Anthony Chan - Academia.edu (original) (raw)

Papers by Anthony Chan

Kidney360, 2020

Background There are limited data at a population level on the burden, risk factors, and long-ter... more Background There are limited data at a population level on the burden, risk factors, and long-term outcomes of neonatal renal vein thrombosis (nRVT). We conducted a population-based cohort study to understand the epidemiology and outcomes of nRVT over a 25-year period in Ontario. Methods Using linked administrative health databases, all hospitalized neonates ≤28 days born in Ontario between 1992 and 2016 with nRVT were identified. The primary outcome was to calculate the incidence of nRVT and trend over time in Ontario. We also determined the risk factors associated with nRVT as well as the risk of long-term outcomes after nRVT, including CKD, ESKD, all-cause mortality, and hypertension (HTN) compared with the healthy neonatal population without nRVT. Results The annual incidence rate of nRVT was 2.6 per 100,000 live births (n=85). Presence of respiratory distress syndrome (OR, 8.01; 95% CI, 4.90 to 13.1), congenital heart disease (OR, 9.1; 95% CI, 5.05 to 16.4), central venous cath...

Pediatric exercise science, Jan 10, 2014

The objectives of this study were to (i) assess sedentary time and prevalence of screen-based sed... more The objectives of this study were to (i) assess sedentary time and prevalence of screen-based sedentary behaviours of children with a chronic disease and (ii) compare sedentary time and prevalence of screen-based sedentary behaviours to age- and sex-matched healthy controls. Sixty-five children (aged 6-18 years) with a chronic disease participated: survivors of a brain tumor, haemophilia, type 1 diabetes mellitus, juvenile idiopathic arthritis, cystic fibrosis and…

Thrombosis and Haemostasis

Introduction BAY 81–8973, a full-length recombinant factor VIII for hemophilia A treatment, has b... more Introduction BAY 81–8973, a full-length recombinant factor VIII for hemophilia A treatment, has been extensively evaluated in previously treated patients in the LEOPOLD (Long-Term Efficacy Open-Label Program in Severe Hemophilia A Disease) clinical trials. Aim To assess BAY 81–8973 efficacy and safety when used for bleed prophylaxis and treatment in previously untreated/minimally treated patients (PUPs/MTPs). Methods In this phase III, multicenter, open-label, uncontrolled study, PUPs/MTPs (<6 years old) with severe hemophilia A received BAY 81–8973 (15–50 IU/kg) at least once weekly as prophylaxis. Primary efficacy endpoint was the annualized bleeding rate (ABR) within 48 hours after prophylaxis infusion. Adverse events and immunogenicity were assessed. Patients who developed inhibitors were offered immune tolerance induction (ITI) treatment in an optional extension phase. Results Fifty-two patients were enrolled, with 43 patients (mean age: 13.6 months) treated. Median (interqu...

Clinical and Applied Thrombosis/Hemostasis, 2020

Rivaroxaban after total knee arthroplasty (TKA) is used to prevent postoperative venous thromboem... more Rivaroxaban after total knee arthroplasty (TKA) is used to prevent postoperative venous thromboembolism (VTE); however, despite thromboprophylaxis, some patients still develop postoperative VTE. To determine whether tourniquet time, time to initiate rivaroxaban (TTIRIV), or Body Mass Index (BMI) was associated with postoperative VTE. A retrospective case-control study was conducted. Those patients that developed VTE despite prophylaxis (cases) were compared to controls (no VTE). A univariate analysis was conducted (p < 0.05 statistically significant). Seven VTE cases were identified from 234 TKA-patients. Patients with and without VTE had BMI of 40.1 ± 9.1 and 32.8 ± 7.5, respectively (p = 0.064). TTIRIV in VTE and control group was 28.2 ± 4.7 hours and 26.4 ± 4.2 hours, respectively (p = 0.39). Mean tourniquet time in VTE and control group was 65.0 ± 8.7 minutes and 49 ± 8.8 minutes, respectively (p = 0.0007). Statistically significant differences in tourniquet times were noted ...

Stroke, 2016

Background and Purpose— Among children with arterial ischemic stroke (AIS), those with arteriopat... more Background and Purpose— Among children with arterial ischemic stroke (AIS), those with arteriopathy have the highest recurrence risk. We hypothesized that arteriopathy progression is an inflammatory process and that inflammatory biomarkers would predict recurrent AIS. Methods— In an international study of childhood AIS, we selected cases classified into 1 of the 3 most common childhood AIS causes: definite arteriopathic (n=103), cardioembolic (n=55), or idiopathic (n=78). We measured serum concentrations of high-sensitivity C-reactive protein, serum amyloid A, myeloperoxidase, and tumor necrosis factor-α. We used linear regression to compare analyte concentrations across the subtypes and Cox proportional hazards models to determine predictors of recurrent AIS. Results— Median age at index stroke was 8.2 years (interquartile range, 3.6–14.3); serum samples were collected at median 5.5 days post stroke (interquartile range, 3–10 days). In adjusted models (including age, infarct volume...

Translational pediatrics, 2012

The number of children undergoing successful renal transplantations has been increasing steadily ... more The number of children undergoing successful renal transplantations has been increasing steadily and as a result; general pediatricians are now more likely to encounter children with a kidney allograft in their practice. Although the medical care immediately after transplantation is mostly provided by transplant teams, more and more outpatient care will eventually be performed at the patient's local community. Medical care from general pediatricians is particularly important, especially for children who are residing far from transplant centers. As these children require prolong immunosuppressive therapies and are susceptible to various specific clinical problems, it is imperative for their primary care providers and pediatricians to be knowledgeable about their specific needs and be competent in providing care. This article highlights the roles and common practice related issues that pertain to general pediatricians in the care of pediatric renal allograft recipients.

Stroke; a journal of cerebral circulation, Jan 10, 2015

Published cohorts of children with arterial ischemic stroke (AIS) in the 1990s to early 2000s rep... more Published cohorts of children with arterial ischemic stroke (AIS) in the 1990s to early 2000s reported 5-year cumulative recurrence rates approaching 20%. Since then, utilization of antithrombotic agents for secondary stroke prevention in children has increased. We sought to determine rates and predictors of recurrent stroke in the current era. The Vascular Effects of Infection in Pediatric Stroke (VIPS) study enrolled 355 children with AIS at 37 international centers from 2009 to 2014 and followed them prospectively for recurrent stroke. Index and recurrent strokes underwent central review and confirmation, as well as central classification of causes of stroke, including arteriopathies. Other predictors were measured via parental interview or chart review. Of the 355 children, 354 survived their acute index stroke, and 308 (87%) were treated with an antithrombotic medication. During a median follow-up of 2.0 years (interquartile range, 1.0-3.0), 40 children had a recurrent AIS, and...

Blood Coagulation & Fibrinolysis, 2017

Unfractionated heparin (UFH) and low molecular weight heparin (LMWH) are commonly used anticoagul... more Unfractionated heparin (UFH) and low molecular weight heparin (LMWH) are commonly used anticoagulants to treat thrombotic diseases. However, these anticoagulants are associated with some limitations such as increased bleeding, variable dose response, and the necessity for frequent monitoring. This led to the development of the antithrombin-heparin covalent complex (ATH) which has been shown to overcome many of these limitations. Numerous past studies have proven ATH to be a better anticoagulant in comparison to UFH. More recent studies aimed at studying its interaction with the fibrinolytic pathway. It was observed that ATH inhibited free and fibrin bound plasmin (Pn), the main serine protease of fibrinolysis. As well, the rates of Pn generation on fibrin clots decreased in the presence of ATH. These studies were conducted in purified systems and did not elucidate the interaction of ATH with Pn in the presence of its natural inhibitors, α 2-macroglobulin (α 2-M) and α 2-antiplasmin (α 2-AP). Thus, this study focuses on analyzing the effects of ATH in comparison to UFH and LMWH on Pn generation in plasma, to allow for a better understanding of such mechanisms under more physiological conditions. In comparison to the absence of anticoagulants, total Pn generated decreased in the presence of 0.7 U/ml of UFH or ATH and 2.1 U/ml of ATH. This confirms previous in vitro studies in which UFH + AT and ATH can inhibit Pn activity. In addition, quantified Pn bound α 2-M complexes showed a reduction at 0.7 U/ml of ATH suggesting that ATH may be able to compete with α 2-M for Pn. However, the amount of quantified Pn bound α 2-AP complexes were not affected as α 2-AP is a much faster inhibitor of Pn. It was noted that LMWH did not affect Pn generation. As a result, this study adds to our understanding of ATH mechanisms of action and aids in its development for clinical use.

International Journal of Pediatric Otorhinolaryngology, 2016

Objective: To review the thrombotic complications of head and neck infections, including Lemierre... more Objective: To review the thrombotic complications of head and neck infections, including Lemierre's syndrome, and their management. Methods: A retrospective review of pediatric patients presenting to McMaster Children's Hospital from 2009 to 2013 was undertaken. The literature was reviewed for evidence regarding the use of anticoagulation therapy in this population. Results: Eleven cases (6 males, 5 females) were identified. The median age was 10.9 (range 14 months e17 years). The most frequent head and neck infection causing a thrombotic complication was mastoiditis (n ¼ 6). All had thrombi identified on imaging, with the most common location being the sigmoid sinus (n ¼ 6) followed by the internal jugular vein (n ¼ 5). All 11 patients were anti-coagulated with low molecular weight heparin (LMWH) within a median of 2 days of diagnosis (average duration 105.8 days). Ten patients (90.9%) had thrombus improvement or resolution within a median of 3.4 months (range 1.0e13.9). Adverse sequelae from the thrombi were MCA infarct (n ¼ 1), septic pulmonary emboli (n ¼ 4), cranial nerve palsies (n ¼ 3) and Horner's syndrome (n ¼ 2). There were no adverse effects from anti-coagulation therapy. Review of the literature revealed anticoagulant use in 63.7% of pediatric cases reported since 2002. Conclusion: Anticoagulation remains controversial in the management of thrombotic complications from head and neck infections. Based on this case series, certain recommendations can be made regarding the benefits of anticoagulation, which appear to outweigh the risks. Further research is required to establish evidence for consensus in the antithrombotic management of thrombotic sequelae of head and neck infections.

The Journal of extra-corporeal technology, 2010

Cardiopulmonary bypass (CPB) creates a pro-coagulant state by causing platelet activation and inf... more Cardiopulmonary bypass (CPB) creates a pro-coagulant state by causing platelet activation and inflammation leading to thrombin generation and platelet dysfunction. It is associated with severe derangements in normal homeostasis resulting in both thrombotic and hemorrhagic complications. This derangement is greater in children with congenital heart disease than in adults because of the immaturity of the coagulation system, hemodilution of coagulation factors, hyperreactive platelets, and in some patients, physiologic changes associated with cyanosis. During CPB, an appropriate amount of heparin is given with the goal of minimizing the risk of thrombosis and platelet activation and at the same time reducing the risk of bleeding from over anticoagulation. In young children, this balance is more difficult to achieve because of inherent characteristics of the hemostatic system in these patients. Historically, protocols for heparin dosing and monitoring in children have been adapted from ...

American Journal of Physiology-Lung Cellular and Molecular Physiology, 2006

Coagulopathy and alveolar fibrin deposition are common in sick neonates and attributed to the pri... more Coagulopathy and alveolar fibrin deposition are common in sick neonates and attributed to the primary disease, as opposed to their ventilatory support. Hypothesizing that high tidal volume ventilation activates the extrinsic coagulation pathway, we air ventilated newborn and adult rats at low (10 ml/kg) or high (30 ml/kg) tidal volume and compared them with age-matched nonventilated controls. Blood was collected at the end of the experiment for measurement of clot time, tissue factor, and other coagulation factor content. Similar measurements were obtained from lung lavage material. The newborn clot time (44 ± 1) was lower and plasma tissue factor content higher (103.4 ± 0.4) than adults (88 ± 4 s and 26.6 ± 1.4 units; P < 0.01). High, but not low, tidal volume ventilation of newborns for as little as 15 min significantly reduced clot time and increased plasma tissue factor content ( P < 0.01). High volume ventilation increased plasma factor Xa (0.1 ± 0.1 to 1.6 ± 0.4 nM; P &l...

Thrombosis and Haemostasis, 2002

SummaryThrombin generation is decreased and delayed in plasma from newborns and children compared... more SummaryThrombin generation is decreased and delayed in plasma from newborns and children compared to adults. We hypothesized that lower doses of heparinoid anticoagulants are required to give similar thrombin generation in newborn (umbilical cord) and child plasmas compared to that of adults. Thrombin generation was performed in either the absence or presence of unfractionated heparin (UFH), low molecular weight heparin (LMWH) or a covalent antithrombin-heparin complex (ATH). After contact activation and recalcification of each plasma, thrombin activity was measured by periodic sub-sampling into chromogenic substrate. UFH inhibited thrombin generation to a greater extent compared to LMWH in all plasmas. Cord plasma was more sensitive to inhibition and displayed a greater difference in the effectiveness of UFH compared to LMWH than other plasmas. Lower concentrations of UFH and LMWH were required to inhibit thrombin generation in cord and child plasmas compared to adult plasma. In co...

Pediatrics, 2018

Cerebrovascular disease is among the top 10 causes of death in US children, but risk factors for ... more Cerebrovascular disease is among the top 10 causes of death in US children, but risk factors for mortality are poorly understood. Within an international registry, we identify predictors of in-hospital mortality after pediatric arterial ischemic stroke (AIS). Neonates (0-28 days) and children (29 days-<19 years) with AIS were enrolled from January 2003 to July 2014 in a multinational stroke registry. Death during hospitalization and cause of death were ascertained from medical records. Logistic regression was used to analyze associations between risk factors and in-hospital mortality. Fourteen of 915 neonates (1.5%) and 70 of 2273 children (3.1%) died during hospitalization. Of 48 cases with reported causes of death, 31 (64.6%) were stroke-related, with remaining deaths attributed to medical disease. In multivariable analysis, congenital heart disease (odds ratio [OR]: 3.88; 95% confidence interval [CI]: 1.23-12.29; = .021), posterior plus anterior circulation stroke (OR: 5.36; 9...

Blood Coagulation & Fibrinolysis, 2013

Intracranial hemorrhage (ICH) is a significant complication for children with hemophilia. Identif... more Intracranial hemorrhage (ICH) is a significant complication for children with hemophilia. Identifying risk factors may allow us to establish clinically relevant guidelines for the diagnosis and management of ICH. The purpose of this review is to nucleate evidence from the available literature on the incidence, risk factors, presentation, treatment, and outcomes of ICH that can be utilized to develop a clinically useful framework for the diagnosis and management of hemophiliac patients with the condition. An electronic MEDLINE and EMBASE literature search was undertaken using the key words 'intracranial hemorrhage and hemophilia' and setting limits as: Last 10 years and Review or Randomized Controlled Trial (RCT) or Clinical Trial, or Practice Guidelines. Following review of all articles using predetermined search words and criteria, 31 were retrieved with sufficient data to address our objectives. An algorithm is presented for the management of children (>-3 years-18 years) with hemophilia and suspected ICH. A standardized approach to ICH may reduce unnecessary exposure to radiation via computed tomography scan in a select group of children. Currently there is limited scientific evidence to recommend a diagnostic and therapeutic algorithm for neonates with hemophilia.

Journal of Thrombosis and Haemostasis, 2020

Annals of Neurology, 2009

Objective: Clinical trials are lacking in pediatric cerebral sinovenous thrombosis (CSVT). Neonat... more Objective: Clinical trials are lacking in pediatric cerebral sinovenous thrombosis (CSVT). Neonates and children increasingly receive anticoagulant therapy (ACT) based on adult studies. Safety data for ACT in pediatric CSVT are scant and urgently needed. The objective was to assess the safety and outcome of ACT in pediatric CSVT. Methods: In a single-center prospective study, neonates and children with CSVT received ACT (standard/low molecular weight heparin, warfarin) by standardized protocol. A study neuroradiologist (M.S.) assessed all initial and follow-up neuroimaging for intracranial hemorrhage (ICH), thrombus propagation, and recanalization. Clinical outcome was assessed with the Pediatric Stroke Outcome Measure. Results: Among 162 pediatric patients, 85 received ACT at diagnosis, including 29/83 (35%) neonates and 56/79 (71%) children. Major hemorrhage occurred in 6% (6/99) of treated patients, including 14% (3/21 neonates, 2/15 children) with and 2% (0/17 neonates, 1/46 children) without pretreatment ICH. ACT-associated bleeds were all nonfatal, and clinical outcome was favorable in 50%, similar to the remaining patients (53%). Early follow-up imaging demonstrated thrombus propagation in 11/57 neonates (10/35 [28%] without and 1/22 [4%] with ACT [p ϭ 0.037]) and 10/63 children (7/19 [37%] without and 3/44 [7%] with ACT [p ϭ 0.006]). Propagation was associated with new venous infarcts in 10% neonates and 40% children and worse clinical outcome in children (p ϭ 0.053). Recanalization occurred earlier and more completely in neonates (p ϭ 0.002). Clinical outcome was unfavorable in 47%. Interpretation: In pediatric CSVT, ACT appears safe. Nontreatment with ACT is associated with thrombus propagation, observed in 1 4 of untreated neonates and over 1 3 of children. Anticoagulants merit strong consideration in pediatric CSVT.

The Lancet Haematology, 2019

Background Treatment of venous thromboembolism in children is based on data obtained in adults wi... more Background Treatment of venous thromboembolism in children is based on data obtained in adults with little direct documentation of its efficacy and safety in children. The aim of our study was to compare the efficacy and safety of rivaroxaban versus standard anticoagulants in children with venous thromboembolism. Methods In a multicentre, parallel-group, open-label, randomised study, children (aged 0-17 years) attending 107 paediatric hospitals in 28 countries with documented acute venous thromboembolism who had started heparinisation were assigned (2:1) to bodyweight-adjusted rivaroxaban (tablets or suspension) in a 20-mg equivalent dose or standard anticoagulants (heparin or switched to vitamin K antagonist). Randomisation was stratified by age and venous thromboembolism site. The main treatment period was 3 months (1 month in children <2 years of age with catheter-related venous thromboembolism). The primary efficacy outcome, symptomatic recurrent venous thromboembolism (assessed by intention-to-treat), and the principal safety outcome, major or clinically relevant nonmajor bleeding (assessed in participants who received ≥1 dose), were centrally assessed by investigators who were unaware of treatment assignment. Repeat imaging was obtained at the end of the main treatment period and compared with baseline imaging tests. This trial is registered with ClinicalTrials.gov, number NCT02234843 and has been completed. Findings From Nov 14, 2014, to Sept 28, 2018, 500 (96%) of the 520 children screened for eligibility were enrolled. After a median follow-up of 91 days (IQR 87-95) in children who had a study treatment period of 3 months (n=463) and 31 days (IQR 29-35) in children who had a study treatment period of 1 month (n=37), symptomatic recurrent venous thromboembolism occurred in four (1%) of 335 children receiving rivaroxaban and five (3%) of 165 receiving standard anticoagulants (hazard ratio [HR] 0•40, 95% CI 0•11-1•41). Repeat imaging showed an improved effect of rivaroxaban on thrombotic burden as compared with standard anticoagulants (p=0•012). Major or clinically relevant non-major bleeding in participants who received ≥1 dose occurred in ten (3%) of 329 children (all non-major) receiving rivaroxaban and in three (2%) of 162 children (two major and one non-major) receiving standard anticoagulants (HR 1•58, 95% CI 0•51-6•27). Absolute and relative efficacy and safety estimates of rivaroxaban versus standard anticoagulation estimates were similar to those in rivaroxaban studies in adults. There were no treatment-related deaths. Interpretation In children with acute venous thromboembolism, treatment with rivaroxaban resulted in a similarly low recurrence risk and reduced thrombotic burden without increased bleeding, as compared with standard anticoagulants. Funding Bayer AG and Janssen Research & Development.

Pediatric Neurology, 2011

Pediatric ischemic stroke still represents a burden, and more than half of the survivors will exp... more Pediatric ischemic stroke still represents a burden, and more than half of the survivors will experience cognitive or motor disabilities. The objective of this study was to investigate the role of thrombophilia in a cohort of children with arterial ischemic stroke. The records of infants and children with clinically and radiologically confirmed stroke were reviewed. Patients with venous or perinatal

Acta Biomaterialia, 2010

Gold was used as a substrate for immobilization of an antithrombin-heparin (ATH) covalent complex... more Gold was used as a substrate for immobilization of an antithrombin-heparin (ATH) covalent complex to investigate ATH as a surface modifier to prevent blood coagulation. Three different surface modification methods were used to attach ATH to gold: (i) direct chemisorption; (ii) using dithiobis(succinimidyl propionate) (DSP) as a linker molecule and (iii) using polyethylene oxide (PEO) as a linker/spacer. The ATH-modified surfaces were compared to analogous heparinized surfaces. Water contact angles and X-ray photoelectron spectroscopy confirmed the modifications and provided data on surface properties and possible orientation. Ellipsometry measurements showed that surface coverage of DSP and PEO was high. ATH and heparin densities were quantified using radioiodination and quartz crystal microbalance, respectively. The surface density of ATH was greatest on the DSP surface (0.17 microg cm(-2)) and lowest on the PEO (0.05 microg cm(-2)). The low uptake on the PEO surface was likely due to the protein resistance of the PEO component. Using radioiodinated antithrombin (AT), it was shown that ATH-immobilized surfaces bound significantly greater amounts from both buffer and plasma than the analogous heparinized surfaces. Immunoblot analysis of proteins adsorbed from plasma demonstrated that surfaces chemisorbed with PEO, whether or not subsequently modified with ATH, inhibited non-specific adsorption. The immunoblot response for AT was stronger on the DSP-ATH than on the heparin surfaces, thus confirming the results from radiolabelling. The ATH surfaces again showed higher selectivity for AT binding than analogous heparin-modified surfaces, indicating the enhanced anticoagulant potential of ATH for biomaterial surface modification.