Antithrombotic Therapy |
| Antithrombotic
therapy for children is a rapidly evolving area of medical research and
practice due to the increasing recognition and diagnosis of
thromboembolic events (TEs) in pediatric populations. Unlike adults,
children experience TEs primarily as a consequence of severe illness or
medical interventions, such as central venous catheterization. This
distinct etiology necessitates tailored approaches to diagnosis,
treatment, and prevention. Pediatric TEs differ significantly from adult cases in terms of epidemiology, pathophysiology, and therapeutic implications. While the incidence of VTE in the general pediatric population remains low (0.07 to 0.14 per 10,000 children), hospitalized children face a much higher risk up to 1000-fold greaterdue to the widespread use of central venous access devices (CVADs) and other invasive procedures. Neonates and adolescents constitute the most vulnerable groups, reflecting distinct physiological and pathophysiological factors such as immature coagulation systems and pubertal hormonal changes. The pediatric coagulation system undergoes significant maturation during the first year of life, which alters the pharmacodynamics and pharmacokinetics of anticoagulant medications. For instance, younger children often require higher weight-based doses of anticoagulants, despite having lower levels of coagulation proteins. These differences pose unique challenges in drug selection, dosing, and monitoring. Historically, antithrombotic therapy in children has relied on unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), and vitamin K antagonists (VKAs). However, recent advances have introduced direct oral anticoagulants (DOACs) as a promising alternative due to their consistent pharmacokinetics, ease of administration, and reduced monitoring requirements. Clinical trials have demonstrated that DOACs, such as rivaroxaban and dabigatran, are as effective as standard anticoagulants while offering improved safety profiles. The American Society of Hematology (ASH) 2018 guidelines emphasize the use of anticoagulation in symptomatic VTE and stress the importance of individualized therapy based on the patient's clinical status and risk factors. For asymptomatic cases, the decision to treat remains contentious, reflecting the low certainty of evidence regarding the balance between risks and benefits. The recommendations also underline the need for multidisciplinary care involving pediatric hematologists to optimize treatment outcomes. Updated guidance from the International Society on Thrombosis and Haemostasis (ISTH) has refined outcome definitions for pediatric VTE clinical trials, introducing parameters like patient-important bleeding to standardize safety assessments. These developments aim to enhance the comparability and applicability of trial results. Despite significant progress, challenges remain. Many recommendations for pediatric antithrombotic therapy are extrapolated from adult studies due to the limited number of pediatric-specific trials. This reliance underscores the need for robust, age-appropriate research to address gaps in knowledge, particularly regarding long-term outcomes and the management of chronic conditions such as post-thrombotic syndrome. Meta-analyses and network comparisons have further clarified the efficacy and safety of various anticoagulants. For example, DOACs have shown non-inferiority to traditional agents in preventing recurrent TEs, with lower risks of major bleeding. However, concerns persist about their use in specific pediatric subgroups, such as neonates and critically ill children, highlighting the importance of cautious implementation based on individual risk profiles. Prophylactic anticoagulation remains a debated topic in pediatric care. Although standard in adult practice, its routine use in children is not widely endorsed due to the scarcity of high-quality evidence supporting its benefits. Studies investigating the role of prophylaxis in high-risk settings, such as CVAD-related thrombosis, have yielded mixed results, further complicating clinical decision-making. Emerging research continues to expand the therapeutic arsenal for pediatric TEs. The advent of age-specific formulations of DOACs, coupled with advances in imaging and biomarker technologies, holds promise for improving diagnostic precision and treatment efficacy. Moreover, ongoing trials are expected to address critical questions about optimal dosing, duration of therapy, and long-term safety. In conclusion, antithrombotic therapy in children has evolved significantly, driven by a growing understanding of pediatric hemostasis and advances in pharmacology. While traditional anticoagulants remain the cornerstone of treatment, DOACs represent a paradigm shift in managing pediatric TEs. Nevertheless, the field requires continued investment in research and collaboration to refine therapeutic strategies and ensure the best outcomes for young patients. References: 1- Monagle P, Chan AKC, Goldenberg NA, Ichord RN, Journeycake JM, Nowak-GŒttl U, Vesely SK: Antithrombotic therapy in neonates and children: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 141(2 Suppl):e737S-e801S, 2012 2- Young G. Anticoagulation Therapies in Children: Pediatr Clin North Am. 64(6):1257-1269, 2017 3- Monagle P, Cuello CA, Augustine C, Bonduel M, Brand?o LR, Capman T, Chan AKC, Hanson S, Male C, Meerpohl J, et al: American Society of Hematology 2018 Guidelines for management of venous thromboembolism: treatment of pediatric venous thromboembolism. Blood Adv. 2(22):3292-3316, 2018 4- Whitworth H, Amankwah EK, Betensky M, Castellucci LA, Cuker A, Goldenberg NA, Male C, Rinzler E, Zia A, Raffini L: Updated guidance for efficacy and safety outcomes for clinical trials in venous thromboembolism in children: Communication from the ISTH SSC Subcommittee on Pediatric and Neonatal Thrombosis and Hemostasis. J Thromb Haemost. 21(6):1666-1673, 2023 5- Gao H, Chen M, Huang Y, Liu H, Lin Y, Chen M: Efficacy and safety of antithrombotic therapy for preventing and treating pediatric thromboembolic disease: A systematic review. Sci Rep. 14(1):13378, 2024 6- Manco-Johnson MJ, Annam A, Schardt : Anticoagulation in Pediatric Patients. Tech Vasc Interv Radiol. 27(2):100958, 2024 |
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