INTRODUCTION:Inhibitor development against factor VIII (FVIII) is the most common complication of hemophilia A replacement therapy. One of the variables considered to influence inhibitor development is the ABO blood group. Patients with blood group O have, on average, a 30%-40% lower endogenous von Willebrand factor (VWF) concentration. It has been postulated that VWF levels influence inhibitor development. The objective of this study was to investigate the inhibitor risk in patients with severe hemophilia A comparing those with blood group O with those with non-O blood groups. METHODS:The study population consisted of children with severe hemophilia A, born between 2000 and 2020, who reached 50 FVIII exposure days in the PedNet registry. Inhibitors were considered to be clinically relevant when at least two consecutive measurements were tested positive. RESULTS:Routine testing of blood groups varied between centres: Out of 1172 patients with severe hemophilia A, blood group status was known in 759 patients (65.8%). The relative risk of inhibitor development for blood group O in comparison to non-O was 1.04 (95% CI: 0.7-1.7). CONCLUSION:In the PedNet cohort, blood group O did not increase the risk of inhibitors in previously untreated children with severe hemophilia A. TRIAL REGISTRATION:PedNet Registry; clinicaltrials.gov identifier: NCT02979119.

Background: Inhibitor eradication to restore factor (F)VIII efficacy is the treatment goal for persons with severe hemophilia A (HA) and inhibitors. Immune tolerance induction (ITI) is demanding and successful in about 70% of people. Until now, it has remained difficult to quantify the probability of ITI success or failure, complicating the decision to initiate or not initiate ITI. Estimating the individual chance of ITI success allows clinicians, patients, and their families to support shared decision-making. Objectives: We aimed to identify clinical predictors of ITI success and to develop a clinical prediction model to estimate the chance of successful ITI in persons with severe HA. Methods: This multicenter study included persons with severe HA who received ITI. Clinical data were collected. Successful ITI was defined by a negative inhibitor titer and an adequate response to FVIII concentrates. A multivariable logistic regression model was developed. Model performance and internal validation were performed. Results: Of 206 participants with a median age of 19.8 months (IQR, 12.1-38.8) at ITI start, 148 (71.8%) achieved ITI success. Our clinical prediction model included 4 predictors of ITI success: cumulative number of FVIII exposure days at inhibitor development, peak inhibitor titer, ethnicity, and F8 mutation type. The C statistic was 0.801 (95% CI, 0.70-0.87). Conclusion: In our study, including 206 people with severe HA and inhibitors, we developed a clinical prediction model to estimate the chance of successful ITI. After future external validation, this clinical prediction model may be useful for informing clinicians and families.

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Background: Clotting factor concentrates have been the mainstay of severe hemophilia treatment over the last 50 years. Differences in risk of neutralizing antibody (inhibitor) formation according to concentrate used remain clinically relevant.Objectives: To assess inhibitor development according to type of clotting factor concentrate in previously untreated patients (PUPs) with severe hemophilia A and B.Methods: The European Haemophilia Safety Surveillance (EUHASS) and Canadian Bleeding Disorders Registry (CBDR) have been monitoring adverse events overall and according to concentrate for 11 and 8 years, respectively. Inhibitors were reported quarterly, and PUPs completed 50 exposure days without inhibitor development annually. Cumulative inhibitor incidences and 95% confidence intervals (CIs) were compared without adjustment for other risk factors.Results: Fifty-six European and 23 Canadian centers reported inhibitor development in 312 of 1219 (26%; CI, 23%-28%) PUPs with severe hemophilia A and 14 of 173 (8%; CI, 5%-13%) PUPs with severe hemophilia B. Inhibitor development was lower on plasma -derived factor (F)VIII (pdFVIII, 20%; CI, 14%-26%) than on standard half-life recom-binant FVIII (SHL-rFVIII, 27%; CI, 24%-30% and odds ratio, 0.67; CI, 0.45%-0.98%; P = .04). Extended half-life recombinant FVIII (EHL-rFVIII, 22%; CI, 12%-36%) showed an intermediate inhibitor rate, while inhibitor rates for Advate (26%; CI, 22%-31%) and Kogenate/Helixate (30%; CI, 24%-36%) overlapped. For other SHL-rFVIII concentrates, inhibitor rates varied from 3% to 43%. Inhibitor development was similar for pdFIX (11%; CI, 3%-25%), SHL-rFIX (8%; CI, 3%-15%), and EHL-rFIX (7%; CI, 1%-22%).Conclusion: While confirming expected rates of inhibitors in PUPs, inhibitor develop-ment was lower in pdFVIII than in SHL-rFVIII. Preliminary data suggest variation in inhibitor development among different SHL-rFVIII and EHL-rFVIII concentrates.

HaemophiliaVolume 29, Issue 1 p. 348-351 LETTER TO THE EDITOR Switching to emicizumab: A prospective surveillance study in haemophilia A subjects with inhibitors Evemie Dubé, Evemie Dubé CHU Sainte-Justine, Montréal, CanadaSearch for more papers by this authorClémence Merlen, Clémence Merlen CHU Sainte-Justine, Montréal, CanadaSearch for more papers by this authorArnaud Bonnefoy, Arnaud Bonnefoy CHU Sainte-Justine, Montréal, CanadaSearch for more papers by this authorJosie Pilon, Josie Pilon CHU Sainte-Justine, Montréal, CanadaSearch for more papers by this authorNichan Zourikian, Nichan Zourikian CHU Sainte-Justine, Montréal, CanadaSearch for more papers by this authorJulie Gauthier, Julie Gauthier CHU Sainte-Justine, Montréal, CanadaSearch for more papers by this authorJean St-Louis, Jean St-Louis orcid.org/0000-0003-1183-533X CHU Sainte-Justine, Montréal, Canada Hôpital Maisonneuve-Rosemont, Montréal, CanadaSearch for more papers by this authorGeorges-Étienne Rivard, Corresponding Author Georges-Étienne Rivard [email protected] CHU Sainte-Justine, Montréal, Canada Correspondence Georges-Etienne Rivard, CHU Sainte-Justine, University of Montreal, 3175, chemin de la Côte-Ste-Catherine, Montreal, Quebec H3T 1C5, Canada. Email: [email protected]Search for more papers by this author Evemie Dubé, Evemie Dubé CHU Sainte-Justine, Montréal, CanadaSearch for more papers by this authorClémence Merlen, Clémence Merlen CHU Sainte-Justine, Montréal, CanadaSearch for more papers by this authorArnaud Bonnefoy, Arnaud Bonnefoy CHU Sainte-Justine, Montréal, CanadaSearch for more papers by this authorJosie Pilon, Josie Pilon CHU Sainte-Justine, Montréal, CanadaSearch for more papers by this authorNichan Zourikian, Nichan Zourikian CHU Sainte-Justine, Montréal, CanadaSearch for more papers by this authorJulie Gauthier, Julie Gauthier CHU Sainte-Justine, Montréal, CanadaSearch for more papers by this authorJean St-Louis, Jean St-Louis orcid.org/0000-0003-1183-533X CHU Sainte-Justine, Montréal, Canada Hôpital Maisonneuve-Rosemont, Montréal, CanadaSearch for more papers by this authorGeorges-Étienne Rivard, Corresponding Author Georges-Étienne Rivard [email protected] CHU Sainte-Justine, Montréal, Canada Correspondence Georges-Etienne Rivard, CHU Sainte-Justine, University of Montreal, 3175, chemin de la Côte-Ste-Catherine, Montreal, Quebec H3T 1C5, Canada. Email: [email protected]Search for more papers by this author First published: 31 October 2022 https://doi.org/10.1111/hae.14685 Evemie Dubé and Clémence Merlen contributed equally to this study. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Volume29, Issue1January 2023Pages 348-351 RelatedInformation

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Quebec platelet disorder (QPD) is an autosomal-dominant bleeding disorder with a platelet-dependent gain-of-function defect in fibrinolysis.(1)QPD results in a 100-fold increase of urokinase plasminogen activator in megakaryocytes and platelets, which accelerates clot lysis and increases bleeding.(2) The estimated prevalence is 1 per 655,000 across Canada, with cases emerging in other countries as well.(1) Fibrinolytic inhibitors are the only effective treatment.(3) Concurrent anticoagulant and tranexamic acid (TXA) have been used for short durations, but long-term safety is unknown. We describe a multi-disciplinary approach to the management of a patient with QPD, atrial fibrillation (AF) and cardioembolic strokes from a left atrial appendage (LAA) thrombus.

BackgroundHereditary angioedema (HAE) is a rare autosomal dominant disease; the most well understood forms concern the haplodeficiency of C1 esterase inhibitor (C1INH) and a gain of function mutation of factor XII (FXII). The acute forms of these conditions are mediated by an excessive bradykinin (BK) formation by plasma kallikrein.MethodsA validated LC-MS/MS platform of picomolar sensitivity developed for the analysis of eleven bradykinin-related peptides was applied to the plasma of HAE-C1INH and HAE-FXII sampled during remission.ResultsIn HAE-C1INH plasma, the concentrations of the relatively stable BK1−5 fragment (mean ± S.E.M.: 12.0 ± 4.2 pmol/L), of BK2−9 (0.7 ± 0.2 pmol/L) and of the sums of BK and its tested fragments (18.0 ± 6.4 pmol/L) are significantly greater than those recorded in the plasma of healthy volunteers (1.9 ± 0.6, 0.03 ± 0.03 and 4.3 ± 0.8 pmol/L, respectively), consistent with the previous evidence of permanent plasma kallikrein activity in this disease. Kinin levels in the plasma of HAE-FXII patients did not differ from controls, suggesting that triggering factors for contact system activation are not active during remission.ConclusionBK1−5, BK2−9 and the sum of BK and its fragments determined by the sensitive LC-MS/MS technique are proposed as potential biomarkers of HAE-C1INH in remission while this was not applicable to HAE-FXII patients.

In 2018, following a provincial tender process, most persons with haemophilia A (PWHA) in the province of Quebec (Canada) were switched to the two recombinant B-domain-truncated factor VIII (FVIII) known as Zonovate® (NovoNordisk, Mississauga, Canada) and Nuwiq® (Octapharma AG, Lachen, Switzerland) with an estimated market distribution of respectively 53% and 47%. Even if HA management has greatly improved over the last decades with the availability of several FVIII concentrates and bypassing agents, inhibitors remain the most serious complication of HA treatment and switching FVIII concentrate has been reported to be associated with a low but not insignificant risk of FVIII inhibitor development. This adverse event is associated with a higher risk of bleeding complications and a reduced quality of life.1 Inhibitors usually occur within the first 50 exposure days to FVIII replacement therapy in severe HA,2 but the risk is still present throughout life.3 We conducted a surveillance study to evaluate, as a primary outcome, the incidence of anti-FVIII antibodies development and, as secondary outcomes, FVIII recovery, FVIII usage and annualized bleeding rates (ABR). All assays were centralized at the CHU Sainte-Justine Hemostasis Laboratory. The study was approved by ethics committees of all participating centers. A total of 47 children and 94 adults were enrolled from April 2018 to December 2019 and completed, when feasible, 3 visits 0, 6 and 12 months post-switch (respectively visit 1, 2 and 3). Each participant gave informed written consent. One male subject was excluded upon study entry due to the presence of an inhibitor (≥0.6BU/mL). Another male subject was withdrawn from further analyses due to insufficient data and absence of blood samples at all visits. Mean age of the remaining cohort of 139 subjects was 26 years (range 3 to 58 years). Most subjects had severe HA (FVIII<0.01IU/mL, 90.6%), had a high-risk F8mutation (60.4%) and hadmore than 150 exposures days (ED) of replacement factor (92.1%). Only 3 subjects that switched to Zonovate®had less than 50ED,more precisely between 11 and50ED. Upon study entry, most subjects were on prophylaxis (95%) with doses ranging from5.4 to 46 IU/kg every day to once perweek. Subjectswere either on Xyntha® (90.7%), Advate® (7.2%) or Humate-P® (2.1%). Respectively 67 and 72 subjects switched to Nuwiq® (36 children and 31 adults) and Zonovate® (13 children and 59 adults). The choice of the product was made on mutual agreement between patients and treaters, with human cell-derived Nuwiq® favored for children who were previously treated with Humate-P. Among the 74 subjects who completed visit 3, 8 changed their regimen (dosing and/or frequency) between visit 1 and visit 3. Nine percent of participants had a known personal history of inhibitors and were distributed among the different groups (3 children and 2 adults switching to Nuwiq®; 6 children and 2 adults switching to Zonovate®). All these participants were inhibitor-free upon study entry. As a first step to evaluate the presence of inhibitors, FVIII recovery (IU/dL/IU/kg, measured by one-stage clotting assay) was assessed for 111, 63 and 55 subjects respectively at visit 1, 2 and 3. FVIII activity lower than 1% was considered equal to 0 to calculate FVIII recovery (defined as the observed FVIII increase per unit of FVIII infused per kg). Analyses were not possible for 22, 6 and 18 participants respectively at visit 1, 2 and 3 due to logistic reasons (sampling not possible at designated timepoint or inadequate sample). Six subjects were also withdrawn from further analyses for FVIII recovery, ABRs and FVIII usage: the only female subject and five male subjects (three had multiple product switches during study time and two were still mainly using Xyntha® at the end of the study due to their reluctance to switch). Even if slight differenceswerenoted formeanFVIII recoverymeasured by one-stage clotting assay at visit 1 between children and adults (all products-combined; p = 0.0003; 1.95, 1.76, 1.8 respectively at visit 1, 2, 3 for children; 2.61, 2.40, 2.40 respectively at visit 1, 2, 3 for adults) aswell as betweenNuwiq®andZonovate® (p=0.0042; 2.09, 1.74, 1.9 respectively at visit 1, 2, 3 for Nuwiq®; 2.65, 2.38, 2.38 respectively at visit 1, 2, 3 for Zonovate®), all values were still comparable to previous reports,4–7 considering that 49.6% of our subjects were obese (20.1%) or overweight (29.5%)8,9 and that 73% of the children in our cohort were switched to Nuwiq®.7 As previously observed in clinical trials for Nuwiq® and Zonovate® in previously treated PWHA,10–13 no inhibitors were detected upon study entry by Nijmegen-modified Bethesda (NBA) assay or enzyme-linked immunosorbent assay (ELISA; used as a complementary approach to detect both neutralizing and non-neutralizing antibodies) even in the 3 subjects with less than 50 ED. Indeed, in these clinical trials, inhibitors were only detected in subjects with less than 25 EDs and high-risk F8 mutations.13,14 Two subjects were not tested upon study entry due to logistic reasons (insufficient or inadequate blood samples), but these two subjects had no personal history of inhibitors and had tested negative by NBA less than two months prior to study entry. On the 71 and 74 subjects that respectively completed visit 2 and 3, all tested negative by NBA and ELISA. Factor VIII usage (IU/kg/year) and annualized bleeding rates were respectively evaluated for 110 (42 children and 68 adults) and 107 subjects (41 children and 66 adults) over a period of 12±2months before and after the switch (Tables 1 and 2). FVIII usage and ABRs in

Abstract Background Thrombotic microangiopathies (TMA) are serious medical conditions requiring a prompt diagnosis to adapt treatment. The determination of ADAMTS-13 activity enables discriminating thrombotic thrombocytopenic purpura (TTP) from other forms of TMA. The purpose of this study was to provide an estimate of the incidence of TTP and TMA in the Canadian Quebec province using data collected from a laboratory centralizing ADAMTS-13 testing for the whole province. Results From 2012 to 2019, 846 patients were evaluated for plasma ADAMTS-13 activity due to a suspicion of TMA. TTP was identified in 147 patients. Of these, 118 patients with a median age of 51.5 years and a male–female ratio of 1:1.4 had their first episode of TTP during the study period. The number of ADAMTS-13 tests performed and the number of patients with suspected TMA increased annually by 19% and 21% respectively. While the incidence of non-TTP TMA increased annually, that for TTP remained unchanged. This averaged 10.2 (95% CI 5.9–14.4) per million persons per year for suspected non-TTP TMA and 1.8 (95% CI 1.3–2.4) for confirmed TTP. The incidence rate of TMA other than TTP was higher in the age group 70–79 years (21.8; 95% CI 5.4–38.1) for females and in the age group 80–89 years (24.4; 95% CI 7.2–41.7) for males compared to other age groups. The incidence rate of TTP was higher in the age group 40–49 years (4.0; 95% CI 2.0–5.9) for women and in the age group 60–69 years (3.4; 95% CI 1.1–5.6) for men compared to other age groups. Conclusion The analysis of centralized data measuring ADAMTS-13 activity allowed us to adequately establish the incidence rate and demographic characteristics of TMA, particularly TTP, in Quebec. TTP incidence remained stable while suspected non-TTP TMA steadily increased from 2012 to 2019.

Aim: Gaucher disease (GD) is caused by a deficiency of the lysosomal enzyme acid β-glucocerebrosidase. Recent metabolomic studies highlighted several new metabolites increased in the plasma of GD patients. We aimed to develop and validate a UPLC-MS/MS method allowing a relative quantitation of lyso-Gb1 and lyso-Gb1 analogs -28, -12, -2, +14, +16 and +18 Da in addition to sphingosylphosphorylcholine, N-palmitoyl-O-phosphocholine to study potential correlations with clinical manifestations. Methodology & results: Following solid-phase extraction, plasma samples were evaporated and resuspended in 100 μl of resuspension solution. Three microliter is injected into the UPLC-MS/MS for analysis. Conclusion: All biomarkers studied were increased in GD patients. Significant correlations were observed between specific analogs and hematological, and visceral complications, as well as overall disease severity.

BACKGROUND: The systemic capillary leak syndrome (SCLS), also known as Clarkson disease, is a very rare condition characterized by recurrent life-threatening episodes of vascular hyperpermeability in the presence of a monoclonal gammop-athy. Extended intravenous immunoglobulin (IVIG) treatment is associated with fewer recurrences and improved survival, but the optimal treatment dosage and duration remain unknown.OBJECTIVE: We aim to evaluate the safety of IVIG tapering and withdrawal in patients with SCLS. METHODS: We conducted a retrospective multicenter study including all adult patients with monoclonal gammopathy-associated SCLS from the EureClark registry who received at least 1 course of IVIG. The primary end point was overall sur-vival according to IVIG withdrawal.RESULTS: Fifty-nine patients of mean - SD age 51 - 13 years were included. Overall cumulative probabilities of 2-, 5-, 10-and 15-year survival were 100%, 85%, 72%, 44%, respectively. The IVIG was withdrawn at least once in 18 patients (31%; W+ group) and never in 41 patients (69%; W-group). Cumulative probabilities of 10-year survival in W+ versus W-groups were 50% and 83% (log rank test, P = .02), respectively. Relapse rate and the median number of relapses in the W+ versus the W-groups were 72% versus 58% (P = 0.3) and 2.5 (0.3-4) versus 1 (0-2) (P = .03), respectively. The IVIG tapering was not sta-tistically associated with increased person-year incidence of at-tacks using a mixed linear model.CONCLUSIONS: The IVIG withdrawal was associated with increased mortality and higher rate of recurrence in SCLS patients. The IVIG tapering might be cautiously considered in stable SCLS patients. (c) 2022 American Academy of Allergy, Asthma & Immunology (J Allergy Clin Immunol Pract 2022;10:2889-95)

Glanzmann thrombasthenia (GT) is a rare autosomal recessive disorder of fibrinogen-mediated platelet aggregation due to a quantitative or qualitative deficit of the αIIbβ3 integrin at the platelet surface membrane resulting from mutation(s) in ITGA2B and/or ITGB3. Patients tend to present in early childhood with easy bruising and mucocutaneous bleeding. The diagnostic process requires consideration of more common disorders of haemostasis and coagulation prior to confirming the disorder with platelet light transmission aggregation, flow cytometry of CD41 and CD61 expression, and/or exon sequencing of ITGA2B and ITGB3. Antifibrinolytic therapy, recombinant activated factor VII, and platelet transfusions are the mainstay of therapy, although the latter may trigger formation of anti-platelet antibodies in GT patients and inadvertent platelet-refractory disease. The management of these patients therefore remains complex, particularly in the context of trauma, labour and delivery, and perioperative care. Bone marrow transplantation remains the sole curative option, although the venue of gene therapy is being increasingly explored as a future alternative for definitive treatment of GT.

Background This study examined the structural outcomes for joints of boys with severe hemophilia A receiving frequency/dose-escalated primary prophylaxis using magnetic resonance imaging (MRI), and the importance of interval MRI changes. Methods Forty-six subjects (27 with interval studies) were evaluated by radiographs (X-rays) and mid- and end-of-study MRIs (using the International Prophylaxis Study Group scale), as part of the Canadian Hemophilia Prophylaxis Study. The primary outcome was the presence of MRI osteochondral findings. Results The median (range) time on study at the end-of-study MRI examination was 9.6 (4.8-16.0) years, during which 18 of 46 subjects (39%) had osteochondral changes in at least one joint. An interval change in MRI score of at least 1 point was observed in 44% of joints (43 ankles, 21 elbows, 4 knees); at least one joint showed this change in all 27 subjects. Self-reported interval hemarthrosis was associated with a higher likelihood of interval osteochondral change (odds ratio [OR], 1.49; 95% confidence interval [CI] = 1.08-2.06). Presence of synovial hypertrophy or hemosiderin on interval MRIs was associated with an OR of 4.71 (95% CI, 1.92-11.57) and 5.25 (95% CI, 2.05-13.40) of later osteochondral changes on MRI. Discussion MRI changes were seen in 39% of subjects. Interval index joint bleeding was associated with an increased risk of later MRI changes, and earlier soft-tissue changes were associated with subsequent osteochondral changes. [GRAPHICS]

Industrial hemp is increasingly grown and harvested for its cannabinoids of pharmaceutical interest. These compounds are generally obtained from plants harvested at maturity but not all cannabinoids are present or abundant during the last stage of hemp development. This study examined intraspecific cannabinoid variability during ontogenic development of hemp to identify growth stages and cultivars that optimize production of specific compounds. The cannabinoid content of twelve commercial industrial hemp (Cannabis sativa L. subsp. sativa) cultivars at three growth stages (i.e., flowering, grain filling and maturity) was determined by high performance liquid chromatography in an experimental field in Cocagne, New Brunswick, Canada. Most cannabinoids in acidic or neutral form were more abundant at maturity. However, cannabigerolic acid, a precursor to all acidic and neutral forms of cannabinoids mentioned in our study, was more abundant during the grain-filling stage. In contrast, cannabichromene was associated with the flowering stage and found in greater abundances in grain cultivars than in dual-purpose cultivars. The cultivar Katani exhibited higher concentrations of most cannabinoids while the cultivars Ferimon, Altair and Anka exhibited higher concentrations of cannabinoid acidic precursors. The current study could help optimize the targeted production of cannabinoids at specific growth stages and to identify the chemical phenotype of different hemp cultivars.

Introduction: Monitoring the anticoagulant effect of heparin is critical to prevent thrombosis and/or bleeding during cardiac surgery. This evaluation is usually performed by assessing the activated clotting time (ACT) with a POC device. Despite the relevance and widespread use of ACT, there are currently limited reference values to use as a target. Furthermore, compared to the adult population, infants have been described with a longer ACT, reinforcing the need to establish a separate reference interval for this segment of the population. Aim: The present work aims to propose reference intervals of ACT in pediatric patients. Methods: We collected data on 155 consecutive patients, ranging in age from 1 day to 18 years, undergoing cardiac surgery from 01-2019 to 01-2021 at Sainte-Justine hospital. Prior to surgery, patients were given UFH as a bolus of 3 mg/kg, and Hemochron Signature Elite ACT+ (Accriva Diagnostics, Inc.) was used to measure ACT before and promptly after heparin injection. Data were subsequently analyzed by using a parametric method. Lower and upper reference limits are the values at the 2.5 and 97.5 percentile, respectively. Results: The ACT before heparin injection followed a normal distribution with a lower reference limit at 85 seconds and an upper limit at 147 seconds compared to the range of 70-120 seconds proposed for the general population. Interestingly, the ACT after heparin bolus exhibited a non-gaussian distribution. Since neonates have been previously described with a greater heparin resistance compared to older infants; patients were separated into two age groups: patients < 1-month of age (Group A; n=31) and patients > 1-month (group B; n=124). Afterward, we performed a log transformation of the ACT values after heparin injection to approximate a Gaussian distribution, yielding mean ACT value of 392 seconds (limits 291-529 seconds) for Group A and 473 seconds (limits 314-996 seconds) for Group B (Welch test p value = 4.4 10 -6 ). No significant difference in ACT values prior to heparin bolus was found between the two groups. Conclusion: Overall, our results provide reference values of ACT measured using an Hemochron device, in a pediatric context, paving the way for improved patient care during cardiac surgery.