利伐沙班在儿童血栓栓塞性疾病中的研究进展

侯微, 冯鑫, 张金红, 殷述刚, 房德敏

中国药学杂志 ›› 2021, Vol. 56 ›› Issue (4) : 270-275.

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中国药学杂志 ›› 2021, Vol. 56 ›› Issue (4) : 270-275. DOI: 10.11669/cpj.2021.04.003
综述

利伐沙班在儿童血栓栓塞性疾病中的研究进展

  • 侯微a, 冯鑫a, 张金红a, 殷述刚b, 房德敏a*
作者信息 +

Research Progress of Rivaroxaban in Children with Thromboembolic Diseases

  • HOU Weia, FENG Xina, ZHANG Jin-honga, YIN Shu-gangb, FANG De-mina*
Author information +
文章历史 +

摘要

Xa因子抑制剂利伐沙班作为一种安全有效的口服抗凝剂,具有明确的药学特性,是当前多种成人血栓栓塞性疾病(thromboembolic disease,TED)的一线治疗药物。随着儿童抗凝用药的需求日趋增多,利伐沙班在儿科领域显示出巨大的潜力。笔者通过查阅近年来国内外相关指南、文献,总结0~18岁儿童TED的流行病学特点、凝血系统特点,综述利伐沙班在此类特殊人群中的药学特性、临床疗效及安全性相关研究,以期为儿科临床合理应用利伐沙班提供依据。

Abstract

Rivaroxaban, the first oral factor Xa inhibitor, is a safe and effective oral anticoagulant with definite pharmaceutical properties. It is the first-line treatment of various thromboembolic disease (TED) in adults. With the increasing demand for anticoagulants in children, rivaroxaban shows great potential in the field of pediatrics. This article collected the latest guidelines and literatures related to rivaroxaban in children aged 0-18, and summarized the epidemiological characteristics of TED, the characteristics of coagulation system, the research in pharmaceutical characteristics and clinical efficacy and safety, so as to provide a basis for the rational use of rivaroxaban in pediatrics.

关键词

利伐沙班 / 儿童 / 血栓栓塞性疾病

Key words

rivaroxaban / children / thromboembolic disease

引用本文

导出引用
侯微, 冯鑫, 张金红, 殷述刚, 房德敏. 利伐沙班在儿童血栓栓塞性疾病中的研究进展[J]. 中国药学杂志, 2021, 56(4): 270-275 https://doi.org/10.11669/cpj.2021.04.003
HOU Wei, FENG Xin, ZHANG Jin-hong, YIN Shu-gang, FANG De-min. Research Progress of Rivaroxaban in Children with Thromboembolic Diseases[J]. Chinese Pharmaceutical Journal, 2021, 56(4): 270-275 https://doi.org/10.11669/cpj.2021.04.003
中图分类号: R969.3   

参考文献

[1] BAUERSACHS R, BERKOWITZ S D, BRENNER B, et al. Oral rivaroxaban for symptomatic venous thromboembolism[J]. N Engl J Med, 2010, 363(26):2499-2510.
[2] PATEL M R, MAHAFFEY K W, GARG J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation[J]. N Engl J Med, 2011,365(10):883-891.
[3] BAYER A G. Xarelto® (rivaroxaban) Summary of Product Characteristics.[EB/OL]. European Medicines Agency,[2020-01-17]. https://www.ema.europa.eu/en/documents/product-information/xarelto-epar-product-information_en.pdf.
[4] TUCKUVIENE R, CHRISTENSEN A L, HELGESTAD J, et al. Pediatric venous and arterial noncerebral thromboembolism in Denmark: a nationwide population-based study[J]. J Pediatr, 2011, 159(4):663-669.
[5] RAFFINI L, HUANG Y S, WITMER C, et al. Dramatic increase in venous thromboembolism in children's hospitals in the United States from 2001 to 2007[J]. Pediatrics, 2009, 124(4):1001-1008.
[6] CARPENTER S L, RICHARDSON T, HALL M. Increasing rate of pulmonary embolism diagnosed in hospitalized children in the United States from 2001 to 2014[J]. Blood Adv, 2018, 2(12):1403-1408.
[7] GUPTA T, DELHI KUMAR C G, RAMESH KUMAR R, et al. Pediatric thrombotic events: incidence, clinical risk factors and outcome[J]. Indian J Pediatr, 2019, 86(3):241-244.
[8] TETSUHARA K, ISHIGURO A, MICHIHATA N, et al. Pediatric thromboembolism in Japan[J]. The Indian J Pediatr, 2016, 83(10):1077-1081.
[9] MONAGLE P, CHAN A K, GOLDENBERG N A, 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[J]. Chest, 2012, 141 (2 suppl): e737S-e801S.
[10] MONAGLE P, CUELLO C A, AUGUSTINE C, et al. American Society of Hematology 2018 Guidelines for management of venous thromboembolism: treatment of pediatric venous thromboembolism[J]. Blood Adv, 2018, 2(22):3292-3316.
[11] PENKOV D, TOMASI P, EICHLER I, et al. Pediatric medicine development: an overview and comparison of regulatory processes in the European Union and United States[J]. Ther Innov Regul Sci, 2017, 51(3):360-371.
[12] CNF1(2010). (中国国家处方集2010年版.化学药品与生物制品卷)[S]. 2010:6-10.
[13] ANDREW M, DAVID M, ADAMS M, et al. Venous thromboembolic complications (VTE) in children: first analyses of the Canadian Registry of VTE[J]. Blood, 1994, 83(5):1251-1257.
[14] VAN OMMEN C H, HEIJBOER H, BULLER H R, et al. Venous thromboembolism in childhood: a prospective two-year registry in the Netherlands[J]. J Pediatr, 2001, 139(5):676-681.
[15] SABAPATHY C A, DJOUONANG T N, KAHN S R, et al. Incidence trends and mortality from childhood venous thromboembolism: a population-based cohort study[J]. J Pediatr, 2016, 172:175-180.e1.
[16] MONAGLE P, NEWALL F, BARNES C, et al. Arterial thromboembolic disease: a single-centre case series study[J]. J Paediatr Child Health, 2008, 44(1-2):28-32.
[17] ANDREW M, PAES B, MILNER R, et al. Development of the human coagulation system in the full-term infant[J]. Blood, 1987, 70(1):165-172.
[18] ANDREW M, VEGH P, JOHNSTON M, et al. Maturation of the hemostatic system during childhood[J]. Blood, 1992, 80(8):1998-2005.
[19] APPEL I M, GRIMMINCK B, GEERTS J, et al. Age dependency of coagulation parameters during childhood and puberty[J]. J Thromb Haemost, 2012, 10(11):2254-2263.
[20] TOULON P, BERRUYER M, BRIONNE-FRANÇOIS M, et al. Age dependency for coagulation parameters in paediatric populations . Results of a multicentre study aimed at defining the age-specific reference ranges[J]. Thromb Haemost, 2016, 116(1):9-16.
[21] LIPPI G, FRANCHINI M, MONTAGNANA M, et al. Coagulation testing in pediatric patients: the young are not just miniature adults[J]. Semin Thromb Hemost, 2007, 33(8):816-820.
[22] WILLMANN S, BECKER C, BURGHAUS R, et al. Development of a paediatric population-based model of the pharmacokinetics of rivaroxaban[J]. Clin Pharmacokinet, 2014, 53(1):89-102.
[23] 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[J]. Thromb J, 2018, 16:32. doi: 10.1186/s12959-018-0185-1. eCollection 2018.
[24] ATTARD C, MONAGLE P, KUBITZA D, et al. The in vitro anticoagulant effect of rivaroxaban in children[J]. Thromb Res, 2012, 130(5):804-807.
[25] ATTARD C, MONAGLE P, KUBITZA D, et al. The in-vitro anticoagulant effect of rivaroxaban in neonates[J]. Blood Coagul Fibrin, 2014, 25(3):237-240.
[26] 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[J]. Thromb J, 2018, 16:31. doi: 10.1186/s12959-018-0186-0. eCollection 2018.
[27] MONAGLE P, LENSING A W A, THELEN K, et al. Bodyweight-adjusted rivaroxaban for children with venous thromboembolism (EINSTEIN-Jr): results from three multicentre, single-arm, phase 2 studies[J]. Lancet Haematol, 2019, 6(10):e500-e509.
[28] MARTINELLI I, BUCCIARELLI P, ARTONI A, et al. Anticoagulant treatment with rivaroxaban in severe protein S deficiency[J]. Pediatrics, 2013, 132(5):e1435-e1439.
[29] TRIPODI A, MARTINELLI, CHANTARANGKUL V, et al.Thrombin generation and other coagulation parameters in a patient with homozygous congenital protein S deficiency on treatment with rivaroxaban[J]. Int J Hematol, 2016, 103(2):165-172.
[30] MENON N, SARODE R, ZIA A. Rivaroxaban dose adjustment using thrombin generation in severe congenital protein C deficiency and warfarin-induced skin necrosis[J]. Blood Adv, 2018, 2(2):142-145.
[31] MARTI'NEZ-MARTI'NEZ I, NAVARRO-FERNA'NDEZ J, STERGAARD A, et al. Amelioration of the severity of heparin-binding antithrombin mutations by posttranslational mosaicism[J]. Blood, 2012, 120(4):900-904.
[32] VAN BRUWAENE L, HUISMAN A, URBANUS R T, et al. Heparin-resistant thrombosis due to homozygous antithrombin deficiency treated with rivaroxaban[J]. J Pediatr Hematol/Oncol, 2016, 38(8):658-660.
[33] SKRZYPCZYK P, MIZERSKA-WASIAK M, OFIARA A, et al. Pulmonary embolism in a girl with nephrotic syndrome and factor V Leiden-case report[J]. Pol Merkur Lekarski,2018,45(267):114-118.
[34] SAVINO S, BREEN K, HUNT B J. Rivaroxaban use in patients with antiphospholipid syndrome and previous venous thromboembolism[J]. Blood Coagul Fibrinolysis, 2015, 26(4):476-477.
[35] MACK J M, RICHTER G T, CRARY S E. Effectiveness and safety of treatment with direct oral anticoagulant rivaroxaban in patients with slow-flow vascular malformations: a case series[J]. Lymphat Res Biol, 2018, 16(3):278-281.
[36] MA J Y, ZHANG X, LI X F, et al. Thrombotic storm in a 4-year-old boy with a thrombus in the right atriu[J]. Chin J Pediatr(中华儿科杂志), 2018, 56(8):633-634.
[37] SHI Z M, ZHANG T Q, GUO W, et al. A case report of mycoplasma pneumonia-combined pulmonary thromboembolism in child[J]. Clin Focus(临床荟萃), 2019, 34(8):748-751.
[38] MALE C, LENSING A W A, PALUMBO J S, et al. Rivaroxaban compared with standard anticoagulants for the treatment of acute venous thromboembolism in children: a randomised, controlled, phase 3 trial[J]. Lancet Haematol, 2020, 7(1):e18-e27.
[39] LANGWIESER N, BERNLOCHNER I, WUSTROW I, et al. Combination of factor Xa inhibition and antiplatelet therapy after stenting in patients with iliofemoral post-thrombotic venous obstruction[J]. Phlebology, 2016, 31(6):430-437.
[40] IYENGAR A J, WINLAW D S, GALATI J C, et al. The Australia and New Zealand Fontan Registry: description and initial results from the first population-based Fontan registry[J]. Intern Med J, 2014, 44(2):148-155.
[41] PINA L M, DONG X, ZHANG L, et al. Rivaroxaban, a direct factor Xa inhibitor, versus acetylsalicylic acid as thromboprophylaxis in children post-Fontan procedure: rationale and design of a prospective, randomized trial (the universe study)[J]. Am Heart J, 2019, 213:97-104.
[42] DU X M, ZHU M T, JIAN L Y. Investigation and analysis of clinical application of rivaroxaban[J]. Chin Pharm J(中国药学杂志), 2019, 54(6):489-493.
[43] US Food and Drug Administration.2018 Biological License Application Approvals [EB/OL]. US Food and Drug Administration, [2019-01-13]. https://www.fda.gov/vaccines-blood-biologics/development-approval-process-cber/2018-biological-license-application-approvals.
[44] GOLDENBERG N A, ABSHIRE T, BLATCHFORD P J, et al. Multicenter randomized controlled trial on duration of therapy for thrombosis in children and young adults (the kids-DOTT trial): pilot/feasibility phase findings[J]. J Thromb Haemost, 2015, 13(9):1597-1605.
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