Standards:\u003c/strong\u003e\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eThe study protocol was approved by the Ethics department at Children’s Health Ireland (CHI) Crumlin Dublin Ireland (GEN/580/17).\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eThe study complied with the Declaration of Helsinki for medical research involving human subjects.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eInformed consent was obtained from patients or their parents (where appropriate) for study inclusion.\u003c/li\u003e\n \u003cli\u003eThere is no conflict of interest for any author. No author has a financial or personal relationship with people/organisations that could inappropriately influence his/her work.\u003c/li\u003e\n \u003cli\u003eThe STROBE Checklist for observational studies was adhered to when preparing the manuscript.\u0026nbsp;\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eHybiak J, Broniarek I, Kiryczyński G, Los LD, Rosik J, Machaj F et al (2020) Aspirin and its pleiotropic application. Eur J Pharmacol 866:172762\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHankey GJ, Eikelboom JW (2006) Aspirin resistance. Lancet 367(9510):606\u0026ndash;617\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIchikawa Y (1992) A new RV-PA conduit with a natural valve made of bovine jugular vein. Asaio j 38(3):M266\u0026ndash;M270\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eR\u0026uuml;ffer A, Wittmann J, Potapov S, Purbojo A, Gl\u0026ouml;ckler M, Koch AM et al (2012) Mid-term experience with the Hancock porcine-valved Dacron conduit for right ventricular outflow tract reconstruction. Eur J Cardiothorac Surg 42(6):988\u0026ndash;995\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrown JW, Ruzmetov M, Rodefeld MD, Vijay P, Darragh RK (2006) Valved bovine jugular vein conduits for right ventricular outflow tract reconstruction in children: an attractive alternative to pulmonary homograft. Ann Thorac Surg 82(3):909\u0026ndash;916\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eArmstrong AK, Balzer DT, Cabalka AK, Gray RG, Javois AJ, Moore JW et al (2014) One-year follow-up of the Melody transcatheter pulmonary valve multicenter post-approval study. JACC Cardiovasc Interv 7(11):1254\u0026ndash;1262\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKenny D, Rhodes JF, Fleming GA, Kar S, Zahn EM, Vincent J et al (2018) 3-Year Outcomes of the Edwards SAPIEN Transcatheter Heart Valve for Conduit Failure in the Pulmonary Position From the COMPASSION Multicenter Clinical Trial. JACC Cardiovasc Interv 11(19):1920\u0026ndash;1929\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePromphan W, Prachasilchai P, Siripornpitak S, Qureshi SA, Layangool T (2016) Percutaneous pulmonary valve implantation with the Venus P-valve: clinical experience and early results. Cardiol Young 26(4):698\u0026ndash;710\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim RW (2018) Melody Mitral Valve Replacement Is No Longer an Experimental Procedure. Circ Cardiovasc Interv 11(11):e007455\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGodart F, Baruteau AE, Petit J, Riou JY, Sassolas F, Lusson JR et al (2014) Transcatheter tricuspid valve implantation: a multicentre French study. Arch Cardiovasc Dis 107(11):583\u0026ndash;591\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcElhinney DB, Zhang Y, Levi DS, Georgiev S, Biernacka EK, Goldstein BH et al (2022) Reintervention and Survival After Transcatheter Pulmonary Valve Replacement. J Am Coll Cardiol 79(1):18\u0026ndash;32\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSharma A, Cote AT, Hosking MCK, Harris KC (2017) A Systematic Review of Infective Endocarditis in Patients With Bovine Jugular Vein Valves Compared With Other Valve Types. JACC Cardiovasc Interv 10(14):1449\u0026ndash;1458\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcElhinney DB, Zhang Y, Aboulhosn JA, Morray BH, Biernacka EK, Qureshi AM et al (2021) Multicenter Study of Endocarditis After Transcatheter Pulmonary Valve Replacement. J Am Coll Cardiol 78(6):575\u0026ndash;589\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShibbani K, Garg R, Zahn EM, McLennan D (2021) Aspirin Use and Transcatheter Pulmonary Valve Replacement, the Need for Consistency. Pediatr Cardiol 42(7):1640\u0026ndash;1646\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGoldstein BH, Bergersen L, Armstrong AK, Boe BA, El-Said H, Porras D et al (2020) Adverse Events, Radiation Exposure, and Reinterventions Following Transcatheter Pulmonary Valve Replacement. J Am Coll Cardiol 75(4):363\u0026ndash;376\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJewgenow P, Schneider H, B\u0026ouml;kenkamp R, H\u0026ouml;rer J, Cleuziou J, Foth R et al (2019) Subclinical thrombus formation in bioprosthetic pulmonary valve conduits. Int J Cardiol 281:113\u0026ndash;118\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMalekzadeh-Milani S, Ladouceur M, Patel M, Boughenou FM, Iserin L, Bonnet D et al (2015) Incidence and predictors of Melody\u0026reg; valve endocarditis: a prospective study. Arch Cardiovasc Dis 108(2):97\u0026ndash;106\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJ\u0026oslash;rgen B, Nikolai N, Lasse Holtan P, Ingunn T, Kathrin B (2021) Adjusting the dose in paediatric care: dispersing four different aspirin tablets and taking a proportion. Eur J Hosp Pharm 28(2):76\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEmani S, Zurakowski D, Mulone M, DiNardo JA, Trenor CC, Emani SM (2017) Platelet testing to guide aspirin dose adjustment in pediatric patients after cardiac surgery. J Thorac Cardiovasc Surg 154(5):1723\u0026ndash;1730\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKoh W, Rodts M, Nebbia A, Sawyer J, Henry B, Cooper DS (2022) Aspirin resistance in infants with shunt-dependent congenital heart disease. Cardiol Young 32(5):705\u0026ndash;710\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEmani S, Trainor B, Zurakowski D, Baird CW, Fynn-Thompson FE, Pigula FA et al (2014) Aspirin unresponsiveness predicts thrombosis in high-risk pediatric patients after cardiac surgery. J Thorac Cardiovasc Surg 148(3):810\u0026ndash;814 discussion 4\u0026ndash;6\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePatregnani J, Klugman D, Zurakowski D, Sinha P, Freishtat R, Berger J et al (2016) High on Aspirin Platelet Reactivity in Pediatric Patients Undergoing the Fontan Procedure. Circulation 134(17):1303\u0026ndash;1305\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMir A, Frank S, Journeycake J, Wolovitis J, Guleserian K, Heistein L et al (2015) Aspirin Resistance in Single-Ventricle Physiology: Aspirin Prophylaxis Is Not Adequate to Inhibit Platelets in the Immediate Postoperative Period. Ann Thorac Surg 99(6):2158\u0026ndash;2164\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZimmermann N, Kurt M, Wenk A, Winter J, Gams E, Hohlfeld T (2005) Is cardiopulmonary bypass a reason for aspirin resistance after coronary artery bypass grafting? Eur J Cardiothorac Surg 27(4):606\u0026ndash;610\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCox D, Maree AO, Dooley M, Conroy R, Byrne MF, Fitzgerald DJ (2006) Effect of enteric coating on antiplatelet activity of low-dose aspirin in healthy volunteers. Stroke 37(8):2153\u0026ndash;2158\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMaree AO, Curtin RJ, Dooley M, Conroy RM, Crean P, Cox D et al (2005) Platelet response to low-dose enteric-coated aspirin in patients with stable cardiovascular disease. J Am Coll Cardiol 46(7):1258\u0026ndash;1263\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePeace A, McCall M, Tedesco T, Kenny D, Conroy RM, Foley D et al (2010) The role of weight and enteric coating on aspirin response in cardiovascular patients. J Thromb Haemost 8(10):2323\u0026ndash;2325\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcCall M, Peace A, Tedesco AF, Foley D, Conroy RM, Cox D (2020) Weight as an assay-independent predictor of poor response to enteric aspirin in cardiovascular patients. Platelets 31(4):530\u0026ndash;535\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShantsila E, Lip GYH (2008) Aspirin resistance' or treatment non-compliance: Which is to blame for cardiovascular complications? J Translational Med 6(1):47\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKardas P, Dabrowa M, Witkowski K (2021) Adherence to treatment in paediatric patients \u0026ndash; results of the nationwide survey in Poland. BMC Pediatr 21(1):16\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXiong TY, Liao YB, Feng Y, Zhao MY, Zhao ZG, Li YJ et al (2018) Gene polymorphisms in dual antiplatelet therapy and the presence of hypo-attenuated leaflet thickening after transcatheter aortic valve replacement. J Thromb Thrombolysis 45(3):463\u0026ndash;465\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"pediatric-cardiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pedc","sideBox":"Learn more about [Pediatric Cardiology](http://link.springer.com/journal/246)","snPcode":"246","submissionUrl":"https://submission.nature.com/new-submission/246/3","title":"Pediatric Cardiology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Aspirin, conduit, jugular venous valve, platelet, resistance, thrombosis","lastPublishedDoi":"10.21203/rs.3.rs-3244339/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3244339/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective: \u003c/strong\u003eThe aim of this study was to determine the rate of aspirin responsiveness in a cohort of paediatric patients with in-situ xenograft valved right ventricle to pulmonary artery (RV-PA) conduits and/or bovine jugular venous valves (BJV). Aspirin is routinely prescribed to these patients. Optimising anti-platelet therapy could promote valve longevity and reduce the risk of infective endocarditis in this at-risk group.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMaterials and Methods: \u003c/strong\u003eThis was a prospective, observational study. Patients were recruited from both ward and outpatient settings. Patients were eligible if under 18 years and taking aspirin. Non-response to aspirin was defined as \u0026gt;20% platelet aggregation using light-transmission platelet aggregometry (LTA) and \u0026lt;50% platelet inhibition by thromboelastography with platelet mapping (TEGPM). Participants were invited to provide a confirmatory sample in cases of aspirin resistance and dose adjustments were made.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults: \u003c/strong\u003eThirty patients participated. Median age was 9 years (2 months – 18 years). The majority (93%) had complex right ventricular outflow tract pathology. 13 (43%) had an RV-PA conduit, 24 (80%) had a BJV, with valve situated in conduit in 7 (23%) cases. Rate of aspirin non-response on initial testing was 23% (n=7/30) with median LTA 25.45% (24.9-40%) and TEG 13.25% (0-44%) in non-responders. Non-responders were more likely to be under 1 year. Two patients required dose increases and one patient non-adherence to dose was identified. In 4 patients repeat testing revealed normal results.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions \u003c/strong\u003eThe rate of aspirin non-response on laboratory testing in this cohort of patients was 23% and resulted in therapeutic intervention in 10%.\u003c/p\u003e","manuscriptTitle":"Aspirin Responsiveness in a Cohort of Paediatric Patients With Bovine Jugular Venous Valves and Right Ventricle to Pulmonary Artery Conduits","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-08-16 13:53:07","doi":"10.21203/rs.3.rs-3244339/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2023-12-18T22:34:44+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2023-09-28T19:36:32+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2023-09-24T23:15:01+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"ab524b2c-188d-4911-abf7-a1d1910a04b6","date":"2023-09-22T00:39:51+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"0ae8b1c6-9b79-41de-b087-6da33973e5cb","date":"2023-09-19T22:57:21+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2023-09-18T17:27:46+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2023-08-09T12:59:47+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2023-08-09T12:59:47+00:00","index":"","fulltext":""},{"type":"submitted","content":"Pediatric Cardiology","date":"2023-08-08T06:53:17+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"pediatric-cardiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"pedc","sideBox":"Learn more about [Pediatric Cardiology](http://link.springer.com/journal/246)","snPcode":"246","submissionUrl":"https://submission.nature.com/new-submission/246/3","title":"Pediatric Cardiology","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"d3fd5eb1-5a85-4c8d-8db9-0365651e6b60","owner":[],"postedDate":"August 16th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-03-18T15:09:01+00:00","versionOfRecord":{"articleIdentity":"rs-3244339","link":"https://doi.org/10.1007/s00246-024-03449-1","journal":{"identity":"pediatric-cardiology","isVorOnly":false,"title":"Pediatric Cardiology"},"publishedOn":"2024-03-15 15:01:13","publishedOnDateReadable":"March 15th, 2024"},"versionCreatedAt":"2023-08-16 13:53:07","video":"","vorDoi":"10.1007/s00246-024-03449-1","vorDoiUrl":"https://doi.org/10.1007/s00246-024-03449-1","workflowStages":[]},"version":"v1","identity":"rs-3244339","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3244339","identity":"rs-3244339","version":["v1"]},"buildId":"_2-kVJe1T_tPrBINL-cwx","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}