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DOI: 10.1055/s-0042-1748151
Prophylaxis of Venous Thromboembolism in Children: A Systematic Review
Abstract
Venous thromboembolism (VTE) in children is a rare but serious event. Current guidance on pharmacological thromboprophylaxis in children is mostly based on adult studies and expert opinions. The aim of this systematic review was to examine under which conditions children (age ≤ 18 years) would benefit from pharmacological thromboprophylaxis with low molecular weight heparin or unfractionated heparin. Eligible studies included children, who did not receive pharmacological thromboprophylaxis as comparator, and VTE events were radiologically verified. MEDLINE and Embase were searched up to October 3, 2021. Ten studies were included presenting data for 976 children receiving pharmacological thromboprophylaxis. We divided the studies into three categories based on the population studied: children in the intensive care unit (n = 2), children with fractures and/or undergoing surgery (n = 5), and children with systemic disease (n = 3). A lower incidence of VTE was found when pharmacological thromboprophylaxis was used compared with no prophylaxis in children in intensive care unit with central venous catheter and mechanical ventilation (7/27 vs. 13/24), children in the intensive care unit admitted after trauma with a very high risk of VTE based on several risk factors (0/21 vs. 13/96), and children with acute lymphoblastic leukemia treated with L-asparaginase concomitant with steroid and presence of central venous catheter (0/82 vs. 8/121). Pharmacological thromboprophylaxis was not associated with an increased bleeding risk. In conclusion, pharmacological thromboprophylaxis in children is sparsely investigated. Only children with several risk factors for VTE are likely to benefit from pharmacological thromboprophylaxis.
Keywords
heparin - low molecular weight heparin - pediatric - thromboprophylaxis - venous thromboembolism* Shared first authorship: the authors contributed equally to the manuscript
Publication History
Article published online:
30 June 2022
© 2022. Thieme. All rights reserved.
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References
- 1 Witmer CM, Takemoto CM. Pediatric hospital acquired venous thromboembolism. Front Pediatr 2017; 5: 198
- 2 van Ommen CH, Heijboer H, Büller HR, Hirasing RA, Heijmans HS, Peters M. Venous thromboembolism in childhood: a prospective two-year registry in The Netherlands. J Pediatr 2001; 139 (05) 676-681
- 3 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 (06) 763-766
- 4 Goldenberg NA, Donadini MP, Kahn SR. et al. Post-thrombotic syndrome in children: a systematic review of frequency of occurrence, validity of outcome measures, and prognostic factors. Haematologica 2010; 95 (11) 1952-1959
- 5 Raffini L, Huang YS, Witmer C, Feudtner C. Dramatic increase in venous thromboembolism in children's hospitals in the United States from 2001 to 2007. Pediatrics 2009; 124 (04) 1001-1008
- 6 Wright JM, Watts RG. Venous thromboembolism in pediatric patients: epidemiologic data from a pediatric tertiary care center in Alabama. J Pediatr Hematol Oncol 2011; 33 (04) 261-264
- 7 Setty BA, O'Brien SH, Kerlin BA. Pediatric venous thromboembolism in the United States: a tertiary care complication of chronic diseases. Pediatr Blood Cancer 2012; 59 (02) 258-264
- 8 Male C, Lensing AWA, Palumbo JS. et al; EINSTEIN-Jr Phase 3 Investigators. Rivaroxaban compared with standard anticoagulants for the treatment of acute venous thromboembolism in children: a randomised, controlled, phase 3 trial. Lancet Haematol 2020; 7 (01) e18-e27
- 9 Carpenter SL, Richardson T, Hall M. Increasing rate of pulmonary embolism diagnosed in hospitalized children in the United States from 2001 to 2014. Blood Adv 2018; 2 (12) 1403-1408
- 10 Radulescu VC, D'Orazio JA. Venous Thromboembolic Disease in Children and Adolescents. 2017: 149-165
- 11 Kahn SR, Lim W, Dunn AS. et al. Prevention of VTE in nonsurgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141 (2, Suppl): e195S-e226S
- 12 Gould MK, Garcia DA, Wren SM. et al. Prevention of VTE in nonorthopedic surgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141 (2, Suppl): e227S-e277S
- 13 Falck-Ytter Y, Francis CW, Johanson NA. et al. Prevention of VTE in orthopedic surgery patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141 (2, Suppl): e278S-e325S
- 14 Andrew M, Paes B, Milner R. et al. Development of the human coagulation system in the full-term infant. Article Blood 1987; 70 (01) 165-172
- 15 Andrew M, Vegh P, Johnston M, Bowker J, Ofosu F, Mitchell L. Maturation of the hemostatic system during childhood. Blood 1992; 80 (08) 1998-2005
- 16 Stein PD, Kayali F, Olson RE. Incidence of venous thromboembolism in infants and children: data from the National Hospital Discharge Survey. J Pediatr 2004; 145 (04) 563-565
- 17 Andrew M, David M, Adams M. et al. Venous thromboembolic complications (VTE) in children: first analyses of the Canadian Registry of VTE. Blood 1994; 83 (05) 1251-1257
- 18 Tuckuviene R, Christensen AL, Helgestad J, Johnsen SP, Kristensen SR. Pediatric venous and arterial noncerebral thromboembolism in Denmark: a nationwide population-based study. Article J Pediatr 2011; 159 (04) 663-669
- 19 Naess IA, Christiansen SC, Romundstad P, Cannegieter SC, Rosendaal FR, Hammerstrøm J. Incidence and mortality of venous thrombosis: a population-based study. J Thromb Haemost 2007; 5 (04) 692-699
- 20 Connors JM. Thrombophilia testing and venous thrombosis. Review N Engl J Med 2017; 377 (12) 1177-1187
- 21 Chalmers E, Ganesen V, Liesner R. et al; British Committee for Standards in Haematology. Guideline on the investigation, management and prevention of venous thrombosis in children. Article Br J Haematol 2011; 154 (02) 196-207
- 22 Nowak-Göttl U, Bidlingmaier C, Krümpel A, Göttl L, Kenet G. Pharmacokinetics, efficacy, and safety of LMWHs in venous thrombosis and stroke in neonates, infants and children. Br J Pharmacol 2008; 153 (06) 1120-1127
- 23 PRISMA. Transparent reporting of systematic reviews and meta-analyses. February 2021 Accessed March 22, 2022 at: http://prisma-statement.org/PRISMAStatement/Checklist.aspx
- 24 National heart, lung and blood institute. Study Quality Assessment Tools. February 2021 Accessed March 22, 2022 at: https://www.nhlbi.nih.gov/health-topics/study-quality-assessment-tools
- 25 Leeper CM, Vissa M, Cooper JD, Malec LM, Gaines BA. Venous thromboembolism in pediatric trauma patients: ten-year experience and long-term follow-up in a tertiary care center. Article Pediatr Blood Cancer 2017;64(08):
- 26 Faustino EVS, Shabanova V, Raffini LJ. et al. Efficacy of early prophylaxis against catheter-associated thrombosis in critically ill children: a Bayesian phase 2b randomized clinical trial. Crit Care Med 2020; . (e-Pub ahead of Print) DOI: 10.1097/ccm.0000000000004784.
- 27 Massicotte P, Julian JA, Gent M. et al; PROTEKT Study Group. An open-label randomized controlled trial of low molecular weight heparin for the prevention of central venous line-related thrombotic complications in children: the PROTEKT trial. Thromb Res 2003; 109 (2-3): 101-108
- 28 Vorisek CN, Sleeper LA, Piekarski B. et al. High-dose heparin is associated with higher bleeding and thrombosis rates in pediatric patients following cardiac surgery. J Thorac Cardiovasc Surg 2019; 158 (04) 1199-1206
- 29 Kochai A, Cicekli O, Bayam L, Türker M, Sariyilmaz K, Erkorkmaz Ü. Is pharmacological anticoagulant prophylaxis necessary for adolescent idiopathic scoliosis surgery?. Medicine (Baltimore) 2019; 98 (29) e16552
- 30 Zeng XJ, Peng H. Prevention of thromboembolic complications after spine surgery by the use of low-molecular-weight heparin. Article World Neurosurg 2017; 104: 856-862
- 31 Greenwald LJ, Yost MT, Sponseller PD, Abdullah F, Ziegfeld SM, Ain MC. The role of clinically significant venous thromboembolism and thromboprophylaxis in pediatric patients with pelvic or femoral fractures. J Pediatr Orthop 2012; 32 (04) 357-361
- 32 Meister B, Kropshofer G, Klein-Franke A, Strasak AM, Hager J, Streif W. Comparison of low-molecular-weight heparin and antithrombin versus antithrombin alone for the prevention of symptomatic venous thromboembolism in children with acute lymphoblastic leukemia. Pediatr Blood Cancer 2008; 50 (02) 298-303
- 33 Elhasid R, Lanir N, Sharon R. et al. Prophylactic therapy with enoxaparin during L-asparaginase treatment in children with acute lymphoblastic leukemia. Article Blood Coagul Fibrinolysis 2001; 12 (05) 367-370
- 34 Murphy LD, Benneyworth BD, Moser EAS, Hege KM, Valentine KM, Mastropietro CW. Analysis of patient characteristics and risk factors for thrombosis after surgery for congenital heart disease. Pediatr Crit Care Med 2018; 19 (12) 1146-1152
- 35 Male C, Julian JA, Massicotte P, Gent M, Mitchell L. PROTEKT Study Group. Significant association with location of central venous line placement and risk of venous thrombosis in children. Thromb Haemost 2005; 94 (03) 516-521
- 36 Tullius BP, Athale U, van Ommen CH, Chan AKC, Palumbo JS, Balagtas JMS. Subcommittee on Hemostasis and Malignancy and the Subcommittee on Pediatric/Neonatal Thrombosis and Hemostasis. The identification of at-risk patients and prevention of venous thromboembolism in pediatric cancer: guidance from the SSC of the ISTH. Article J Thromb Haemost 2018; 16 (01) 175-180
- 37 Arlikar SJ, Atchison CM, Amankwah EK. et al. Development of a new risk score for hospital-associated venous thromboembolism in critically-ill children not undergoing cardiothoracic surgery. Thromb Res 2015; 136 (04) 717-722
- 38 Sibson KR, Biss TT, Furness CL. et al; British Society for Haematology. BSH Guideline: management of thrombotic and haemostatic issues in paediatric malignancy. Article Br J Haematol 2018; 180 (04) 511-525
- 39 Georgeades C, Van Arendonk K, Gourlay D. Venous thromboembolism prophylaxis after pediatric trauma. Pediatr Surg Int 2021; 37 (06) 679-694
- 40 Odent T, de Courtivron B, Gruel Y. Thrombotic risk in children undergoing orthopedic surgery. Orthop Traumatol Surg Res 2020; 106 (1S, 1s): S109-S114
- 41 Connelly CR, Laird A, Barton JS. et al. A clinical tool for the prediction of venous thromboembolism in pediatric trauma patients. JAMA Surg 2016; 151 (01) 50-57
- 42 Padhye K, El-Hawary R, Price V, Stevens S, Branchford B, Kulkarni K. Development of a perioperative venous thromboembolism prophylaxis algorithm for pediatric orthopedic surgical patients. Pediatr Hematol Oncol 2020; 37 (02) 109-118
- 43 Meier KA, Clark E, Tarango C, Chima RS, Shaughnessy E. Venous thromboembolism in hospitalized adolescents: an approach to risk assessment and prophylaxis. Review Hosp Pediatr 2015; 5 (01) 44-51
- 44 Raffini L, Trimarchi T, Beliveau J, Davis D. Thromboprophylaxis in a pediatric hospital: a patient-safety and quality-improvement initiative. Article Pediatrics 2011; 127 (05) e1326-e1332
- 45 Mahajerin A, Webber EC, Morris J, Taylor K, Saysana M. Development and implementation results of a venous thromboembolism prophylaxis guideline in a tertiary care pediatric hospital. Article Hosp Pediatr 2015; 5 (12) 630-636
- 46 Hanson SJ, Punzalan RC, Arca MJ. et al. Effectiveness of clinical guidelines for deep vein thrombosis prophylaxis in reducing the incidence of venous thromboembolism in critically ill children after trauma. J Trauma Acute Care Surg 2012; 72 (05) 1292-1297
- 47 Mahajerin A, Branchford BR, Amankwah EK. et al. Hospital-associated venous thromboembolism in pediatrics: a systematic review and meta-analysis of risk factors and risk-assessment models. Haematologica 2015; 100 (08) 1045-1050
- 48 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): e737S-e801S
- 49 Schoot RA, Kremer LC, van de Wetering MD, van Ommen CH. Systemic treatments for the prevention of venous thrombo-embolic events in paediatric cancer patients with tunnelled central venous catheters. Cochrane Database Syst Rev 2013; (09) CD009160
- 50 Pelland-Marcotte MC, Amiri N, Avila ML, Brandão LR. Low molecular weight heparin for prevention of central venous catheter-related thrombosis in children. Article Cochrane Database Syst Rev 2020; 6 (06) CD005982
- 51 Vidal E, Sharathkumar A, Glover J, Faustino EV. Central venous catheter-related thrombosis and thromboprophylaxis in children: a systematic review and meta-analysis. J Thromb Haemost 2014; 12 (07) 1096-1109
- 52 Higgerson RA, Lawson KA, Christie LM. et al; National Association of Children's Hospitals and Related Institution's Pediatric Intensive Care Unit FOCUS group. Incidence and risk factors associated with venous thrombotic events in pediatric intensive care unit patients. Pediatr Crit Care Med 2011; 12 (06) 628-634
- 53 Faustino EV, Hanson S, Spinella PC. et al; PROphylaxis against ThRombosis prACTice (PROTRACT) Study Investigators of the PALISI BloodNet. A multinational study of thromboprophylaxis practice in critically ill children. Crit Care Med 2014; 42 (05) 1232-1240
- 54 Hanson SJ, Faustino EV, Mahajerin A. et al. Recommendations for venous thromboembolism prophylaxis in pediatric trauma patients: a national, multidisciplinary consensus study. J Trauma Acute Care Surg 2016; 80 (05) 695-701
- 55 Giglia TM, Massicotte MP, Tweddell JS. et al; American Heart Association Congenital Heart Defects Committee of the Council on Cardiovascular Disease in the Young, Council on Cardiovascular and Stroke Nursing, Council on Epidemiology and Prevention, and Stroke Council. Prevention and treatment of thrombosis in pediatric and congenital heart disease: a scientific statement from the American Heart Association. Article Circulation 2013; 128 (24) 2622-2703