Paul Monagle1, Anthony K C Chan2, Neil A Goldenberg3, Rebecca N Ichord4, Janna M Journeycake5, Ulrike Nowak-Göttl6, Sara K Vesely7. 1. Haematology Department, The Royal Children's Hospital, Department of Paediatrics, The University of Melbourne, Murdoch Children's Research Institute, Melbourne, VIC, Australia. 2. Department of Pediatrics, McMaster University, Hamilton, ON, Canada. 3. Department of Pediatrics, Section of Hematology/Oncology/Bone Marrow Transplantation and Mountain States Regional Hemophilia and Thrombosis Center, University of Colorado, Aurora, CO. 4. Department of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA. 5. Department of Pediatrics, University of Texas Southwestern Medical Center at Dallas, Dallas, TX. 6. Thrombosis and Hemostasis Unit, Institute of Clinical Chemistry, University Hospital Kiel, Kiel, Germany. 7. Department of Biostatistics and Epidemiology, University of Oklahoma Health Sciences Center, Oklahoma City, OK. Electronic address: sara-vesely@ouhsc.edu.
Abstract
BACKGROUND: Neonates and children differ from adults in physiology, pharmacologic responses to drugs, epidemiology, and long-term consequences of thrombosis. This guideline addresses optimal strategies for the management of thrombosis in neonates and children. METHODS: The methods of this guideline follow those described in the Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. RESULTS: We suggest that where possible, pediatric hematologists with experience in thromboembolism manage pediatric patients with thromboembolism (Grade 2C). When this is not possible, we suggest a combination of a neonatologist/pediatrician and adult hematologist supported by consultation with an experienced pediatric hematologist (Grade 2C). We suggest that therapeutic unfractionated heparin in children is titrated to achieve a target anti-Xa range of 0.35 to 0.7 units/mL or an activated partial thromboplastin time range that correlates to this anti-Xa range or to a protamine titration range of 0.2 to 0.4 units/mL (Grade 2C). For neonates and children receiving either daily or bid therapeutic low-molecular-weight heparin, we suggest that the drug be monitored to a target range of 0.5 to 1.0 units/mL in a sample taken 4 to 6 h after subcutaneous injection or, alternatively, 0.5 to 0.8 units/mL in a sample taken 2 to 6 h after subcutaneous injection (Grade 2C). CONCLUSIONS: The evidence supporting most recommendations for antithrombotic therapy in neonates and children remains weak. Studies addressing appropriate drug target ranges and monitoring requirements are urgently required in addition to site- and clinical situation-specific thrombosis management strategies.
BACKGROUND: Neonates and children differ from adults in physiology, pharmacologic responses to drugs, epidemiology, and long-term consequences of thrombosis. This guideline addresses optimal strategies for the management of thrombosis in neonates and children. METHODS: The methods of this guideline follow those described in the Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. RESULTS: We suggest that where possible, pediatric hematologists with experience in thromboembolism manage pediatric patients with thromboembolism (Grade 2C). When this is not possible, we suggest a combination of a neonatologist/pediatrician and adult hematologist supported by consultation with an experienced pediatric hematologist (Grade 2C). We suggest that therapeutic unfractionated heparin in children is titrated to achieve a target anti-Xa range of 0.35 to 0.7 units/mL or an activated partial thromboplastin time range that correlates to this anti-Xa range or to a protamine titration range of 0.2 to 0.4 units/mL (Grade 2C). For neonates and children receiving either daily or bid therapeutic low-molecular-weight heparin, we suggest that the drug be monitored to a target range of 0.5 to 1.0 units/mL in a sample taken 4 to 6 h after subcutaneous injection or, alternatively, 0.5 to 0.8 units/mL in a sample taken 2 to 6 h after subcutaneous injection (Grade 2C). CONCLUSIONS: The evidence supporting most recommendations for antithrombotic therapy in neonates and children remains weak. Studies addressing appropriate drug target ranges and monitoring requirements are urgently required in addition to site- and clinical situation-specific thrombosis management strategies.
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