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Semin Thromb Hemost 2021; 47(06): 631-642
DOI: 10.1055/s-0041-1722847
Review Article

Venous Thromboembolism among Critically Ill Children: A Narrative Review

Anthony A. Sochet
1   Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
2   Division of Pediatric Critical Care Medicine, Department of Medicine, Johns Hopkins All Children's Hospital, St. Petersburg, Florida
3   Institute for Clinical and Translational Research, Johns Hopkins All Children's Hospital, St. Petersburg, Florida
,
Amy Kiskaddon
3   Institute for Clinical and Translational Research, Johns Hopkins All Children's Hospital, St. Petersburg, Florida
4   Department of Pharmacy, Johns Hopkins All Children's Hospital, St. Petersburg, Florida
,
Marisol Betensky
3   Institute for Clinical and Translational Research, Johns Hopkins All Children's Hospital, St. Petersburg, Florida
5   Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland
6   Thrombosis Program, Johns Hopkins All Children's Cancer and Blood Disorder Institute, Johns Hopkins All Children's Hospital, St. Petersburg, Florida
,
Neil Goldenberg
3   Institute for Clinical and Translational Research, Johns Hopkins All Children's Hospital, St. Petersburg, Florida
5   Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland
6   Thrombosis Program, Johns Hopkins All Children's Cancer and Blood Disorder Institute, Johns Hopkins All Children's Hospital, St. Petersburg, Florida
7   Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
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Abstract

Venous thromboembolism (VTE) is a leading cause of morbidity and mortality among hospitalized patients, including children. In recent years, it has become clear that hospitalization and critical illness bestow an increased VTE risk in pediatrics and relate to mortality and life-limiting comorbidities. For critically ill children, reported rates of VTE vary by study sampling techniques, presence of inherited or acquired thrombophilia, acute and chronic immobility, underlying illness prompting hospitalization, and clinical factors related to illness severity such as central venous catheterization, length of stay, mechanical ventilation, and patient age. Accordingly, critically ill children with new signs of venous congestion, acute inflammation, or unexplained acute organ dysfunction should be routinely evaluated for VTE. This narrative review summarizes recent and historical literature regarding risk factors, prevention, presentation, treatment, and outcomes of VTE in critically ill children. In addition, we identify knowledge gaps and priorities for future collaborative research on this vital condition. Special attention is given to the clinical trial opportunities, challenges, and ongoing efforts in thromboprophylaxis in critically ill children, including those hospitalized for disease related to novel coronavirus (COVID-19) and multisystem inflammatory disease in children.

Keywords

hospital-acquired VTE - pediatrics - critical care medicine - pediatric intensive care unit - thromboprophylaxis


Publication History

Article published online:
31 May 2021

© 2021. Thieme. All rights reserved.

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  • References

  • 1 Children's Hospitals' Association Solutions for Patient Safety. Our results: venous thromboembolism even rate. Accessed September 1, 2020 at: https://www.solutionsforpatientsafety.org/our-results/
    Google Scholar
  • 2 Sandoval JA, Sheehan MP, Stonerock CE, Shafique S, Rescorla FJ, Dalsing MC. Incidence, risk factors, and treatment patterns for deep venous thrombosis in hospitalized children: an increasing population at risk. J Vasc Surg 2008; 47 (04) 837-843
    CrossrefPubMedGoogle Scholar
  • 3 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
    CrossrefPubMedGoogle Scholar
  • 4 Tuckuviene R, Christensen AL, Helgestad J, Johnsen SP, Kristensen SR. Pediatric venous and arterial noncerebral thromboembolism in Denmark: a nationwide population-based study. J Pediatr 2011; 159 (04) 663-669
    CrossrefPubMedGoogle Scholar
  • 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
    CrossrefPubMedGoogle Scholar
  • 6 Hanson SJ, Punzalan RC, Christensen MA, Ghanayem NS, Kuhn EM, Havens PL. Incidence and risk factors for venous thromboembolism in critically ill children with cardiac disease. Pediatr Cardiol 2012; 33 (01) 103-108
    CrossrefPubMedGoogle Scholar
  • 7 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
    CrossrefPubMedGoogle Scholar
  • 8 Patel N, Petersen TL, Simpson PM, Feng M, Hanson SJ. Rates of venous thromboembolism and central line-associated bloodstream infections among types of central venous access devices in critically ill children. Crit Care Med 2020; 48 (09) 1340-1348
    CrossrefPubMedGoogle Scholar
  • 9 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
    CrossrefPubMedGoogle Scholar
  • 10 Atchison CM, Amankwah E, Wilhelm J. et al. Risk factors for hospital-associated venous thromboembolism in critically ill children following cardiothoracic surgery or therapeutic cardiac catheterisation. Cardiol Young 2018; 28 (02) 234-242
    CrossrefPubMedGoogle Scholar
  • 11 Amankwah EK, Atchison CM, Arlikar S. et al. Risk factors for hospital-sssociated venous thromboembolism in the neonatal intensive care unit. Thromb Res 2014; 134 (02) 305-309
    CrossrefPubMedGoogle Scholar
  • 12 Tran M, Shein SL, Ji X, Ahuja SP. Identification of a “VTE-rich” population in pediatrics - critically ill children with central venous catheters. Thromb Res 2018; 161: 73-77
    CrossrefPubMedGoogle Scholar
  • 13 Yen J, Van Arendonk KJ, Streiff MB. et al. Risk factors for venous thromboembolism in pediatric trauma patients and validation of a novel scoring system: the risk of clots in kids with trauma score. Pediatr Crit Care Med 2016; 17 (05) 391-399
    CrossrefPubMedGoogle Scholar
  • 14 Kim SJ, Sabharwal S. Risk factors for venous thromboembolism in hospitalized children and adolescents: a systemic review and pooled analysis. J Pediatr Orthop B 2014; 23 (04) 389-393
    CrossrefPubMedGoogle Scholar
  • 15 Mahajerin A, Jaffray J, Branchford B. et al. Comparative validation study of risk assessment models for pediatric hospital-acquired venous thromboembolism. J Thromb Haemost 2020; 18 (03) 633-641
    CrossrefPubMedGoogle Scholar
  • 16 Qaseem A, Chou R, Humphrey LL, Starkey M, Shekelle P. Clinical Guidelines Committee of the American College of Physicians. Venous thromboembolism prophylaxis in hospitalized patients: a clinical practice guideline from the American College of Physicians. Ann Intern Med 2011; 155 (09) 625-632
    CrossrefPubMedGoogle Scholar
  • 17 Thériault T, Touchette M, Goupil V, Echenberg D, Lanthier L. Thromboprophylaxis adherence to the ninth edition of American college of chest physicians antithrombotic guidelines in a tertiary care centre: a cross-sectional study. J Eval Clin Pract 2016; 22 (06) 952-957
    CrossrefPubMedGoogle Scholar
  • 18 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
    CrossrefPubMedGoogle Scholar
  • 19 Bigelow AM, Flynn-O'Brien KT, Simpson PM, Dasgupta M, Hanson SJ. Multicenter review of current practices associated with venous thromboembolism prophylaxis in pediatric patients after trauma. Pediatr Crit Care Med 2018; 19 (09) e448-e454
    CrossrefPubMedGoogle Scholar
  • 20 Faustino EV, Patel S, Thiagarajan RR, Cook DJ, Northrup V, Randolph AG. Survey of pharmacologic thromboprophylaxis in critically ill children. Crit Care Med 2011; 39 (07) 1773-1778
    CrossrefPubMedGoogle Scholar
  • 21 Jaffray J, Mahajerin A, Young G. et al. A multi-institutional registry of pediatric hospital-acquired thrombosis cases: The Children's Hospital-Acquired Thrombosis (CHAT) project. Thromb Res 2018; 161: 67-72
    CrossrefPubMedGoogle Scholar
  • 22 Goldenberg NA, Abshire T, Blatchford PJ. et al; Kids-DOTT Trial Investigators. Multicenter randomized controlled trial on Duration of Therapy for Thrombosis in Children and Young Adults (the Kids-DOTT trial): pilot/feasibility phase findings. J Thromb Haemost 2015; 13 (09) 1597-1605
    CrossrefPubMedGoogle Scholar
  • 23 Kuhle S, Koloshuk B, Marzinotto V. et al. A cross-sectional study evaluating post-thrombotic syndrome in children. Thromb Res 2003; 111 (4–5): 227-233
    CrossrefPubMedGoogle Scholar
  • 24 Newall F, Wallace T, Crock C. et al. Venous thromboembolic disease: a single-centre case series study. J Paediatr Child Health 2006; 42 (12) 803-807
    CrossrefPubMedGoogle Scholar
  • 25 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
    CrossrefPubMedGoogle Scholar
  • 26 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
    CrossrefPubMedGoogle Scholar
  • 27 Revel-Vilk S, Brandão LR, Journeycake J. et al; Perinatal And Paediatric Haemostasis Subcommittee Of The Scientific And Standardization Committee Of The International Society On Thrombosis And Haemostasis. Standardization of post-thrombotic syndrome definition and outcome assessment following upper venous system thrombosis in pediatric practice. J Thromb Haemost 2012; 10 (10) 2182-2185
    CrossrefPubMedGoogle Scholar
  • 28 Goldenberg NA, Brandão L, Journeycake J. et al; Perinatal And Paediatric Haemostasis Subcommittee Of The Scientific And Standardization Committee Of The International Society On Thrombosis And Haemostasis. Definition of post-thrombotic syndrome following lower extremity deep venous thrombosis and standardization of outcome measurement in pediatric clinical investigations. J Thromb Haemost 2012; 10 (03) 477-480
    CrossrefPubMedGoogle Scholar
  • 29 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
    CrossrefPubMedGoogle Scholar
  • 30 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
    PubMedGoogle Scholar
  • 31 Carpenter SL, Goldman J, Sherman AK. et al. Clinical variables and Staphylococcus aureus virulence factors associated with venous thromboembolism in children. Thromb Res 2016; 138: 69-73
    CrossrefPubMedGoogle Scholar
  • 32 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
    CrossrefPubMedGoogle Scholar
  • 33 Rajpurkar M, Huang YV, Raffini L. Additional analysis of pediatric pulmonary embolism using the Pediatric Health Information System database. Blood Adv 2019; 3 (17) 2604-2607
    CrossrefPubMedGoogle Scholar
  • 34 Berfelo FJ, Kersbergen KJ, van Ommen CH. et al. Neonatal cerebral sinovenous thrombosis from symptom to outcome. Stroke 2010; 41 (07) 1382-1388
    CrossrefPubMedGoogle Scholar
  • 35 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
    CrossrefPubMedGoogle Scholar
  • 36 Faustino EV, Spinella PC, Li S. et al. Incidence and acute complications of asymptomatic central venous catheter-related deep venous thrombosis in critically ill children. J Pediatr 2013; 162 (02) 387-391
    CrossrefPubMedGoogle Scholar
  • 37 Biss TT, Brandão LR, Kahr WH, Chan AK, Williams S. Clinical features and outcome of pulmonary embolism in children. Br J Haematol 2008; 142 (05) 808-818
    CrossrefPubMedGoogle Scholar
  • 38 Sharathkumar AA, Biss T, Kulkarni K. et al; SSC Subcommittee on Pediatrics and Neonatal T&H of the ISTH. Epidemiology and outcomes of clinically unsuspected venous thromboembolism in children: a systematic review. J Thromb Haemost 2020; 18 (05) 1100-1112
    CrossrefPubMedGoogle Scholar
  • 39 Faustino EVS, Shabanova V, Pinto MG. et al; THrombosis Epidemiology in Ill Adolescents (THEIA) Study Investigators. Epidemiology of lower extremity deep venous thrombosis in critically ill adolescents. J Pediatr 2018; 201: 176.e2-183.e2
    PubMedGoogle Scholar
  • 40 Jones S, Monagle P, Newall F. Do asymptomatic clots in children matter?. Thromb Res 2020; 189: 24-34
    CrossrefPubMedGoogle Scholar
  • 41 Sharathkumar AA, Mahajerin A, Heidt L. et al. Risk-prediction tool for identifying hospitalized children with a predisposition for development of venous thromboembolism: Peds-Clot clinical Decision Rule. J Thromb Haemost 2012; 10 (07) 1326-1334
    CrossrefPubMedGoogle Scholar
  • 42 Branchford BR, Mourani P, Bajaj L, Manco-Johnson M, Wang M, Goldenberg NA. Risk factors for in-hospital venous thromboembolism in children: a case-control study employing diagnostic validation. Haematologica 2012; 97 (04) 509-515
    CrossrefPubMedGoogle Scholar
  • 43 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
    CrossrefPubMedGoogle Scholar
  • 44 Kanin M, Young G. Incidence of thrombosis in children with tunneled central venous access devices versus peripherally inserted central catheters (PICCs). Thromb Res 2013; 132 (05) 527-530
    CrossrefPubMedGoogle Scholar
  • 45 Östlund Å, Fläring U, Norberg Å. et al. Incidence of and risk factors for venous thrombosis in children with percutaneous non-tunnelled central venous catheters. [published correction appears in Br J Anaesth. 2019 Dec;123(6):918] Br J Anaesth 2019; 123 (03) 316-324
    CrossrefPubMedGoogle Scholar
  • 46 Steen EH, Lasa JJ, Nguyen TC, Keswani SG, Checchia PA, Anders MM. Central venous catheter-related deep vein thrombosis in the pediatric cardiac intensive care unit. J Surg Res 2019; 241: 149-159
    CrossrefPubMedGoogle Scholar
  • 47 Chopra V, Anand S, Hickner A. et al. Risk of venous thromboembolism associated with peripherally inserted central catheters: a systematic review and meta-analysis. Lancet 2013; 382 (9889): 311-325
    CrossrefPubMedGoogle Scholar
  • 48 Gray BW, Gonzalez R, Warrier KS. et al. Characterization of central venous catheter-associated deep venous thrombosis in infants. J Pediatr Surg 2012; 47 (06) 1159-1166
    CrossrefPubMedGoogle Scholar
  • 49 Jaffray J, Witmer C, O'Brien SH. et al. Peripherally inserted central catheters lead to a high risk of venous thromboembolism in children. Blood 2020; 135 (03) 220-226
    CrossrefPubMedGoogle Scholar
  • 50 Andrew M. Developmental hemostasis: relevance to thromboembolic complications in pediatric patients. Thromb Haemost 1995; 74 (01) 415-425
    Article in Thieme ConnectPubMedGoogle Scholar
  • 51 Appel IM, Grimminck B, Geerts J, Stigter R, Cnossen MH, Beishuizen A. Age dependency of coagulation parameters during childhood and puberty. J Thromb Haemost 2012; 10 (11) 2254-2263
    CrossrefPubMedGoogle Scholar
  • 52 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. Thromb Haemost 2016; 116 (01) 9-16
    Article in Thieme ConnectPubMedGoogle Scholar
  • 53 McCafferty C, Busuttil-Crellin X, Cai T, Monagle P, Goldenberg NA, Ignjatovic V. Plasma proteomic analysis reveals age-specific changes in platelet- and endothelial cell-derived proteins and regulators of plasma coagulation and fibrinolysis. J Pediatr 2020; 221S: S29-S36
    CrossrefPubMedGoogle Scholar
  • 54 Haley KM, Recht M, McCarty OJ. Neonatal platelets: mediators of primary hemostasis in the developing hemostatic system. Pediatr Res 2014; 76 (03) 230-237
    CrossrefPubMedGoogle Scholar
  • 55 Strauss T, Sidlik-Muskatel R, Kenet G. Developmental hemostasis: primary hemostasis and evaluation of platelet function in neonates. Semin Fetal Neonatal Med 2011; 16 (06) 301-304
    CrossrefPubMedGoogle Scholar
  • 56 Li J, Lai X, Yan C. et al. Age-associated developmental changes in the activated partial thromboplastin time (APTT) and causes of prolonged APTT values in healthy Chinese children. Clin Chem Lab Med 2009; 47 (12) 1531-1537
    PubMedGoogle Scholar
  • 57 Malbora B, Bilaloglu E. Lupus anticoagulant positivity in pediatric patients with prolonged activated partial thromboplastin time: a single-center experience and review of literature. Pediatr Hematol Oncol 2015; 32 (07) 495-504
    CrossrefPubMedGoogle Scholar
  • 58 Allen CJ, Murray CR, Meizoso JP. et al. Risk factors for venous thromboembolism after pediatric trauma. J Pediatr Surg 2016; 51 (01) 168-171
    CrossrefPubMedGoogle Scholar
  • 59 Connelly CR, Laird A, Watters JM. Predicting venous thromboembolism in pediatric trauma patients-reply. JAMA Surg 2016; 151 (09) 882
    CrossrefPubMedGoogle Scholar
  • 60 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 (03) 251-256
    CrossrefPubMedGoogle Scholar
  • 61 Takemoto CM, Sohi S, Desai K. et al. Hospital-associated venous thromboembolism in children: incidence and clinical characteristics. J Pediatr 2014; 164 (02) 332-338
    CrossrefPubMedGoogle Scholar
  • 62 Normann S, de Veber G, Fobker M. et al. Role of endogenous testosterone concentration in pediatric stroke. Ann Neurol 2009; 66 (06) 754-758
    CrossrefPubMedGoogle Scholar
  • 63 Stokes S, Breheny P, Radulescu A, Radulescu VC. Impact of obesity on the risk of venous thromboembolism in an inpatient pediatric population. Pediatr Hematol Oncol 2014; 31 (05) 475-480
    CrossrefPubMedGoogle Scholar
  • 64 Ahn JJ, Merguerian PA, Shnorhavorian M. Incidence and risk factors associated with 30-day post-operative venous thromboembolism: a NSQIP-pediatric analysis. J Pediatr Urol 2018; 14 (04) 335.e1-335.e6
    CrossrefPubMedGoogle Scholar
  • 65 Ohmori H, Kanaoka Y, Yamasaki M, Takesue H, Sumimoto R. Prevalence and characteristic features of deep venous thrombosis in patients with severe motor and intellectual disabilities. Ann Vasc Dis 2018; 11 (03) 281-285
    CrossrefPubMedGoogle Scholar
  • 66 Ohmori H, Kada A, Nakamura M. et al. Deep vein thrombosis in severe motor and intellectual disabilities patients and its treatment by anticoagulants of warfarin versus edoxaban. Ann Vasc Dis 2019; 12 (03) 372-378
    CrossrefPubMedGoogle Scholar
  • 67 Manlhiot C, Menjak IB, Brandão LR. et al. Risk, clinical features, and outcomes of thrombosis associated with pediatric cardiac surgery. Circulation 2011; 124 (14) 1511-1519
    CrossrefPubMedGoogle Scholar
  • 68 Carpenter SL, Goldman J, Sherman AK. et al. Association of infections and venous thromboembolism in hospitalized children with nephrotic syndrome. Pediatr Nephrol 2019; 34 (02) 261-267
    CrossrefPubMedGoogle Scholar
  • 69 Braga AJ, Young AE. Preventing venous thrombosis in critically ill children: what is the right approach?. Paediatr Anaesth 2011; 21 (04) 435-440
    CrossrefPubMedGoogle Scholar
  • 70 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
    CrossrefPubMedGoogle Scholar
  • 71 Raffini L, Trimarchi T, Beliveau J, Davis D. Thromboprophylaxis in a pediatric hospital: a patient-safety and quality-improvement initiative. Pediatrics 2011; 127 (05) e1326-e1332
    CrossrefPubMedGoogle Scholar
  • 72 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. Hosp Pediatr 2015; 5 (12) 630-636
    CrossrefPubMedGoogle Scholar
  • 73 Meier KA, Clark E, Tarango C, Chima RS, Shaughnessy E. Venous thromboembolism in hospitalized adolescents: an approach to risk assessment and prophylaxis. Hosp Pediatr 2015; 5 (01) 44-51
    CrossrefPubMedGoogle Scholar
  • 74 Mahajerin A, Petty JK, Hanson SJ. et al. Prophylaxis against venous thromboembolism in pediatric trauma: a practice management guideline from the Eastern Association for the Surgery of Trauma and the Pediatric Trauma Society. J Trauma Acute Care Surg 2017; 82 (03) 627-636
    CrossrefPubMedGoogle Scholar
  • 75 Goldenberg NA, Sochet A, Albisetti M. et al; Pediatric/Neonatal Hemostasis and Thrombosis Subcommittee of the ISTH SSC. Consensus-based clinical recommendations and research priorities for anticoagulant thromboprophylaxis in children hospitalized for COVID-19-related illness. J Thromb Haemost 2020; 18 (11) 3099-3105
    CrossrefPubMedGoogle Scholar
  • 76 Badawy SM, Rychlik K, Sharathkumar AA. Current practice of pharmacological thromboprophylaxis for prevention of venous thromboembolism in hospitalized children: a survey of pediatric hemostasis and thrombosis experts in North America. J Pediatr Hematol Oncol 2016; 38 (04) 301-307
    CrossrefPubMedGoogle Scholar
  • 77 Amos LE, Silvey M, Hall M, Witmer CM, Carpenter SL. Primary thromboprophylaxis in hospitalized children: a multi-center retrospective analysis. Thromb Res 2019; 176: 1-7
    CrossrefPubMedGoogle Scholar
  • 78 Stem J, Christensen A, Davis D, Raffini L. Safety of prophylactic anticoagulation at a pediatric hospital. J Pediatr Hematol Oncol 2013; 35 (07) e287-e291
    CrossrefPubMedGoogle Scholar
  • 79 Onyeama SJ, Hanson SJ, Dasgupta M, Hoffmann RG, Faustino EV. Prophylaxis against Thrombosis Practice Study Investigators. Factors associated with continuous low-dose heparin infusion for central venous catheter patency in critically ill children worldwide. Pediatr Crit Care Med 2016; 17 (08) e352-e361
    CrossrefPubMedGoogle Scholar
  • 80 Pelland-Marcotte MC, Amiri N, Avila ML, Brandão LR. Low molecular weight heparin for prevention of central venous catheter-related thrombosis in children. Cochrane Database Syst Rev 2020; 6 (06) CD005982
    PubMedGoogle Scholar
  • 81 Shah PS, Shah N. Heparin-bonded catheters for prolonging the patency of central venous catheters in children. Cochrane Database Syst Rev 2014; (02) CD005983
    PubMedGoogle Scholar
  • 82 Porfidia A, Valeriani E, Pola R, Porreca E, Rutjes AWS, Di Nisio M. Venous thromboembolism in patients with COVID-19: Systematic review and meta-analysis. Thromb Res 2020; 196: 67-74
    CrossrefPubMedGoogle Scholar
  • 83 Zhang C, Shen L, Le KJ. et al. Incidence of venous thromboembolism in hospitalized coronavirus disease 2019 patients: a systematic review and meta-analysis. Front Cardiovasc Med 2020; 7: 151
    CrossrefPubMedGoogle Scholar
  • 84 Iba T, Levy JH, Levi M, Connors JM, Thachil J. Coagulopathy of coronavirus disease 2019. Crit Care Med 2020; 48 (09) 1358-1364
    CrossrefPubMedGoogle Scholar
  • 85 Tang N, Bai H, Chen X, Gong J, Li D, Sun Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost 2020; 18 (05) 1094-1099
    CrossrefPubMedGoogle Scholar
  • 86 Godfred-Cato S, Bryant B, Leung J. et al; California MIS-C Response Team. COVID-19-associated multisystem inflammatory syndrome in children - United States, March-July 2020. MMWR Morb Mortal Wkly Rep 2020; 69 (32) 1074-1080
    CrossrefPubMedGoogle Scholar
  • 87 Chao JY, Derespina KR, Herold BC. et al. Clinical characteristics and outcomes of hospitalized and critically ill children and adolescents with coronavirus disease 2019 at a tertiary care medical center in New York City. J Pediatr 2020; 223: 14.e2-19.e2
    PubMedGoogle Scholar
  • 88 Feldstein LR, Rose EB, Horwitz SM. et al; Overcoming COVID-19 Investigators, CDC COVID-19 Response Team. Multisystem inflammatory syndrome in U.S. Children and Adolescents. N Engl J Med 2020; 383 (04) 334-346
    CrossrefPubMedGoogle Scholar
  • 89 Kim L, Whitaker M, O'Halloran A. et al; COVID-NET Surveillance Team. Hospitalization rates and characteristics of children aged <18 years hospitalized with laboratory-confirmed COVID-19 - COVID-NET, 14 states, March 1-July 25, 2020. MMWR Morb Mortal Wkly Rep 2020; 69 (32) 1081-1088
    CrossrefPubMedGoogle Scholar
  • 90 Monagle P, Cuello CA, Augustine C. et al. American Society of Hematology 2018 Guidelines for management of venous thromboembolism: treatment of pediatric venous thromboembolism. Blood Adv 2018; 2 (22) 3292-3316
    CrossrefPubMedGoogle Scholar
  • 91 Newall F, Johnston L, Ignjatovic V, Monagle P. Unfractionated heparin therapy in infants and children. Pediatrics 2009; 123 (03) e510-e518
    CrossrefPubMedGoogle Scholar
  • 92 Sutor AH, Massicotte P, Leaker M, Andrew M. Heparin therapy in pediatric patients. Semin Thromb Hemost 1997; 23 (03) 303-319
    Article in Thieme ConnectPubMedGoogle Scholar
  • 93 Vandiver JW, Vondracek TG. Antifactor Xa levels versus activated partial thromboplastin time for monitoring unfractionated heparin. Pharmacotherapy 2012; 32 (06) 546-558
    CrossrefPubMedGoogle Scholar
  • 94 Klenner AF, Lubenow N, Raschke R, Greinacher A. Heparin-induced thrombocytopenia in children: 12 new cases and review of the literature. Thromb Haemost 2004; 91 (04) 719-724
    Article in Thieme ConnectPubMedGoogle Scholar
  • 95 Newall F, Barnes C, Ignjatovic V, Monagle P. Heparin-induced thrombocytopenia in children. J Paediatr Child Health 2003; 39 (04) 289-292
    CrossrefPubMedGoogle Scholar
  • 96 Law C, Raffini L. A guide to the use of anticoagulant drugs in children. Paediatr Drugs 2015; 17 (02) 105-114
    CrossrefPubMedGoogle Scholar
  • 97 Hirsh J, Levine MN. Low molecular weight heparin. Blood 1992; 79 (01) 1-17
    CrossrefPubMedGoogle Scholar
  • 98 Warkentin TE, Levine MN, Hirsh J. et al. Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin. N Engl J Med 1995; 332 (20) 1330-1335
    CrossrefPubMedGoogle Scholar
  • 99 Hasija S, Talwar S, Makhija N. et al. Randomized controlled trial of heparin versus bivalirudin anticoagulation in acyanotic children undergoing open heart surgery. J Cardiothorac Vasc Anesth 2018; 32 (06) 2633-2640
    CrossrefPubMedGoogle Scholar
  • 100 Ranucci M, Ballotta A, Kandil H. et al; Surgical and Clinical Outcome Research Group. Bivalirudin-based versus conventional heparin anticoagulation for postcardiotomy extracorporeal membrane oxygenation. Crit Care 2011; 15 (06) R275
    CrossrefPubMedGoogle Scholar
  • 101 Ryerson LM, Balutis KR, Granoski DA. et al. Prospective exploratory experience with bivalirudin anticoagulation in pediatric extracorporeal membrane oxygenation. Pediatr Crit Care Med 2020; 21 (11) 975-985
    CrossrefPubMedGoogle Scholar
  • 102 Machado DS, Tule M, Philip J, Wynn T, Lazarowicz M, Machuca T, Pipkin M, Alnuhaimat H, Ebraheem M, Peek G, Bleiweis M. Bivalirudin and alteplase for pulmonary embolism requiring veno-arterial extracorporeal membrane oxygenation in an adolescent. J Extra Corpor Technol 2020; 52 (04) 327-331
    CrossrefPubMedGoogle Scholar
  • 103 Snyder CW, Goldenberg NA, Nguyen ATH, Smithers CJ, Kays DW. A perioperative bivalirudin anticoagulation protocol for neonates with congenital diaphragmatic hernia on extracorporeal membrane oxygenation. Thromb Res 2020; 193: 198-203
    CrossrefPubMedGoogle Scholar
  • 104 Hamzah M, Jarden AM, Ezetendu C, Stewart R. Evaluation of bivalirudin as an alternative to heparin for systemic anticoagulation in pediatric extracorporeal membrane oxygenation. Pediatr Crit Care Med 2020; 21 (09) 827-834
    CrossrefPubMedGoogle Scholar
  • 105 Tarango C, Manco-Johnson MJ. Pediatric thrombolysis: a practical approach. Front Pediatr 2017; 5: 260
    CrossrefPubMedGoogle Scholar
  • 106 Goldenberg NA, Durham JD, Knapp-Clevenger R, Manco-Johnson MJ. A thrombolytic regimen for high-risk deep venous thrombosis may substantially reduce the risk of postthrombotic syndrome in children. Blood 2007; 110 (01) 45-53
    CrossrefPubMedGoogle Scholar
  • 107 Dandoy CE, Kukreja KU, Gruppo RA, Patel MN, Tarango C. Outcomes in children with deep vein thrombosis managed with percutaneous endovascular thrombolysis. Pediatr Radiol 2015; 45 (05) 719-726
    CrossrefPubMedGoogle Scholar
  • 108 Branchford BR, Betensky M, Goldenberg NA. Pediatric issues in thrombosis and hemostasis: the how and why of venous thromboembolism risk stratification in hospitalized children. Thromb Res 2018; 172: 190-193
    CrossrefPubMedGoogle Scholar