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Semin Thromb Hemost
DOI: 10.1055/a-2546-0126
Review Article

Anticoagulants in Children with Renal Impairment: A Narrative Review

Amy L. Kiskaddon
1   Division of Cardiology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland
2   Division of Hematology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland
3   Institute for Clinical and Translational Research, Johns Hopkins All Children's, St. Petersburg, Florida
4   Department of Pharmacy, Johns Hopkins All Children's Hospital, St. Petersburg, Florida
5   Heart Institute, Johns Hopkins All Children's Hospital, St. Petersburg, Florida
,
Daniel M. Witt
6   Department of Pharmacotherapy, University of Utah College of Pharmacy, Salt Lake City, Utah
,
Marisol Betensky
2   Division of Hematology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland
7   Cancer and Blood Disorders Institute, Johns Hopkins All Children's Hospital, St. Petersburg, Florida
,
Anthony A. Sochet
8   Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
9   Division of Pediatric Critical Care Medicine, Department of Medicine, Johns Hopkins All Children's Hospital, St. Petersburg, Florida
,
Amanda Memken
4   Department of Pharmacy, Johns Hopkins All Children's Hospital, St. Petersburg, Florida
,
Christoph Male
10   Department of Pediatrics, Medical University of Vienna, Vienna, Austria
,
Neil A. Goldenberg
2   Division of Hematology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland
3   Institute for Clinical and Translational Research, Johns Hopkins All Children's, St. Petersburg, Florida
7   Cancer and Blood Disorders Institute, Johns Hopkins All Children's Hospital, St. Petersburg, Florida
11   Division of Hematology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland
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Abstract

Venous thromboembolism is a common cause of morbidity and mortality in children with renal disease. To properly treat and prevent thromboembolism in this patient population, it is important to be familiar with the multitude of anticoagulant agents currently available. Many anticoagulant drugs undergo some extent of renal elimination. There are important considerations for the selection, dosing, and monitoring of anticoagulant drugs for patients with renal impairment due to various pharmacokinetic alterations that may occur. While there are data to help guide dosing and monitoring in adults, evidence regarding renal dose adjustment of many anticoagulant drugs in children are limited. For the clinician, anticoagulation management in children with renal impairment presents unique challenges. In addition to considering overall bleeding risk, the extent of renal impairment may vary by patient, making a one-size-fits-all approach to managing these patients difficult. These factors, combined with limited data, can make managing anticoagulation in children with renal impairment a challenge. Therefore, the focus of this review will be to describe the pharmacokinetics of the following anticoagulants in children with impaired renal function: unfractionated heparin, enoxaparin, dalteparin, rivaroxaban, apixaban, edoxaban, fondaparinux, bivalirudin, argatroban, dabigatran, and warfarin.

Keywords

anticoagulants - pediatric - renal impairment

Supplementary Material



Publication History

Received: 31 December 2024

Accepted: 24 February 2025

Article published online:
28 March 2025

© 2025. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
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  • References

  • 1 Wattanakit K, Cushman M. Chronic kidney disease and venous thromboembolism: epidemiology and mechanisms. Curr Opin Pulm Med 2009; 15 (05) 408-412
    CrossrefPubMedSearch in Google Scholar
  • 2 Szeps I, Östlund Å, Norberg Å, Fläring U, Andersson A. Thromboembolic complications of vascular catheters used for pediatric continuous renal replacement therapy: Prevalence in a single-center, retrospective cohort. Pediatr Crit Care Med 2021; 22 (08) 743-752
    CrossrefPubMedSearch in Google Scholar
  • 3 Virchow R. Thrombosis and embolie. In: Gesammelte Abhandlungen zur Wissenshaftlichen Medicin. Canton, MA: Science History Publications; 1856: 219-732
    Search in Google Scholar
  • 4 Mandel-Shorer N, Tzvi-Behr S, Harvey E, Revel-Vilk S. Central venous catheter-related venous thrombosis in children with end-stage renal disease undergoing hemodialysis. Thromb Res 2018; 172: 150-157
    CrossrefPubMedSearch in Google Scholar
  • 5 Ribic C, Crowther M. Thrombosis and anticoagulation in the setting of renal or liver disease. Hematology (Am Soc Hematol Educ Program) 2016; 2016 (01) 188-195
    CrossrefPubMedSearch in Google Scholar
  • 6 Thorevska N, Amoateng-Adjepong Y, Sabahi R. et al. Anticoagulation in hospitalized patients with renal insufficiency: a comparison of bleeding rates with unfractionated heparin vs enoxaparin. Chest 2004; 125 (03) 856-863
    CrossrefPubMedSearch in Google Scholar
  • 7 Kidney Disease: Improving Global Outcomes (KDIGO)Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney int Suppl 2012; 2: 1-138
    PubMedSearch in Google Scholar
  • 8 Colantonio DA, Kyriakopoulou L, Chan MK. et al. Closing the gaps in pediatric laboratory reference intervals: a CALIPER database of 40 biochemical markers in a healthy and multiethnic population of children. Clin Chem 2012; 58 (05) 854-868
    CrossrefPubMedSearch in Google Scholar
  • 9 Arant Jr BS. Developmental patterns of renal functional maturation compared in the human neonate. J Pediatr 1978; 92 (05) 705-712
    CrossrefPubMedSearch in Google Scholar
  • 10 Robillard JE, Guillery EN, Petershack JA. Renal function during fetal life. In: Barratt TM, Avner ED, Harmon WE. eds. Pediatric nephrology. 4th ed. Baltimore: Lippincott Williams & Wilkins; 1999: 21-37
    Search in Google Scholar
  • 11 Bendayan R. Renal drug transport: a review. Pharmacotherapy 1996; 16 (06) 971-985
    CrossrefPubMedSearch in Google Scholar
  • 12 Lea-Henry TN, Carland JE, Stocker SL, Sevastos J, Roberts DM. Clinical pharmacokinetics in kidney disease: Fundamental principles. Clin J Am Soc Nephrol 2018; 13 (07) 1085-1095
    CrossrefPubMedSearch in Google Scholar
  • 13 Sharathkumar AA. Current practice perspectives on the management of thrombosis in children with renal insufficiency: the results of a survey of pediatric hematologists in North America. Pediatr Blood Cancer 2008; 51 (05) 657-661
    CrossrefPubMedSearch in Google Scholar
  • 14 Jang SM, Infante S, Abdi Pour A. Drug dosing considerations in critically ill patients receiving continuous renal replacement therapy. Pharmacy (Basel) 2020; 8 (01) 18
    CrossrefPubMedSearch in Google Scholar
  • 15 Kanji S, Roger C, Taccone FS, Muller L. Practical considerations for individualizing drug dosing in critically ill adults receiving renal replacement therapy. Pharmacotherapy 2023; 43 (11) 1194-1205
    CrossrefPubMedSearch in Google Scholar
  • 16 Matzke GR, Aronoff GR, Atkinson Jr AJ. et al. Drug dosing consideration in patients with acute and chronic kidney disease-a clinical update from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2011; 80 (11) 1122-1137
    CrossrefPubMedSearch in Google Scholar
  • 17 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 (02) e737S-e801S
    CrossrefPubMedSearch in Google Scholar
  • 18 Rajani K, Goetzman BW, Wennberg RP, Turner E, Abildgaard C. Effect of heparinization of fluids infused through an umbilical artery catheter on catheter patency and frequency of complications. Pediatrics 1979; 63 (04) 552-556
    CrossrefPubMedSearch in Google Scholar
  • 19 Newall F, Johnston L, Ignjatovic V, Monagle P. Unfractionated heparin therapy in infants and children. Pediatrics 2009; 123 (03) e510-e518
    CrossrefPubMedSearch in Google Scholar
  • 20 Hanslik A, Kitzmüller E, Tran US. et al. Monitoring unfractionated heparin in children: a parallel-cohort randomized controlled trial comparing 2 dose protocols. Blood 2015; 126 (18) 2091-2097
    CrossrefPubMedSearch in Google Scholar
  • 21 Arachchillage DRJ, Kamani F, Deplano S, Banya W, Laffan M. Should we abandon the APTT for monitoring unfractionated heparin?. Thromb Res 2017; 157: 157-161
    CrossrefPubMedSearch in Google Scholar
  • 22 Tripodi A, Cohen H, Devreese KMJ. Lupus anticoagulant detection in anticoagulated patients. Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis. J Thromb Haemost 2020; 18 (07) 1569-1575
    CrossrefPubMedSearch in Google Scholar
  • 23 Hughes S, Szeki I, Nash MJ, Thachil J. Anticoagulation in chronic kidney disease patients-the practical aspects. Clin Kidney J 2014; 7 (05) 442-449
    CrossrefPubMedSearch in Google Scholar
  • 24 Shammas NW. Bivalirudin: pharmacology and clinical applications. Cardiovasc Drug Rev 2005; 23 (04) 345-360
    CrossrefPubMedSearch in Google Scholar
  • 25 O'Brien SH, Yee DL, Lira J, Goldenberg NA, Young G. UNBLOCK: an open-label, dose-finding, pharmacokinetic and safety study of bivalirudin in children with deep vein thrombosis. J Thromb Haemost 2015; 13 (09) 1615-1622
    CrossrefPubMedSearch in Google Scholar
  • 26 Hasan RA, Pak J, Kirk CJ, Friedland-Little JM, Chandler WL. Monitoring direct thrombin inhibitors with calibrated diluted thrombin time vs activated partial thromboplastin time in pediatric patients. Am J Clin Pathol 2023; 159 (01) 60-68
    CrossrefPubMedSearch in Google Scholar
  • 27 Tsu LV, Dager WE. Bivalirudin dosing adjustments for reduced renal function with or without hemodialysis in the management of heparin-induced thrombocytopenia. Ann Pharmacother 2011; 45 (10) 1185-1192
    CrossrefPubMedSearch in Google Scholar
  • 28 Hamzah M, Seelhammer TG, Yabrodi M. et al. Evaluation of bivalirudin dosing in pediatric extracorporeal membrane oxygenation with renal insufficiency or renal replacement therapy. ASAIO J 2022; 68 (11) e196-e203
    CrossrefPubMedSearch in Google Scholar
  • 29 Lahart MA, Burns EL, Streb MM. et al. Impact of continuous renal replacement therapy on bivalirudin dosing in pediatric extracorporeal membrane oxygenation. ASAIO J 2022; 68 (11) 1393-1398
    CrossrefPubMedSearch in Google Scholar
  • 30 Kiskaddon AL, Do NL, Williams P, Betensky M, Goldenberg NA. Anticoagulation with intravenous direct thrombin inhibitors in pediatric extracorporeal membrane oxygenation: A systematic review of the literature. Semin Thromb Hemost 2023; 49 (07) 756-763
    Thieme ConnectPubMedSearch in Google Scholar
  • 31 Lee CJ, Ansell JE. Direct thrombin inhibitors. Br J Clin Pharmacol 2011; 72 (04) 581-592
    CrossrefPubMedSearch in Google Scholar
  • 32 Young G, Boshkov LK, Sullivan JE. et al. Argatroban therapy in pediatric patients requiring nonheparin anticoagulation: an open-label, safety, efficacy, and pharmacokinetic study. Pediatr Blood Cancer 2011; 56 (07) 1103-1109
    CrossrefPubMedSearch in Google Scholar
  • 33 Beyer JT, Lind SE, Fisher S, Trujillo TC, Wempe MF, Kiser TH. Evaluation of intravenous direct thrombin inhibitor monitoring tests: Correlation with plasma concentrations and clinical outcomes in hospitalized patients. J Thromb Thrombolysis 2020; 49 (02) 259-267
    CrossrefPubMedSearch in Google Scholar
  • 34 Hirsh J, Anand SS, Halperin JL, Fuster V. Mechanism of action and pharmacology of unfractionated heparin. Arterioscler Thromb Vasc Biol 2001; 21 (07) 1094-1096
    CrossrefPubMedSearch in Google Scholar
  • 35 Massicotte P, Julian JA, Gent M. et al. REVIVE Study Group. An open-label randomized controlled trial of low molecular weight heparin compared to heparin and coumadin for the treatment of venous thromboembolic events in children: the REVIVE trial. Thromb Res 2003; 109 (2-3): 85-92
    CrossrefPubMedSearch in Google Scholar
  • 36 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
    CrossrefPubMedSearch in Google Scholar
  • 37 Sochet AA, Morrison JM, Jaffray J. et al. COVID-19 Anticoagulation in Children – Thromboprophylaxis (COVAC-TP) Trial Investigators. Enoxaparin Thromboprophylaxis in Children Hospitalized for COVID-19: A Phase 2 Trial. Pediatrics 2022; 150 (01) e2022056726
    CrossrefPubMedSearch in Google Scholar
  • 38 Faustino EVS, Raffini LJ, Hanson SJ. et al. for the CRETE Trial Investigators and the Pediatric Critical Care Blood Research Network (BloodNet) of the Pediatric Acute Lung Injury and Sepsis Investigators Network (PALISI), CRETE Trial Investigators: Clinical Coordinating Center, and, Data Coordinating Center, and, Outcomes Adjudication Committee, and, Data and Safety Monitoring Board, and, Independent Safety Monitor, and, Children's Hospital Wisconsin, and, Dell Children's Medical Center, and, Maria Fareri Children's Hospital, and, St. Louis Children's Hospital, and, University of Rochester Golisano Children's Hospital, and, Weill Cornell Medical Center, and, and Yale-New Haven Children's Hospital, and, for the CRETE Trial Investigators and the Pediatric Critical Care Blood Research Network (BloodNet) of the Pediatric Acute Lung Injury and Sepsis Investigators Network (PALISI) and CRETE Trial Investigators: Clinical Coordinating Center: and and and Data Coordinating Center: and and and Outcomes Adjudication Committee: and and and Data and Safety Monitoring Board: and and and Independent Safety Monitor: and and and Children's Hospital Wisconsin: and and and Dell Children's Medical Center: and and and Maria Fareri Children's Hospital: and and and St. Louis Children's Hospital: and and and University of Rochester Golisano Children's Hospital: and and and Weill Cornell Medical Center: and and and and Yale-New Haven Children's Hospital: and and. Age-dependent heterogeneity in the efficacy of prophylaxis with enoxaparin against catheter-associated thrombosis in critically ill children: A post hoc analysis of a Bayesian phase 2b randomized clinical trial. Crit Care Med 2021; 49 (04) e369-e380
    CrossrefPubMedSearch in Google Scholar
  • 39 O'Brien SH, Kulkarni R, Wallace A, Hamblin F, Burr S, Goldenberg NA. Multicenter dose-finding and efficacy and safety outcomes in neonates and children treated with dalteparin for acute venous thromboembolism. J Thromb Haemost 2014; 12 (11) 1822-1825
    CrossrefPubMedSearch in Google Scholar
  • 40 Moffett BS, Lee-Kim Y, Galati M. et al. Population pharmacokinetics of enoxaparin in pediatric patients. Ann Pharmacother 2018; 52 (02) 140-146
    CrossrefPubMedSearch in Google Scholar
  • 41 Pon TK, Dager WE, Roberts AJ, White RH. Subcutaneous enoxaparin for therapeutic anticoagulation in hemodialysis patients. Thromb Res 2014; 133 (06) 1023-1028
    CrossrefPubMedSearch in Google Scholar
  • 42 Bahabri A, Chan AKC, Belostosky V, Bhatt MD. Management of anticoagulation therapy in patients with thromboembolism in the context of renal dysfunction: challenging cases and practical algorithms. J Pediatr Hematol Oncol 2021; 43 (07) e1040-e1044
    CrossrefPubMedSearch in Google Scholar
  • 43 Koury J, Schnakenberg C, Villasenor C, Abraham S. A distinctive approach to venous thromboembolism treatment in a pediatric, hemodialysis patient: a case report. J Pediatr Pharmacol Ther 2021; 26 (01) 104-106
    PubMedSearch in Google Scholar
  • 44 Aszkiełowicz A, Steckiewicz KP, Okrągły M, Wujtewicz MA, Owczuk R. The impact of continuous veno-venous hemodiafiltration on the efficacy of administration of prophylactic doses of enoxaparin: a prospective observational study. Pharmaceuticals (Basel) 2023; 16 (08) 1166
    CrossrefPubMedSearch in Google Scholar
  • 45 Smythe MA, Priziola J, Dobesh PP, Wirth D, Cuker A, Wittkowsky AK. Guidance for the practical management of the heparin anticoagulants in the treatment of venous thromboembolism. J Thromb Thrombolysis 2016; 41 (01) 165-186
    CrossrefPubMedSearch in Google Scholar
  • 46 Warad D, Rao AN, Mullikin T. et al. A retrospective analysis of outcomes of dalteparin use in pediatric patients: a single institution experience. Thromb Res 2015; 136 (02) 229-233
    CrossrefPubMedSearch in Google Scholar
  • 47 Lutkin M, Stronach L, Yadav P, Hothi DK. Dalteparin anticoagulation in paediatric home haemodialysis. Pediatr Nephrol 2018; 33 (12) 2337-2341
    CrossrefPubMedSearch in Google Scholar
  • 48 Musgrave KM, Webber K, Murphy P, Avery P, Biss TT. Evaluation of the age-dependent dosing recommendations for the administration of daily tinzaparin in children with thrombosis. J Thromb Haemost 2017; 15 (12) 2361-2366
    CrossrefPubMedSearch in Google Scholar
  • 49 Roeleveld PP, van der Hoeven A, de Wilde RB, Eikenboom J, Smiers FJ, Bunker-Wiersma HE. Higher tinzaparin dosing is needed to achieve target anti-xa levels in pediatric cardiac intensive care patients. Pediatr Crit Care Med 2016; 17 (03) 203-209
    CrossrefPubMedSearch in Google Scholar
  • 50 Kuhle S, Massicotte P, Dinyari M. et al. Dose-finding and pharmacokinetics of therapeutic doses of tinzaparin in pediatric patients with thromboembolic events. Thromb Haemost 2005; 94 (06) 1164-1171
    Thieme ConnectPubMedSearch in Google Scholar
  • 51 Helfer H, Siguret V, Mahé I. Tinzaparin sodium pharmacokinetics in patients with chronic kidney disease: practical implications. Am J Cardiovasc Drugs 2020; 20 (03) 223-228
    CrossrefPubMedSearch in Google Scholar
  • 52 Mahé I, Aghassarian M, Drouet L. et al. Tinzaparin and enoxaparin given at prophylactic dose for eight days in medical elderly patients with impaired renal function: a comparative pharmacokinetic study. Thromb Haemost 2007; 97 (04) 581-586
    Thieme ConnectPubMedSearch in Google Scholar
  • 53 Projean D, Lalonde S, Morin J. et al. Study of the bioaccumulation of tinzaparin in renally impaired patients when given at prophylactic doses - The STRIP study. Thromb Res 2019; 174: 48-50
    CrossrefPubMedSearch in Google Scholar
  • 54 Yeung J, Dix CHK, Ritchie AG, Kow M, Chen VMY. Tinzaparin for venous thromboembolism in patients with renal impairment: a single-centre, prospective pilot study. Intern Med J 2023; 53 (01) 68-73
    CrossrefPubMedSearch in Google Scholar
  • 55 Nadar SK, Goyal D, Shantsila E, Banerjee P, Lip GY. Fondaparinux: an overview. Expert Rev Cardiovasc Ther 2009; 7 (06) 577-585
    CrossrefPubMedSearch in Google Scholar
  • 56 Ko RH, Michieli C, Lira JL, Young G. FondaKIDS II: long-term follow-up data of children receiving fondaparinux for treatment of venous thromboembolic events. Thromb Res 2014; 134 (03) 643-647
    CrossrefPubMedSearch in Google Scholar
  • 57 Al-Shaer MH, Ibrahim T. Safety and efficacy of fondaparinux in renal impairment. J Pharm Technol 2015; 31 (04) 161-166
    CrossrefPubMedSearch in Google Scholar
  • 58 Mismetti P, Samama CM, Rosencher N. et al. PROPICE Study Group. Venous thromboembolism prevention with fondaparinux 1.5 mg in renally impaired patients undergoing major orthopaedic surgery. A real-world, prospective, multicentre, cohort study. Thromb Haemost 2012; 107 (06) 1151-1160
    Thieme ConnectPubMedSearch in Google Scholar
  • 59 Turpie AG, Lensing AW, Fuji T, Boyle DA. Pharmacokinetic and clinical data supporting the use of fondaparinux 1.5 mg once daily in the prevention of venous thromboembolism in renally impaired patients. Blood Coagul Fibrinolysis 2009; 20 (02) 114-121
    CrossrefPubMedSearch in Google Scholar
  • 60 Zufferey PJ, Ollier E, Delavenne X, Laporte S, Mismetti P, Duffull SB. Incidence and risk factors of major bleeding following major orthopaedic surgery with fondaparinux thromboprophylaxis. A time-to-event analysis. Br J Clin Pharmacol 2018; 84 (10) 2242-2251
    CrossrefPubMedSearch in Google Scholar
  • 61 Kalicki RM, Aregger F, Alberio L, Lämmle B, Frey FJ, Uehlinger DE. Use of the pentasaccharide fondaparinux as an anticoagulant during haemodialysis. Thromb Haemost 2007; 98 (06) 1200-1207
    Thieme ConnectPubMedSearch in Google Scholar
  • 62 Sombolos KI, Fragia TK, Gionanlis LC. et al. Use of fondaparinux as an anticoagulant during hemodialysis: a preliminary study. Int J Clin Pharmacol Ther 2008; 46 (04) 198-203
    CrossrefPubMedSearch in Google Scholar
  • 63 Speeckaert MM, Devreese KM, Vanholder RC, Dhondt A. Fondaparinux as an alternative to vitamin K antagonists in haemodialysis patients. Nephrol Dial Transplant 2013; 28 (12) 3090-3095
    CrossrefPubMedSearch in Google Scholar
  • 64 Cope J, Bushwitz J, An G, Antigua A, Patel A, Zumberg M. Clinical experience with prophylactic fondaparinux in critically ill patients with moderate to severe renal impairment or renal failure requiring renal replacement therapy. Ann Pharmacother 2015; 49 (03) 270-277
    CrossrefPubMedSearch in Google Scholar
  • 65 Michaličková D, Hartinger JM, Hladinová Z. et al. Population pharmacokinetics-pharmacodynamics of fondaparinux in dialysis-dependent chronic kidney disease patients undergoing chronic renal replacement therapy. Eur J Clin Pharmacol 2022; 78 (01) 99
    CrossrefPubMedSearch in Google Scholar
  • 66 Johnson PN, Benefield EC, Bui PY, Marlar RA, Gessouroun MR. Fondaparinux in an obese child with heparin-induced thrombocytopenia and a history of renal failure. J Pediatr Pharmacol Ther 2013; 18 (04) 303-310
    PubMedSearch in Google Scholar
  • 67 Sharathkumar AA, Crandall C, Lin JJ, Pipe S. Treatment of thrombosis with fondaparinux (Arixtra) in a patient with end-stage renal disease receiving hemodialysis therapy. J Pediatr Hematol Oncol 2007; 29 (08) 581-584
    CrossrefPubMedSearch in Google Scholar
  • 68 Johnson PN, Benefield EC, Bui PY, Gausman JN, Marlar RA, Gessouroun MR. Fondaparinux monitoring: Need for a local fondaparinux-calibrated anti-factor Xa assay. J Pediatr Pharmacol Ther 2013; 18 (04) 318-319
    PubMedSearch in Google Scholar
  • 69 Bijsterveld NR, Moons AH, Boekholdt SM. et al. Ability of recombinant factor VIIa to reverse the anticoagulant effect of the pentasaccharide fondaparinux in healthy volunteers. Circulation 2002; 106 (20) 2550-2554
    CrossrefPubMedSearch in Google Scholar
  • 70 Orso D, Fonda F, Brussa A. et al. Andexanet alpha versus four-factor prothrombin complex concentrate in DOACs anticoagulation reversal: an updated systematic review and meta-analysis. Crit Care 2024; 28 (01) 221
    CrossrefPubMedSearch in Google Scholar
  • 71 Rodriguez V, Stanek J, Kerlin BA, Dunn AL. Andexanet alfa versus prothrombin complex concentrates/blood products as apixaban/rivaroxaban reversal agents: A survey among pediatric hematologists. Clin Appl Thromb Hemost 2022;28:10760296221078842
    PubMed
  • 72 Samama MM. The mechanism of action of rivaroxaban–an oral, direct Factor Xa inhibitor–compared with other anticoagulants. Thromb Res 2011; 127 (06) 497-504
    CrossrefPubMedSearch in Google Scholar
  • 73 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
    CrossrefPubMedSearch in Google Scholar
  • 74 McCrindle BW, Michelson AD, Van Bergen AH. et al. UNIVERSE Study Investigators *. Thromboprophylaxis for Children Post-Fontan Procedure: Insights From the UNIVERSE Study. [published correction appears in J Am Heart Assoc 2021;10(24):e020766. doi: 10.1161/JAHA.120.020766] J Am Heart Assoc 2021; 10 (22) e021765
    CrossrefPubMedSearch in Google Scholar
  • 75 Volkl AA, Moore KT, Haskell L, Barnathan ES. Updated Renal Dosage Recommendations for rivaroxaban in patients experiencing or at risk of thromboembolic disease. Am J Cardiovasc Drugs 2023; 23 (03) 247-255
    CrossrefPubMedSearch in Google Scholar
  • 76 Elenjickal EJ, Travlos CK, Marques P, Mavrakanas TA. Anticoagulation in patients with chronic kidney disease. Am J Nephrol 2024; 55 (02) 146-164
    CrossrefPubMedSearch in Google Scholar
  • 77 Kao TW, Chen ZW, Lin YH. Anticoagulation for patients with concomitant atrial fibrillation and end-stage renal disease: A systematic review and network meta-analysis. J Am Heart Assoc 2024; 13 (08) e034176
    CrossrefPubMedSearch in Google Scholar
  • 78 Adcock DM, Gosselin R. Direct oral anticoagulants (DOACs) in the laboratory: 2015 Review. Thromb Res 2015; 136 (01) 7-12
    CrossrefPubMedSearch in Google Scholar
  • 79 Jiménez D, Yusen RD, Ramacciotti E. Apixaban: an oral direct factor-xa inhibitor. Adv Ther 2012; 29 (03) 187-201
    CrossrefPubMedSearch in Google Scholar
  • 80 ClinicalTrials.gov. Apixaban for the acute treatment of venous thromboembolism in children. 2023 . ClinicalTrials.gov identifier: NCT02464969. Last Updated October 29, 2024. Accessed December 26, 2024 at: https://clinicaltrials.gov/study/NCT02464969
    PubMedSearch in Google Scholar
  • 81 O'Brien SH, Rodriguez V, Lew G. et al. PREVAPIX-ALL investigators. Apixaban versus no anticoagulation for the prevention of venous thromboembolism in children with newly diagnosed acute lymphoblastic leukaemia or lymphoma (PREVAPIX-ALL): a phase 3, open-label, randomised, controlled trial. [published correction appears in Lancet Haematol 2024;11(6):e399. doi: 10.1016/S2352-3026(24)00113-3] Lancet Haematol 2024; 11 (01) e27-e37
    CrossrefPubMedSearch in Google Scholar
  • 82 Payne RM, Burns KM, Glatz AC. et al. Apixaban for prevention of thromboembolism in pediatric heart disease. J Am Coll Cardiol 2023; 82 (24) 2296-2309
    CrossrefPubMedSearch in Google Scholar
  • 83 Poulakos M, Walker JN, Baig U, David T. Edoxaban: A direct oral anticoagulant. Am J Health Syst Pharm 2017; 74 (03) 117-129
    CrossrefPubMedSearch in Google Scholar
  • 84 van Ommen CH, Albisetti M, Chan AK. et al. The Edoxaban Hokusai VTE PEDIATRICS Study: An open-label, multicenter, randomized study of edoxaban for pediatric venous thromboembolic disease. Res Pract Thromb Haemost 2020; 4 (05) 886-892 P
    CrossrefPubMedSearch in Google Scholar
  • 85 Portman MA, Jacobs JP, Newburger JW. et al. ENNOBLE-ATE Trial Investigators. Edoxaban for thromboembolism prevention in pediatric patients with cardiac disease. J Am Coll Cardiol 2022; 80 (24) 2301-2310
    CrossrefPubMedSearch in Google Scholar
  • 86 Bathala MS, Masumoto H, Oguma T, He L, Lowrie C, Mendell J. Pharmacokinetics, biotransformation, and mass balance of edoxaban, a selective, direct factor Xa inhibitor, in humans. Drug Metab Dispos 2012; 40 (12) 2250-2255
    CrossrefPubMedSearch in Google Scholar
  • 87 Wienen W, Stassen JM, Priepke H, Ries UJ, Hauel N. In-vitro profile and ex-vivo anticoagulant activity of the direct thrombin inhibitor dabigatran and its orally active prodrug, dabigatran etexilate. Thromb Haemost 2007; 98 (01) 155-162
    PubMedSearch in Google Scholar
  • 88 Halton J, Brandão LR, Luciani M. et al. DIVERSITY Trial Investigators. Dabigatran etexilate for the treatment of acute venous thromboembolism in children (DIVERSITY): a randomised, controlled, open-label, phase 2b/3, non-inferiority trial. Lancet Haematol 2021; 8 (01) e22-e33
    CrossrefPubMedSearch in Google Scholar
  • 89 Parasrampuria DA, Marbury T, Matsushima N. et al. Pharmacokinetics, safety, and tolerability of edoxaban in end-stage renal disease subjects undergoing haemodialysis. Thromb Haemost 2015; 113 (04) 719-727
    Thieme ConnectPubMedSearch in Google Scholar
  • 90 Stafford DW. The vitamin K cycle. J Thromb Haemost 2005; 3 (08) 1873-1878
    CrossrefPubMedSearch in Google Scholar
  • 91 Streif W, Andrew M, Marzinotto V. et al. Analysis of warfarin therapy in pediatric patients: A prospective cohort study of 319 patients. Blood 1999; 94 (09) 3007-3014
    CrossrefPubMedSearch in Google Scholar
  • 92 Bonduel M, Sciuccati G, Hepner M. et al. Acenocoumarol therapy in pediatric patients. J Thromb Haemost 2003; 1 (08) 1740-1743
    CrossrefPubMedSearch in Google Scholar
  • 93 Andrew M, Marzinotto V, Brooker LA. et al. Oral anticoagulation therapy in pediatric patients: a prospective study. Thromb Haemost 1994; 71 (03) 265-269
    Thieme ConnectPubMedSearch in Google Scholar
  • 94 Bonduel MM. Oral anticoagulation therapy in children. Thromb Res 2006; 118 (01) 85-94
    CrossrefPubMedSearch in Google Scholar
  • 95 Hirsh J, Fuster V, Ansell J, Halperin JL. American Heart Association/American College of Cardiology Foundation. American Heart Association/American College of Cardiology Foundation guide to warfarin therapy. J Am Coll Cardiol 2003; 41 (09) 1633-1652
    PubMedSearch in Google Scholar
  • 96 Limdi NA, Limdi MA, Cavallari L. et al. Warfarin dosing in patients with impaired kidney function. Am J Kidney Dis 2010; 56 (05) 823-831
    CrossrefPubMedSearch in Google Scholar