How to Cite
Abstract
A serious complication of cancer in children is venous thromboembolism (VTE). One of the main reasons for its development, in addition to the most malignant neoplasm, is the presence of a central venous catheter. Evolved VTE in children is usually treated with "classic" anticoagulants: unfractionated heparin, low molecular weight heparins, and vitamin K antagonists (VKAs). However, their use is associated with many problems: daily injections (for heparins), drug-drug interactions and the need to adjust the dose according to dietary vitamin K (for VKAs), close regular monitoring to maintain target therapeutic levels. These features of treatment are more burdensome in children than in adults. Switching to therapy with direct-acting oral anticoagulants could greatly simplify the management of pediatric patients with VTE. This scientific paper presents and analyzes the main results of a large clinical trial EINSTEIN-Junior, the purpose of which was to compare the efficacy and safety of rivaroxaban and standard anticoagulants in children with venous thromboembolism. The paper also provides arguments that suggest the efficacy and safety of using rivaroxaban in children with cancer.
References
Athale U, Siciliano S, Thabane L, et al. Epidemiology and clinical risk factors predisposing to thromboembolism in children with cancer. Pediatr Blood Cancer. 2008;51(6):792–7. doi:10.1002/pbc.21734.
Pelland-Marcotte MC, Tucker C, Klaassen A, et al. Outcomes and risk factors of massive and submassive pulmonary embolism in children: a retrospective cohort study. Lancet Haematol. 2019;6:e144-53. doi:10.1016/S2352-3026(18)30224-2.
Piovesan D, Attard C, Monagle P, et al. Epidemiology of venous thrombosis in children with cancer. Thromb Haemost. 2014;111(06):1015–21. doi:10.1160/TH13-10-0827.
Жарков П.А., Румянцев А.Г., Новичкова Г.А. Венозные тромбозы у детей со злокачественными новообразованиями (обзор литературы). Российский журнал детской гематологии и онкологии. 2015;2(1):66–74 [Zharkov PA, Rumyantsev AG, Novichkova GA. Venous thromboembolism in children with cancer. Rossiyskiy zhurnal detskoy gematologii i onkologii. Russian Journal of Pediatric Hematology and Oncology. 2015;2(1):66–74 (In Russ.)]. doi:10.17650/2311-1267-2015-1-66-74.
Male C, Monagle P, Albisetti M, et al. Direct oral anticoagulants: overcoming the challenges of managing venous thromboembolism in children. J Pediatr. 2022;240:14-23. doi:10.1016/j.jpeds.2021.09.025.
O’Brien SH, Candrilli SD. In the absence of a central venous catheter, risk of venous thromboembolism is low in critically injured children, adolescents, and young adults: evidence from the National Trauma Data Bank. Pediatr Crit Care Med. 2011;12:2516. doi:10.1097/PCC.0b013e3181f36bd9.
Monagle P, Adams M, Mahoney M, et al. Outcome of pediatric thromboembolic disease: a report from the Canadian Childhood Thrombophilia Registry. Pediatr Res. 2000;47:7636. doi:10.1203/00006450-200006000-00013.
Monagle P, Chan AKC, Goldenberg NA, et al. 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. 2012;141(2 Suppl):e737Se801S. doi:10.1378/chest.11-2308.
Chandarajoti K, Liu J, Pawlinski R. The design and synthesis of new synthetic low-molecular-weight heparins. J Thromb Haemost. 2016;14:113545. doi:10.1111/jth.13312.
Ko RH, Michieli C, Lira JL, et al. FondaKIDS II: long-term followup data of children receiving fondaparinux for treatment of venous thromboembolic events. Thromb Res. 2014;134:6437. doi:10.1016/j.thromres.2014.07.026.
O’Brien SH, Yee DL, Lira J, et al. UNBLOCK: an open-label, dose-finding, pharmacokinetic and safety study of bivalirudin in children with deep vein thrombosis. J Thromb Haemost. 2015;13:161522. doi:10.1111/jth.13057.
Ansell J, Hirsh J, Poller L, et al. The pharmacology and management of the vitamin K antagonists: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004;126(3 Suppl):204S33S. doi:10.1378/chest.126.3_suppl.204S.
Raskob GE, Büller HR, Segers A. Edoxaban for cancer-associated venous thromboembolism. N Engl J Med. 2018;379(1):9596. doi:10.1056/NEJMc1806646.
Young AM, Marshall A, Thirlwall J, et al. Comparison of an oral factor Xa inhibitor with low molecular weight heparin in patients with cancer with venous thromboembolism: results of a randomized trial (SELECT-D). J Clin Oncol. 2018;36(20):20172023. doi:10.1200/JCO.2018.78.8034.
McBane RD 2nd, Wysokinski WE, Le-Rademacher JG, et al. Apixaban and dalteparin in active malignancy-associated venous thromboembolism: The ADAM VTE trial. J Thromb Haemost. 2020;18(2):41121. doi:10.1111/jth.14662.
Verso M, Munoz A, Bauersachs R, et al. Effects of concomitant administration of anticancer agents and apixaban or dalteparin on recurrence and bleeding in patients with cancer-associated venous thromboembolism. Eur J Cancer. 2021;148:371381. doi:10.1016/j.ejca.2021.02.026.
Giustozzi M, Agnelli G, Del Toro-Cervera J, et al. Direct oral anticoagulants for the treatment of acute venous thromboembolism associated with cancer: a systematic review and meta-analysis. Thromb Haemost. 2020;120(7):11281136. doi:10.1055/s-0040-1712098.
Moik F, Posch F, Zielinski C, et al. Direct oral anticoagulants compared to low‐molecular‐weight heparin for the treatment of cancer‐associated thrombosis: Updated systematic review and meta‐analysis of randomized controlled trials. Res Pract Thromb Haemost. 2020;00:112. doi:10.1002/rth2.12359.
Mulder FI, Bosch FTM, Young AM, et al. Direct oral anticoagulants for treatment of cancer-associated venous thromboembolism: A systematic review and meta-analysis. Blood. 2020;136(12):14331441. doi:10.1182/blood.2020005819.
Attard C, Monagle P, Kubitza D, et al. The in vitro anticoagulant effect of rivaroxaban in children. Thromb Res. 2012;130:8047. doi:10.1016/j.thromres.2012.07.009.
Attard C, Monagle P, Kubitza D, et al. The in-vitro anticoagulant effect of rivaroxaban in neonates. Blood Coagul Fibrinolysis. 2014;25:23740. doi:10.1097/MBC.0000000000000033.
Willmann S, Becker C, Burghaus R, et al. Development of a paediatric population-based model of the pharmacokinetics of rivaroxaban. Clin Pharmacokinet. 2014;53:89102. doi:10.1007/s40262-013-0090-5.
Kubitza D, Willmann S, Becka M, et al. Exploratory evaluation of pharmacodynamics, pharmacokinetics and safety of rivaroxaban in children and adolescents: an EINSTEIN-Jr phase I study. Thromb J. 2018;16:31. doi:10.1186/s12959-018-0186-0.
Willmann S, Thelen K, Kubitza D, et al. Pharmacokinetics of rivaroxaban in children using physiologically based and population pharmacokinetic modelling: an EINSTEIN-Jr phase I study. Thromb J. 2018;16:32. doi:10.1186/s12959-018-0185-1.
Monagle P, Lensing AWA, Thelen K, et al. Bodyweight-adjusted rivaroxaban for children with venous thromboembolism (EINSTEIN-Jr): results from three multicentre, single-arm, phase 2 studies. Lancet Haematol. 2019;6:e5009. doi:10.1016/S2352-3026(19)30161-9.
Male C, Lensing AWA, Palumbo JS, et al. Rivaroxaban compared with standard anticoagulants for the treatment of acute venous thromboembolism in children: a randomised, controlled, phase 3 trial. Lancet Haematol. 2020;7:e1827. doi:10.1016/S2352-3026(19)30219-4.
Young G, Lensing AWA, Monagle P, et al. Rivaroxaban for treatment of pediatric venous thromboembolism. An EINSTEIN-Jr phase 3 dose-exposure-response evaluation. J Thromb Haemost. 2020;18:167285. doi:10.1111/jth.14813.
Prandoni P, Lensing AW, Piccioli A, et al. Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood. 2002;100(10):34848. doi:10.1182/blood-2002-01-0108.
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
© АННМО «Вопросы онкологии», Copyright (c) 2023