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Alami J, Feldman HA, Hanson A, Kumar R, Sola-Visner M, Davenport P. Efficacy and safety of antithrombin supplementation in neonates and infants on a continuous heparin infusion. Res Pract Thromb Haemost 2024; 8:102336. [PMID: 38440263 PMCID: PMC10909641 DOI: 10.1016/j.rpth.2024.102336] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Revised: 01/01/2024] [Accepted: 01/22/2024] [Indexed: 03/06/2024] Open
Abstract
Background Antithrombin (AT) is a natural anticoagulant and potent inhibitor of several coagulation proteins, including activated factor X (FXa) and FIIa. The therapeutic activity of heparin depends on the presence of AT. Levels of plasma AT are low in neonates and young infants compared to those in adults. Exogenous AT supplementation is postulated to enhance the activity of heparin and facilitate attainment of therapeutic anticoagulation in infants. Objectives To describe the efficacy and safety of AT administration in infants on a continuous heparin infusion. Methods Retrospective cohort study of 50 infants who received AT while on a heparin infusion. The primary efficacy outcome was attainment of therapeutic anticoagulation within 48 hours after AT administration. Secondary outcomes included the percent of partial thromboplastin time (PTT) levels and/or antifactor Xa (anti-FXa) activity within the therapeutic window, attainment of the target AT activity level, the incidence and severity of bleeding, and all-cause in-hospital mortality. A secondary analysis investigated the relationship between simultaneously measured PTT levels and anti-FXa activity used for heparin monitoring. Results AT supplementation resulted in achievement of at least one therapeutic PTT level or anti-FXa activity in 90% of AT courses, though not sustained. PTT was within the therapeutic window more often than anti-FXa activity. When measured simultaneously, therapeutic anti-FXa levels were associated with supratherapeutic PTT levels. Conclusion AT supplementation in infants on a continuous heparin infusion may transiently improve the therapeutic effect of heparin, but this is largely dependent on the laboratory parameters used for monitoring.
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Affiliation(s)
- Jennifer Alami
- Department of Pharmacy, Boston Children’s Hospital, Boston, Massachusetts, USA
| | - Henry A. Feldman
- Institutional Centers for Clinical and Translational Research, Boston Children’s Hospital, Boston, Massachusetts, USA
- Division of Newborn Medicine, Boston Children’s Hospital, Boston, Massachusetts, USA
| | - Alison Hanson
- Department of Pharmacy, Boston Children’s Hospital, Boston, Massachusetts, USA
| | - Riten Kumar
- Dana Farber/Boston Children’s Cancer and Blood Disorders Center, Boston, Massachusetts, USA
| | - Martha Sola-Visner
- Division of Newborn Medicine, Boston Children’s Hospital, Boston, Massachusetts, USA
| | - Patricia Davenport
- Division of Newborn Medicine, Boston Children’s Hospital, Boston, Massachusetts, USA
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2
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Morgan CT, Chetan D, Varenbut J, Haller C, Seed M, Mertens LL, Honjo O. Mechanical atrioventricular valve replacement in patients with single ventricle palliation. Eur J Cardiothorac Surg 2023; 64:ezad317. [PMID: 37707524 DOI: 10.1093/ejcts/ezad317] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/01/2023] [Revised: 07/26/2023] [Accepted: 09/12/2023] [Indexed: 09/15/2023] Open
Abstract
OBJECTIVES Atrioventricular valve (AVV) replacements in patients with single-ventricle circulations pose significant surgical risks and are associated with high morbidity and mortality. METHODS From 1997 to 2021, 16 consecutive patients with functionally single-ventricle physiology underwent mechanical AVV replacement. Primary outcome was transplant-free survival. Secondary outcomes included major postoperative morbidity. RESULTS The median age of AVV replacement was 2 years old (interquartile range 0.6-3.8 years). All AVV replacements were performed with a St. Jude Medical mechanical valve, median 24 mm (range, 19-31mm). Extracorporeal membrane oxygenation (ECMO) was required in 4 patients. Operative mortality was 38% (6/16). There were 2 late deaths and 3 transplants. Transplant-free survival was 50% at 1 year, 37.5% at 5 years, and 22% at 10 years. Transplant-free survival was higher for patients with preserved ventricular function (P = 0.01). Difference in transplant-free survival at 1 year was 75% vs 25%, at 5 years was 62.5% vs 12.5% and at 10 years was 57% vs 0%. Three (19%) patients had complete heart block requiring permanent pacemaker insertion. 6 of 13 patients (46%) patients reached Fontan completion (3 patients operated at/after Fontan). Significant bleeding events occurred in 8 patients (50%) with 3 patients suffering major cerebrovascular accidents. There were 6 events of valve thrombosis in 5 patients, resulting in 2 deaths and 2 heart transplants. CONCLUSIONS Mechanical valve replacement carries significant morbidity and mortality risk. While it successfully salvages about half of patients with preserved ventricular function, careful consideration of alternative options should be made before embarking upon mechanical valve replacement.
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Affiliation(s)
- Conall T Morgan
- Division of Cardiology, The Labatt Family Heart Centre, The Hospital for Sick Children
- Department of Pediatrics, University of Toronto
| | - Devin Chetan
- Division of Cardiology, The Labatt Family Heart Centre, The Hospital for Sick Children
- Department of Pediatrics, University of Toronto
| | - Jaymie Varenbut
- Division of Cardiovascular Surgery, The Labatt Family Heart Centre, The Hospital for Sick Children, Toronto, ON, Canada
- Department of Surgery, University of Toronto
| | - Christoph Haller
- Division of Cardiovascular Surgery, The Labatt Family Heart Centre, The Hospital for Sick Children, Toronto, ON, Canada
- Department of Surgery, University of Toronto
| | - Mike Seed
- Division of Cardiology, The Labatt Family Heart Centre, The Hospital for Sick Children
- Department of Pediatrics, University of Toronto
| | - Luc L Mertens
- Division of Cardiology, The Labatt Family Heart Centre, The Hospital for Sick Children
- Department of Pediatrics, University of Toronto
| | - Osami Honjo
- Division of Cardiovascular Surgery, The Labatt Family Heart Centre, The Hospital for Sick Children, Toronto, ON, Canada
- Department of Surgery, University of Toronto
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3
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Jones S, Hislop JL, Gilmore H, Greenway A, Hibbard J, Monagle P, Newall F. Using an electronic medical record patient portal for warfarin self-management: Empowering children and parents. Res Pract Thromb Haemost 2023; 7:100066. [PMID: 36891277 PMCID: PMC9986642 DOI: 10.1016/j.rpth.2023.100066] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2022] [Revised: 12/09/2022] [Accepted: 01/08/2023] [Indexed: 02/05/2023] Open
Abstract
Background Many children taking warfarin perform their international normalized ratio (INR) at home, with results phoned to a clinician who instructs warfarin dosing. Data suggest that parents can be supported to make warfarin dosing decisions themselves, a process known as patient self-management (PSM). Objectives This study aimed to determine the suitability and acceptability of warfarin PSM in children using the Epic Patient Portal. Methods Children currently performing INR patient self-testing were eligible. Participation involved an individualized education session, adherence to the PSM program, and participation in phone interviews. Clinical outcomes (INR time in therapeutic range and safety outcomes), patient portal functionality, and family experience were assessed. The hospital human research ethics committee approved the study and consent was obtained from parents/guardians. Results Twenty-four families undertook PSM. The median age of children was 11 years and all children had congenital heart disease. A median of 13 INRs was uploaded to the portal per family (range, 8-47) across a 10-month period. Before PSM, the mean time the INR was in therapeutic range was 71%; this increased to 79.9% during PSM (difference: P < .001). No adverse events were encountered. Eight families participated in a phone interview. The major theme identified was empowerment; minor themes that emerged included "gaining knowledge," "trust and responsibility builds confidence," "saving time," and "resources as a safety net." Conclusion This study demonstrates that communication via the Epic Patient Portal is satisfactory to families and offers a suitable option for PSM for children. Importantly, PSM empowers and builds confidence in families to facilitate management of their child's health.
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Affiliation(s)
- Sophie Jones
- Department of Nursing, The University of Melbourne, Melbourne, Australia.,Haematology Research, Murdoch Children's Research of Institute, Melbourne, Australia.,Department of Clinical Haematology, Royal Children's Hospital, Melbourne, Australia
| | - Jodi L Hislop
- Haematology Research, Murdoch Children's Research of Institute, Melbourne, Australia
| | - Hollie Gilmore
- Department of Clinical Haematology, Royal Children's Hospital, Melbourne, Australia
| | - Anthea Greenway
- Haematology Research, Murdoch Children's Research of Institute, Melbourne, Australia.,Department of Clinical Haematology, Royal Children's Hospital, Melbourne, Australia
| | | | - Paul Monagle
- Haematology Research, Murdoch Children's Research of Institute, Melbourne, Australia.,Department of Clinical Haematology, Royal Children's Hospital, Melbourne, Australia.,Kids Cancer Centre, Sydney Children's Hospital, Randwick, Australia.,Department of Paediatrics, University of Melbourne, Melbourne, Australia
| | - Fiona Newall
- Department of Nursing, The University of Melbourne, Melbourne, Australia.,Haematology Research, Murdoch Children's Research of Institute, Melbourne, Australia.,Department of Clinical Haematology, Royal Children's Hospital, Melbourne, Australia.,Department of Paediatrics, University of Melbourne, Melbourne, Australia.,Nursing Research Department, Royal Children's Hospital, Melbourne, Australia
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Chegondi M, Vijayakumar N, Totapally BR. Management of Anticoagulation during Extracorporeal Membrane Oxygenation in Children. Pediatr Rep 2022; 14:320-332. [PMID: 35894028 PMCID: PMC9326610 DOI: 10.3390/pediatric14030039] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2022] [Revised: 06/20/2022] [Accepted: 07/01/2022] [Indexed: 02/04/2023] Open
Abstract
Extracorporeal Membrane Oxygenation (ECMO) is often used in critically ill children with severe cardiopulmonary failure. Worldwide, about 3600 children are supported by ECMO each year, with an increase of 10% in cases per year. Although anticoagulation is necessary to prevent circuit thrombosis during ECMO support, bleeding and thrombosis are associated with significantly increased mortality risk. In addition, maintaining balanced hemostasis is a challenging task during ECMO support. While heparin is a standard anticoagulation therapy in ECMO, recently, newer anticoagulant agents are also in use. Currently, there is a wide variation in anticoagulation management and diagnostic monitoring in children receiving ECMO. This review intends to describe the pathophysiology of coagulation during ECMO support, review of literature on current and newer anticoagulant agents, and outline various diagnostic tests used for anticoagulation monitoring. We will also discuss knowledge gaps and future areas of research.
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Affiliation(s)
- Madhuradhar Chegondi
- Division of Pediatric Critical Care Medicine, Stead Family Children’s Hospital, University of Iowa, Iowa City, IA 52242, USA
- Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
| | - Niranjan Vijayakumar
- Division of Cardiac Critical Care, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA;
| | - Balagangadhar R. Totapally
- Division of Critical Care Medicine, Nicklaus Children’s Hospital, Miami, FL 33155, USA;
- Herbert Wertheim College of Medicine, Florida International University, Miami, FL 33199, USA
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5
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Harada A, Kurobe M. Neonatal portal thrombosis in biliary atresia after Kasai procedure. Pediatr Int 2022; 64:e15262. [PMID: 35938607 DOI: 10.1111/ped.15262] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2022] [Revised: 04/22/2022] [Accepted: 05/29/2022] [Indexed: 01/05/2023]
Affiliation(s)
- Atsushi Harada
- Department of Pediatric Surgery, Kawaguchi Municipal Medical Center, Saitama, Japan
| | - Masashi Kurobe
- Division of Pediatric Surgery, Department of Surgery, The Jikei University School of Medicine, Tokyo, Japan
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6
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Erol S, Aydın B, Cinar HG, Yoldas T, Zenciroglu A. Arterial Thrombosis Secondary to Cardiac Catheterization in Neonates. DICLE MEDICAL JOURNAL 2019. [DOI: 10.5798/dicletip.534847] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
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Abstract
OBJECTIVE The objective of this article was to evaluate neonates diagnosed systemic thrombosis and their outcomes. METHODS We retrospectively evaluated data of neonatal systemic thrombosis between January 2011 and December 2016. RESULTS Among 4376 hospitalized, 30 neonates (0.69%) were diagnosed systemic thrombosis. Their mean birth weight was 2422±1152 g (680 to 4750 g), gestational age was 35±5.4 weeks (25 to 41 wk). There were 25 neonates (83.3%) with venous, 5 patients (16.7%) with arterial thrombosis. The most common sites that thrombi localized were major vessels (n=11) and central nervous system (n=8). Central catheter insertion (76.7%) and prematurity (46.7%) were the most common risk factors. Congenital prothrombotic risk factors included G1691A mutation in factor V Leiden (n=1), mutation in factor XIII (n=1), C677T mutation in methylenetetrahydrofolate reductase (n=6). More than 1 congenital risk factor was identified in 5 patients. The patients were treated with low-molecular weight heparin. The mortality rate was 13.3% (n=4). Two patients required amputation (left foot, left upper extremity). Unilateral renal atrophy (n=1), cerebral palsy (n=2), hemiparesis (n=1) were identified among followed 24 patients. CONCLUSIONS Critically ill neonates are at risk for thrombosis, and devastating consequences can result. As indwelling catheters and prematurity are important, careful monitorization, early diagnosis and therapy, cautious care of central catheter might reduce the incidence and adverse outcome.
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Bhatia AK, Yabrodi M, Carroll M, Bunting S, Kanter K, Maher KO, Deshpande SR. Utility and correlation of known anticoagulation parameters in the management of pediatric ventricular assist devices. World J Cardiol 2017; 9:749-756. [PMID: 29081908 PMCID: PMC5633539 DOI: 10.4330/wjc.v9.i9.749] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2017] [Revised: 07/20/2017] [Accepted: 08/02/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To assess utility and correlation of known anticoagulation parameters in the management of pediatric ventricular assist device (VAD).
METHODS Retrospective study of pediatric patients supported with a Berlin EXCOR VAD at a single pediatric tertiary care center during a single year.
RESULTS We demonstrated associations between activated thromboplastin time (aPTT) and R-thromboelastography (R-TEG) values (rs = 0.65, P < 0.001) and between anti-Xa assay and R-TEG values (rs = 0.54, P < 0.001). The strongest correlation was seen between aPTT and anti-Xa assays (rs = 0.71, P < 0.001). There was also a statistically significant correlation between platelet counts and the maximum amplitude of TEG (rs = 0.71, P < 0.001). Importantly, there was no association between dose of unfractionated heparin and either measure of anticoagulation (aPTT, anti-Xa or R-TEG value).
CONCLUSION This study suggests that while there is strong correlation between aPTT, anti-Xa assay and R-TEG values for patients requiring VAD support, there is a lack of relevant correlation between heparin dose and degree of effect. This raises concern as various guidelines continue to recommend using these parameters to titrate heparin therapy.
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Affiliation(s)
- Ajay K Bhatia
- Division of Pediatric Cardiology, Emory University School of Medicine, Children’s Healthcare of Atlanta, Atlanta, GA 30322, United States
| | - Mouhammad Yabrodi
- Division of Pediatric Cardiology, Emory University School of Medicine, Children’s Healthcare of Atlanta, Atlanta, GA 30322, United States
| | - Mallory Carroll
- Mechanical Circulatory Support Program, Children’s Healthcare of Atlanta, Atlanta, GA 30322, United States
| | - Silvia Bunting
- Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322, United States
| | - Kirk Kanter
- Department of Cardiothoracic Surgery, Emory University School of Medicine, Atlanta, GA 30322, United States
| | - Kevin O Maher
- Division of Pediatric Cardiology, Emory University School of Medicine, Children’s Healthcare of Atlanta, Atlanta, GA 30322, United States
| | - Shriprasad R Deshpande
- Division of Pediatric Cardiology, Emory University School of Medicine, Children’s Healthcare of Atlanta, Atlanta, GA 30322, United States
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Moynihan K, Johnson K, Straney L, Stocker C, Anderson B, Venugopal P, Roy J. Coagulation monitoring correlation with heparin dose in pediatric extracorporeal life support. Perfusion 2017; 32:675-685. [DOI: 10.1177/0267659117720494] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
Objectives: Extracorporeal Life Support (ECLS) risks thrombotic and hemorrhagic complications. Optimal anti-coagulation monitoring is controversial. We compared coagulation tests evaluating the heparin effect in pediatric ECLS. Methods: A retrospective study of children (<18yrs) undergoing ECLS over 12 months in a tertiary pediatric intensive care unit (PICU). Variables included anti-Factor Xa activity (anti-Xa), activated partial thromboplastin time (aPTT), activated clotting time (ACT) and thromboelastogram (TEG®6s) parameters: ratio and delta reaction (R) times (the ratio and difference, respectively, between R times in kaolin assays with and without heparinase). Test results were correlated with unfractionated heparin infusion rate (IU/kg/hr) at the time of sampling. Mean test results of each ECLS run were evaluated according to the presence/absence of complications. Results: Thirty-two ECLS runs (31 patients) generated 695 data-points for correlation. PICU mortality was 22% and the thrombotic complication rate was 66%. The proportion of variation in coagulation test results explained by heparin dose was 13.3% for anti-Xa, 11.9% for ratio R time, and 9.9% for delta R time, compared with <1% for ACT and aPTT. Incorporating individual variation, age and antithrombin activity in a model with heparin dose explained less than 50% of the variation in test results. Correlation varied according to age, day of ECLS run and between individuals, with parallel dose-response lines noted between patients. Significantly lower mean anti-Xa was observed in PICU non-survivors and runs with thrombosis. Conclusion: Lower anti-Xa was observed in ECLS runs with complications. Although absolute results from anti-Xa and TEG6®s showed the best correlation with heparin dose, a large proportion of variation in results was unexplained by heparin, while dose response was similar between individuals. Population pharmacokinetic/pharmacodynamic modelling is required, as well as prospective trials to delineate the superior means of adjusting heparin therapy to prevent adverse clinical outcomes.
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Affiliation(s)
- Katie Moynihan
- Pediatric Intensive Care Unit, Lady Cilento Children’s Hospital (LCCH), Brisbane, Australia
- Pediatric Critical Care Research Group, LCCH, Brisbane, Australia
- University of Queensland School of Medicine, Brisbane, Australia
| | - Kerry Johnson
- Pediatric Intensive Care Unit, Lady Cilento Children’s Hospital (LCCH), Brisbane, Australia
| | - Lahn Straney
- Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Australia
| | - Christian Stocker
- Pediatric Intensive Care Unit, Lady Cilento Children’s Hospital (LCCH), Brisbane, Australia
- Pediatric Critical Care Research Group, LCCH, Brisbane, Australia
- University of Queensland School of Medicine, Brisbane, Australia
- Queensland Neonatal & Pediatric ECLS Service, LCCH, Brisbane, Australia
| | - Ben Anderson
- Queensland Neonatal & Pediatric ECLS Service, LCCH, Brisbane, Australia
| | - Prem Venugopal
- Queensland Neonatal & Pediatric ECLS Service, LCCH, Brisbane, Australia
| | - John Roy
- University of Queensland School of Medicine, Brisbane, Australia
- Pathology Queensland, Brisbane, Australia
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Malec L, Young G. Treatment of Venous Thromboembolism in Pediatric Patients. Front Pediatr 2017; 5:26. [PMID: 28293549 PMCID: PMC5328974 DOI: 10.3389/fped.2017.00026] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2016] [Accepted: 02/01/2017] [Indexed: 01/19/2023] Open
Abstract
Given the increased incidence of venous thromboembolism (VTE) in pediatric patients, which has been associated with increased survival of medically complex patients and increased use of invasive supportive measures, it is important to understand treatment options and unique aspects of anticoagulant use in children. The objective of this mini-review is to outline the goals of treatment, treatment options, and adverse events associated with the use of anticoagulants in pediatric patients with VTE.
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Affiliation(s)
- Lynn Malec
- BloodCenter of Wisconsin, Milwaukee, WI, USA; Medical College of Wisconsin, Milwaukee, WI, USA
| | - Guy Young
- Department of Pediatrics, Division of Hematology, Children's Hospital of Los Angeles , Los Angeles, CA , USA
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Muster I, Haas T, Quandt D, Kretschmar O, Knirsch W. Factors Influencing ACT After Intravenous Bolus Administration of 100 IU/kg of Unfractionated Heparin During Cardiac Catheterization in Children. Clin Appl Thromb Hemost 2016; 23:740-747. [PMID: 27514640 DOI: 10.1177/1076029616660761] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
Anticoagulation using intravenous bolus administration of unfractionated heparin (UFH) aims to prevent thromboembolic complications in children undergoing cardiac catheterization (CC). Optimal UFH dosage is needed to reduce bleeding complications. We analyzed the effect of bolus UFH on activated clotting time (ACT) in children undergoing CC focusing on age-dependent, anesthesia-related, or disease-related influencing factors. This retrospective single-center study of 183 pediatric patients receiving UFH during CC analyzed ACT measured at the end of CC. After bolus administration of 100 IU UFH/kg body weight, ACT values between 105 and 488 seconds were reached. Seventy-two percent were within target level of 160 to 240 seconds. Age-dependent differences were not obtained ( P = .407). The ACT values were lower due to hemodilution (total fluid and crystalloid administration during CC, both P < .001), with premedication of acetylsalicylic acid ( P = .014) and low-molecular-weight heparin ( P = .049). Arterial thrombosis (3.85%), venous thrombosis (0.55%), and bleeding (1.65%) following CC did not correlate with ACT values but occurred more frequently in children between 1 month and 1 year of age (91%). In conclusion, with a bolus of 100 IU UFH/kg, an ACT target level of 160 to 240 seconds can be achieved during CC in children in 72%, which is influenced by hemodilution and anticoagulant and antiplatelet premedication but not by age.
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Affiliation(s)
- Ileana Muster
- 1 Pediatric Cardiology, Pediatric Heart Center, University Children's Hospital Zurich, Zurich, Switzerland
- 2 Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland
| | - Thorsten Haas
- 2 Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland
- 3 Anesthesiology, University Children's Hospital Zurich, Zurich, Switzerland
| | - Daniel Quandt
- 1 Pediatric Cardiology, Pediatric Heart Center, University Children's Hospital Zurich, Zurich, Switzerland
- 2 Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland
| | - Oliver Kretschmar
- 1 Pediatric Cardiology, Pediatric Heart Center, University Children's Hospital Zurich, Zurich, Switzerland
- 2 Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland
- Oliver Kretschmar and Walter Knirsch contributed as senior authors
| | - Walter Knirsch
- 1 Pediatric Cardiology, Pediatric Heart Center, University Children's Hospital Zurich, Zurich, Switzerland
- 2 Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland
- Oliver Kretschmar and Walter Knirsch contributed as senior authors
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Antithrombin Concentrate Use in Children Receiving Unfractionated Heparin for Acute Thrombosis. J Pediatr 2015; 167:645-9. [PMID: 26148660 DOI: 10.1016/j.jpeds.2015.06.006] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2015] [Revised: 05/07/2015] [Accepted: 06/03/2015] [Indexed: 02/04/2023]
Abstract
OBJECTIVE To characterize features of antithrombin concentrate (ATC) use in children receiving unfractionated heparin (UFH) therapy for acute thrombosis. STUDY DESIGN All pediatric patients at Texas Children's Hospital who received ATC in the context of UFH therapy for acute thrombosis during February 2011 to May 2013 were analyzed. RESULTS Fifty-one children received ATC during UFH therapy for acute thrombosis. Median age was 3 months (IQR 1 to 18 months). Clinical indications included venous (53%), arterial (37%), venous and arterial (6%), and intracardiac (4%) thrombosis. Median baseline antithrombin (AT) level was 61% and UFH dose was 26 U/kg/h. The median dose of ATC was 49.9 IU/kg (IQR 32.6 to 50.0 IU/kg). Although most patients (86%) did not undergo a change in UFH dose, there was a significant increase in both AT and anti-factor Xa level after the first dose of ATC (P < .001 for both). There was no correlation between ATC dose or increment in AT level above baseline and the achievement of targeted anticoagulation by anti-factor X activity level. Adverse bleeding events occurred in 10% of patients. CONCLUSIONS There was a significant change in AT and anti-factor Xa activity level after a single dose of ATC despite little to no change in dose of UFH. ATC appears to facilitate anticoagulation with UFH in some children with acute thrombosis but the degree of response is variable and dependent on factors identified in this study. Bleeding and other theoretical risks must be carefully considered.
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Giglia TM, Massicotte MP, Tweddell JS, Barst RJ, Bauman M, Erickson CC, Feltes TF, Foster E, Hinoki K, Ichord RN, Kreutzer J, McCrindle BW, Newburger JW, Tabbutt S, Todd JL, Webb CL. Prevention and Treatment of Thrombosis in Pediatric and Congenital Heart Disease. Circulation 2013; 128:2622-703. [DOI: 10.1161/01.cir.0000436140.77832.7a] [Citation(s) in RCA: 202] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
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Abstract
Extracorporeal life support applications have evolved considerably in recent years. However, the blood-biomaterial interface remains incompletely understood, and management of the acute inflammatory response and coagulation pathways continues to be challenging. At present, the gold standard for anticoagulation is unfractionated heparin. Since the inception of extracorporeal life support, the mainstay for anticoagulation monitoring has been activated clotting time. However, alongside the technological evolution in extracorporeal life support, the methods for monitoring heparin have also become more sophisticated, adding additional layers of complexity to creating an ideal safe protocol for anticoagulation during extracorporeal life support. To address this, the Extracorporeal Life Support Organization has formed an Anticoagulation Task Force to help direct both a consensus statement and potential guidelines within which the multiple monitoring methods can be customized for extracorporeal life support. One key question that remains in the use of these monitoring methods is whether the objective during extracorporeal life support is to anticoagulate the circuit to prevent thrombus formation within the extracorporeal device or whether it is to systemically anticoagulate the patient. This review details all current monitoring methods and highlights how they can be used during pediatric mechanical circulatory support.
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Crone E, Saliba N, George S, Hume E, Newall F, Jones S. Commencement of warfarin therapy in children following the Fontan procedure. Thromb Res 2013; 131:304-7. [DOI: 10.1016/j.thromres.2013.01.018] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2012] [Revised: 12/18/2012] [Accepted: 01/14/2013] [Indexed: 01/21/2023]
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Gómez JJ, Vallejo E, Palma MA, Rojas JP. Manejo exitoso con stent en un prematuro con síndrome de vena cava superior. Reporte de caso. REVISTA COLOMBIANA DE CARDIOLOGÍA 2012. [DOI: 10.1016/s0120-5633(12)70133-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022] Open
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Goldman J, Becker ML, Jones B, Clements M, Leeder JS. Development of biomarkers to optimize pediatric patient management: what makes children different? Biomark Med 2012; 5:781-94. [PMID: 22103612 DOI: 10.2217/bmm.11.96] [Citation(s) in RCA: 45] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
Despite the frequent utilization of biomarkers in medical practice, there is a relative paucity of information regarding validated pediatric biomarkers. Frequently, biomarkers found to be efficacious in adults are extrapolated to the pediatric clinical setting without considering that the pathogenesis of many diseases is distinctly different in children, and ontogeny directly influences disease evolution and therapeutic response in children. New and innovative approaches are necessary to provide reliable, validated biomarkers that can be used to improve and advance pediatric medical care.
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Affiliation(s)
- Jennifer Goldman
- Division of Clinical Pharmacology & Medical Toxicology, Children's Mercy Hospitals & Clinics & University of Missouri-Kansas City, Kansas City, MO, USA
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Hakacova N, Björkhem G, Hanséus K. Transition from acenocoumarol to warfarin in a 12-year-old child. CONGENIT HEART DIS 2011; 6:661-4. [PMID: 21501391 DOI: 10.1111/j.1747-0803.2011.00516.x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
The types of coumadin anticoagulants registered and available for use differ between countries. Most frequently used coumadin anticoagulants are warfarin and acenocoumarol. Under several specific conditions, transition from one coumarin to another is required. Because of different pharmacokinetic and pharmacodynamic characteristics, the transition from one type of coumarol to another type can be challenging. There are no studies that address this issue in children. We present the case report of transition treatment between acenocoumarol and warfarin in a 12-year-old child with prosthetic mitral valve.
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Affiliation(s)
- Nina Hakacova
- Department of Pediatric Cardiology, Children's Heart Center, Skane University Hospital, Lund, Sweden.
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Jones S, Newall F, Manias E, Monagle P. Assessing outcome measures of oral anticoagulation management in children. Thromb Res 2011; 127:75-80. [DOI: 10.1016/j.thromres.2010.09.001] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/02/2010] [Revised: 08/19/2010] [Accepted: 09/01/2010] [Indexed: 11/29/2022]
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Abstract
The number of children receiving anticoagulation is increasing. Thromboembolic events are associated with significant risk of morbidity and mortality although the optimal management of asymptomatic events remains unclear. Specific challenges in paediatrics include the diagnosis of thrombosis, delivery and monitoring of anticoagulation in a wide range of ages from neonates through to adolescents. The development of the haemostatic system as children age results in changing pathophysiology of thrombosis and response to anticoagulation agents. Although registry and observational studies have provided vital information, specific paediatric, prospective anticoagulation studies have been few and limited in design. The result is that much of current practice is extrapolated from adult studies. Traditional anticoagulants have significant limitations. Both heparin and warfarin are in widespread use but many fundamental questions regarding dose, therapeutic range, efficacy and optimum duration have not been fully answered. Alternative agents, such as direct thrombin inhibitors and the selective anti-factor Xa inhibitor fondaparinux, may have advantages for children. Clinical trials in adults and preliminary data in children are promising but caution should be applied until specific paediatric studies have demonstrated safety and efficacy.
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Affiliation(s)
- Jeanette H Payne
- Department of Paediatric Haematology, Sheffield Children's Hospital, Sheffield, UK.
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Veldman A, Nold MF, Michel-Behnke I. Thrombosis in the critically ill neonate: incidence, diagnosis, and management. Vasc Health Risk Manag 2009; 4:1337-48. [PMID: 19337547 PMCID: PMC2663458 DOI: 10.2147/vhrm.s4274] [Citation(s) in RCA: 69] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Among children, newborn infants are most vulnerable to development of thrombosis and serious thromboembolic complications. Amongst newborns, those neonates who are critically ill, both term and preterm, are at greatest risk for developing symptomatic thromboembolic disease. The most important risk factors are inflammation, DIC, impaired liver function, fluctuations in cardiac output, and congenital heart disease, as well as exogenous risk factors such as central venous or arterial catheters. In most clinically symptomatic infants, diagnosis is made by ultrasound, venography, or CT or MRI angiograms. However, clinically asymptomatic vessel thrombosis is sometimes picked up by screening investigations or during routine imaging for other indications. Acute management of thrombosis and thromboembolism comprises a variety of approaches, including simple observation, treatment with unfractionated or low molecular weight heparin, as well as more aggressive interventions such as thrombolytic therapy or catheter-directed revascularization. Long-term follow-up is dependent on the underlying diagnosis. In the majority of infants, stabilization of the patients’ general condition and hemodynamics, which allows removal of indwelling catheters, renders long-term anticoagulation superfluous. Nevertheless, in certain types of congenital heart disease or inherited thrombophilia, long-term prophylaxis may be warranted. This review article focuses on pathophysiology, diagnosis, and acute and long-term management of thrombosis in critically ill term and preterm neonates.
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Affiliation(s)
- Alex Veldman
- Monash Newborn and Ritchie Centre for Baby Health Research, Monash Medical Centre and Monash Institute of Medical Research, 246 Clayton Road, Clayton 3168, Melbourne, VIC, Australia.
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23
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Assessment of bone mineral density and markers of bone turnover in children under long-term oral anticoagulant therapy. J Pediatr Hematol Oncol 2008; 30:592-7. [PMID: 18799935 DOI: 10.1097/mph.0b013e31817541a8] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
Oral anticoagulants antagonize vitamin K action and potentially impair the carboxylation of osteocalcin, a protein essential for normal bone matrix formation. In the present study, bone mineral density (BMD) and bone turnover markers were evaluated in 23 children under long-term oral anticoagulant therapy. BMD of the lumbar spine was assessed (Dual Energy x-ray Absorptiometry) and reported as z score. Osteoblast [bone alkaline phosphatase, osteocalcin (Gla-Oc), amino-terminal procollagen 1 extension peptide] and osteoclast (urinary calcium and deoxypyridinoline, serum cross-linked C telopeptide) activity markers were measured. Vitamin D {[25(OH) D], parathormone, calcium, phosphorus, magnesium} and vitamin K status [factors II, VII, IX, X, protein C, protein S, undercarboxylated osteocalcin (Glu-Oc)] were determined. The above parameters were also evaluated in 25 healthy controls. Patients presented with higher levels in Glu-Oc, parathormone, and bone resorption markers, lower levels in bone formation markers and 25(OH) D, whereas 52% of them showed signs of osteopenia (-1>BMD z score>-2.5). Statistical analysis demonstrated that anticoagulant therapy was an independent predictor of alterations in Glu-Oc, Gla-Oc, bone alkaline phosphatase, amino-terminal procollagen 1 extension peptide, and serum cross-linked C telopeptide levels. It seems that long-term use of coumarin derivatives may cause osteopenia in children with the risk of developing osteoporosis later in life.
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Morales JP, Sabharwal T, Tibby SM, Burnand KG. Successful thrombolysis of a symptomatic neonatal aortic thrombosis associated with hypernatraemic dehydration--case report and literature review. Int J Clin Pract 2008; 62:502-5. [PMID: 18261079 DOI: 10.1111/j.1742-1241.2005.00810.x] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
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Bendaly EA, Batra AS, Ebenroth ES, Hurwitz RA. Outcome of cardiac thrombi in infants. Pediatr Cardiol 2008; 29:95-101. [PMID: 17768648 DOI: 10.1007/s00246-007-9036-8] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2007] [Accepted: 06/18/2007] [Indexed: 10/22/2022]
Abstract
Use of central lines in the neonatal intensive care unit (NICU) has led to the formation of intracardiac thrombi. A paucity of data exists on the management of neonatal cardiac thrombi, with the few reported cases focusing on outcomes following thrombolytic therapy. This study was undertaken to evaluate the outcome of cardiac thrombi in neonates who do not receive thrombolytic therapy. Nineteen patients younger than 3 months of age diagnosed with cardiac thrombi were included. All 19 patients had a central line. Management consisted of a combination of antibiotics and low-molecular-weight heparin (n = 16) or surgical removal (n = 2). In one case, no treatment was instituted. One patient was lost to follow-up after partial resolution of the thrombus. Complete thrombus resolution occurred in 18 patients, 9 with negative blood cultures and 9 with positive blood cultures. It took longer for resolution of thrombi associated with positive blood cultures than for sterile thrombi. No patient had evidence of thrombus embolization. From these data we concluded that the natural history of cardiac thrombi is resolution. Infected thrombi require more prolonged therapy. Surgery is seldom required and thrombolytics are not usually necessary for clot resolution.
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Affiliation(s)
- Edgard A Bendaly
- Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
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Kieboom JK, Siebelink MJ, Albers MJ. Heart valve donation in two small infants. Eur J Pediatr 2006; 165:498-9. [PMID: 16602000 DOI: 10.1007/s00431-006-0096-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2005] [Accepted: 01/24/2006] [Indexed: 11/30/2022]
Affiliation(s)
- Joke K Kieboom
- Department of Pediatrics, Beatrix Children's Hospital, University Medical Center Groningen, P.O. Box 30.001, 9700 RB Groningen, The Netherlands.
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