Prevention of thrombotic complications in critically ill children

Tsygankov A.E.; Aleksandrovich Yu.S.; Lekmanov A.U.; Afukov I.I.; Gorokhov D.V.; Kostomarova E.A.

doi:https://doi.org/10.17116/anaesthesiology202302184

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BACKGROUND

Thrombotic complications are common in critically ill children requiring prolonged intensive care. Identification of risk factors of thrombosis with simultaneous assessment of the likelihood of hemorrhagic complications underlies decision making on prevention of hypercoagulation. However, there are currently no clear recommendations and schemes of anticoagulation for certain diseases.

OBJECTIVE

To analyze risk factors, current methods of prevention and treatment of thrombotic complications in critically ill children.

MATERIAL AND METHODS

We analyzed 65 articles in the PubMed and Russian Science Citation Index databases between 2017 and 2022. The following keywords were used: «thromboprophylaxis», «thromboembolism», «intensive care unit», «critical care», «pediatric», «thrombosis in children», «thromboprophylaxis in children».

RESULTS

The main risk factors of thrombotic complications in children are age up to one year and severe diseases requiring long-term immobilization and accompanied by coagulopathy.

CONCLUSION

The main method of preventing thrombotic complications in children is the earliest possible motor activity of ICU patients. The most effective drugs are high and low molecular weight heparins, although there is currently no clear opinion.

Keywords:

thrombosis

thrombotic complications

thromboprophylaxis

intensive care

children

Authors:

Tsygankov A.E.

Morozovskaya Children’s City Clinical Hospital;
Research Institute for Healthcare Organization and Medical Management

ORCID: 0000-0003-3600-2801

Aleksandrovich Yu.S.

Children’s Scientific Clinical Center for Infectious Diseases

ORCID: 0000-0002-2131-4813

Lekmanov A.U.

Pirogov Russian National Research Medical University

ORCID: 0000-0003-0798-1625

Afukov I.I.

Pirogov Russian National Research Medical University;
Moscow Healthcare Department

ORCID: 0000-0001-9850-6779

Gorokhov D.V.

Morozovskaya Children’s City Clinical Hospital

ORCID: 0000-0003-0517-3376

Kostomarova E.A.

Filatov Children’s City Clinical Hospital

ORCID: 0000-0003-0635-0397

Received:

28.07.2022

Accepted:

14.12.2022

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References:

Biss TT, Brandão LR, Kahr WH, Chan AK, Williams S. Clinical features and outcome of pulmonary embolism in children. British Journal of Haematology. 2008;142(5):808-818. https://doi.org/10.1111/j.1365-2141.2008.07243.x
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(4):1001-1008. https://doi.org/10.1542/peds.2009-0768
Boulet SL, Grosse SD, Thornburg CD, Yusuf H, Tsai J, Hooper WC. Trends in venous thromboembolism-related hospitalizations, 1994-2009. Pediatrics. 2012;130:812-820. https://doi.org/10.1542/peds.2012-0267
Engel ER, Nguyen ATH, Amankwah EK, Albisetti M, Brandão LR, Goldenberg NA, Betensky M. Predictors of postthrombotic syndrome in pediatric thrombosis: A systematic review and meta-analysis of the literature. Journal of Thrombosis and Haemostasis. 2020;18(10):2601-2612. https://doi.org/10.1111/jth.14984
Branchford BR, Betensky M, Goldenberg NA. Pediatric issues in thrombosis and hemostasis: The how and why of venous thromboembolism risk stratification in hospitalized children. Thrombosis Research. 2018;172:190-193. https://doi.org/10.1016/j.thromres.2018.02.010
Goldenberg NA. Long-term outcomes of venous thrombosis in children. Current Opinion in Hematology. 2005;12(5):370-376. https://doi.org/10.1097/01.moh.0000160754.55131.14
Ishola T, Kirk SE, Guffey D, Voigt K, Shah MD, Srivaths L. Risk factors and co-morbidities in adolescent thromboembolism are different than those in younger children. Thrombosis Research. 2016;141:178-182. https://doi.org/10.1016/j.thromres.2016.03.021
Park ES, Choi HS, Lee KS, Kim SW, Lee JM. Venous thromboembolism in children and young adults in Korea: analysis of the Korean health insurance review and assessment service database. Journal of Korean Medical Science. 2019;34(49):e316. https://doi.org/10.3346/jkms.2019.34.e316
Hanson SJ, Faustino EV, Mahajerin A, O’Brien SH, Streck CJ, Thompson AJ, Petrillo TM, Petty JK. Recommendations for venous thromboembolism prophylaxis in pediatric trauma patients: A national, multidisciplinary consensus study. The Journal of Trauma and Acute Care Surgery. 2016;80(5):695-701. https://doi.org/10.1097/TA.0000000000000962
Higgerson RA, Lawson KA, Christie LM, Brown AM, McArthur JA, Totapally BR, Hanson SJ; National Association of Childrenʼs Hospitals and Related Institutionʼs Pediatric Intensive Care Unit FOCUS group. Incidence and risk factors associated with venous thrombotic events in pediatric intensive care unit patients. Pediatric Critical Care Medicine. 2011;12(6):628-634. https://doi.org/10.1097/PCC.0b013e318207124a
Takemoto CM, Sohi S, Desai K, Bharaj R, Khanna A, McFarland S, Klaus S, Irshad A, Goldenberg NA, Strouse JJ, Streiff MB. Hospital-associated venous thromboembolism in children: incidence and clinical characteristics. The Journal of Pediatrics. 2014;164(2):332-338. https://doi.org/10.1016/j.jpeds.2013.10.025
Citla Sridhar D, Abou-Ismail MY, Ahuja SP. Central venous catheter-related thrombosis in children and adults. Thrombosis Research. 2020;187:103-112. https://doi.org/10.1016/j.thromres.2020.01.017
Monagle P, Chan AKC, Goldenberg NA, Ichord RN, Journeycake JM, Nowak-Göttl U, Vesely SK. 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):737-801. https://doi.org/10.1378/chest.11-2308
Berezhanskiy BV, Zhevnerev AA. Catheter-associated bloodstream infections. Klinicheskaya mikrobiologiya, antimikrobnaya khimioterapiya. 2006;8(2): 130-142. (In Russ.).
Chubarova AI, Kostomarova EA, Zhikhareva NS, Radchenko ER. Reducing the frequency of complications when using tunneled catheters in children with short bowel syndrome who are on home parenteral nutrition. Rossijskij vestnik detskoj khirurgii, anesteziologii i reanimatologii. 2015;5:98-106. (In Russ.). https://doi.org/10.17816/psaic137
Revel-Vilk S. Central venous line-related thrombosis in children. Acta Haematologica. 2006;115(3-4):201-206. https://doi.org/10.1159/000090936
Gandullia P, Lugani F, Costabello L, Arrigo S, Calvi A, Castellano E, Vignola S, Pistorio A, Barabino AV. Long-term home parenteral nutrition in children with chronic intestinal failure: A 15-year experience at a single Italian centre. Digestive and Liver Disease. 2011;43(1):28-33. https://doi.org/10.1016/j.dld.2010.04.012
Cordero Cruz AM, Aguilella Vizcaíno MJ, González Fuentes C, Rubio Murillo M, Moreno Villares JM, Gomis Muñoz P, Herreros de Tejada A. [Home parenteral nutrition in infants and children in a tertiary level hospital between 1993 and 2009]. Nutricion Hospitalaria. 2012;27(1):262-265. (In Spanish). https://doi.org/10.1590/S0212-16112012000100034
Malec LM, Cooper J, Rudolph J, Michaels MG, Ragni MV. Prophylactic rtPA in the prevention of line-associated thrombosis and infection in short bowel syndrome. Journal of Pediatric Gastroenterology and Nutrition. 2018;66(6):972-975. https://doi.org/10.1097/MPG.0000000000001836
Baskin JL, Pui CH, Reiss U, Wilimas JA, Metzger ML, Ribeiro RC, Howard SC. Management of occlusion and thrombosis associated with long-term indwelling central venous catheters. Lancet. 2009;374(9684):159-169. https://doi.org/10.1016/S0140-6736(09)60220-8
Saxonhouse MA, Burchfield DJ. The evaluation and management of postnatal thromboses. Journal of Perinatology. 2009;29(7):467-478. https://doi.org/10.1038/jp.2009.14
Zharkov PA, Morozova DS, Gobadze DA, Evstratov DA, Fedorova DV, Zharikova LI, Pshonkin AV, Novichkova GA. Deep veins thrombosis in children with blood diseases. Onkogematologiya. 2019;14(1):20-30. (In Russ.). https://doi.org/10.17650/1818-8346-2019-14-1-20-30
Tsygankov AE, Afukov II, Vlasova AV, Glazyrina AA, Larina LE, Gitinovasov RS, Kurbanova SKh, Chudina OS. Life-threatening thrombotic complications in a pediatric in the intensive care unit. Detskaya khirurgiya. Zhurnal im. Yu.F. Isakova. 2021;25(6):386-391. (In Russ.). https://doi.org/10.55308/1560-9510-2021-25-6-386-391
Arlikar SJ, Atchison CM, Amankwah EK, Ayala IA, Barrett LA, Branchford BR, Streiff MB, Takemoto CM, Goldenberg NA. Development of a new risk score for hospital-associated venous thromboembolism in critically-ill children not undergoing cardiothoracic surgery. Thrombosis Research. 2015;136(4):717-722. https://doi.org/10.1016/j.thromres.2015.04.036
Horton DB, Xie F, Chen L, Mannion ML, Curtis JR, Strom BL, Beukelman T. Oral glucocorticoids and incident treatment of diabetes mellitus, hypertension, and venous thromboembolism in children. American Journal of Epidemiology. 2021;190(3):403-412. https://doi.org/10.1093/aje/kwaa197
Johannesdottir SA, Horváth-Puhó E, Dekkers OM, Cannegieter SC, Jørgensen JO, Ehrenstein V, Vandenbroucke JP, Pedersen L, Sørensen HT. Use of glucocorticoids and risk of venous thromboembolism: a nationwide population-based case-control study. JAMA Internal Medicine. 2013;173(9):743-752. https://doi.org/10.1001/jamainternmed.2013.122
Morgan J, Checketts M, Arana A, Chalmers E, Maclean J, Powis M, Morton N; Association of paediatric anaesthetists of Great Britain and Ireland Guidelines Working Group on Thromboprophylaxis in Children. Prevention of perioperative venous thromboembolism in pediatric patients: Guidelines from the Association of Paediatric Anaesthetists of Great Britain and Ireland (APAGBI). Pediatric Anesthesia. 2018;28(5):382-391. https://doi.org/10.1111/pan.13355
Noone DG, Iijima K, Parekh R. Idiopathic nephrotic syndrome in children. Lancet. 2018;392(10141):61-74. https://doi.org/10.1016/S0140-6736(18)30536-1
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. Journal of Pediatric Hematology/Oncology. 2020;37(2):109-118. https://doi.org/10.1080/08880018.2019.1695030
Lau BC, Jagodzinski J, Pandya NK. Incidence of symptomatic pulmonary embolus and deep vein thrombosis after knee arthroscopy in the pediatric and adolescent population. Clinical Journal of Sport Medicine. 2019; 29(4):276-280. https://doi.org/10.1097/JSM.0000000000000519
Murphy RF, Naqvi M, Miller PE, Feldman L, Shore BJ. Pediatric orthopaedic lower extremity trauma and venous thromboembolism. Journal of Children’s Orthopaedics. 2015;9(5):381-384. https://doi.org/10.1007/s11832-015-0697-1
Pannucci CJ, Osborne NH, Wahl WL. Venous thromboembolism in thermally injured patients: analysis of the National Burn Repository. Journal of Burn Care and Research. 2011;32(1):6-12. https://doi.org/10.1097/BCR.0b013e318204b2ff
Arina P, Singer M. Pathophysiology of sepsis. Current Opinion in Anaesthesiology. 20211;34(2):77-84. https://doi.org/10.1097/ACO.0000000000000963
Ito T, Kakuuchi M, Maruyama I. Endotheliopathy in septic conditions: mechanistic insight into intravascular coagulation. Critical Care. 2021;25(1):95. https://doi.org/10.1186/s13054-021-03524-6
Wu R, Wang N, Comish PB, Tang D, Kang R. Inflammasome-dependent coagulation activation in sepsis. Frontiers in Immunology. 2021;12:641750. https://doi.org/10.3389/fimmu.2021.641750
Smith L. Disseminated intravascular coagulation. Seminars in Oncology Nursing. 2021;37(2):151135. https://doi.org/10.1016/j.soncn.2021.151135
Bhakta S, Erben Y, Sanghavi D, Fortich S, Li Y, Hasan MM, Dong Y, Brigham TJ, Edwards MA, Meschia JF, Franco PM. A systematic review and meta-analysis of racial disparities in deep vein thrombosis and pulmonary embolism events in patients hospitalized with coronavirus disease 2019. Journal of Vascular Surgery: Venous and Lymphatic Disorders. 2022;10(4):939-944.e3. https://doi.org/10.1016/j.jvsv.2022.03.003
Aardoom MA, Klomberg RCW, Kemos P, Ruemmele FM; PIBD-VTE Group; van Ommen CHH, de Ridder L, Croft NM; PIBD-SETQuality Consortium. The incidence and characteristics of venous thromboembolisms in paediatric-onset inflammatory bowel disease: A prospective international cohort study based on the PIBD-SETQuality Safety Registry. The Journal of Crohn’s and Colitis. 2022;16(5):695-707. https://doi.org/10.1093/ecco-jcc/jjab171
Jaffray J, Branchford B, Goldenberg N, Malvar J, Croteau SE, Silvey M, Fargo JH, Cooper JD, Bakeer N, Sposto R, Ji L, Zakai NA, Faustino EVS, Stillings A, Krava E, Young G, Mahajerin A. Development of a risk model for pediatric hospital-acquired thrombosis: A report from the children’s hospital-acquired thrombosis consortium. The Journal of Pediatrics. 2021;228: 252-259.e1. https://doi.org/10.1016/j.jpeds.2020.09.016
Jaffray J, Branchford B, Goldenberg N, Malvar J, Croteau SE, Silvey M, Fargo JH, Cooper JD, Bakeer N, Sposto R, Ji L, Zakai NA, Faustino EVS, Stillings A, Krava E, Young G, Mahajerin A. Alteplase for the treatment of central venous catheter occlusion in children: results of a prospective, open-label, single-arm study (The Cathflo Activase Pediatric Study). Journal of Vascular and Interventional Radiology. 2006;17(11 Pt 1):1745-1751. https://doi.org/10.1097/01.RVI.0000241542.71063.83
Tian L, Li W, Su Y, Gao H, Yang Q, Lin P, Wang L, Zeng J, Li Y. Risk factors for central venous access device-related thrombosis in hospitalized children: A systematic review and meta-analysis. Thrombosis and Haemostasis. 2021;121(5):625-640. https://doi.org/10.1055/s-0040-1720976
Dillon PW, Jones GR, Bagnall-Reeb HA, Buckley JD, Wiener ES, Haase GM; Children’s Oncology Group. Prophylactic urokinase in the management of long-term venous access devices in children: A Children’s Oncology Group study. Journal of Clinical Oncology. 2004;22(13):2718-2723. https://doi.org/10.1200/JCO.2004.07.019
Faraoni D, Emani S, Halpin E, Bernier R, Emani SM, DiNardo JA, Ibla JC. Relationship between transfusion of blood products and the incidence of thrombotic complications in neonates and infants undergoing cardiac surgery. Journal of Cardiothoracic and Vascular Anesthesia. 2017;31(6): 1943-1948. https://doi.org/10.1053/j.jvca.2017.04.039
Ho KM, Tan JA. Stratified meta-analysis of intermittent pneumatic compression of the lower limbs to prevent venous thromboembolism in hospitalized patients. Circulation. 2013;128(9):1003-1020. https://doi.org/10.1161/CIRCULATIONAHA.113.002690
Bujold KE, Halstead ES, Xavier F. Continuous low-dose heparin infusion for catheter-related thrombosis prophylaxis in critically-ill children. Blood. 2020;136(suppl 1):9-10. https://doi.org/10.1182/blood-2020-133914
Omatsu D, Thompson K, Maglasang B, Yuasa H, Kimata C. Heparin versus normal saline: flushing effectiveness in managing central venous catheters in pediatric patients with cancer. Clinical Journal of Oncology Nursing. 2022;26(3):300-307. https://doi.org/10.1188/22.CJON.300-307
Avila ML, Shah PS, Brandão LR. Different unfractionated heparin doses for preventing arterial thrombosis in children undergoing cardiac catheterization. The Cochrane Database of Systematic Reviews. 2020;2(2):CD010196. https://doi.org/10.1002/14651858.CD010196.pub3
Faustino EVS. Central venous catheter-associated deep venous thrombosis in critically ill children. Seminars of Thrombosis and Haemostasis. 2018;44(1):52-56. https://doi.org/10.1055/s-0037-1603938
Pelland-Marcotte MC, Amiri N, Avila ML, Brandão LR. Low molecular weight heparin for prevention of central venous catheter-related thrombosis in children. The Cochrane Database of Systematic Reviews. 2020;6(6):CD005982. https://doi.org/10.1002/14651858.CD005982.pub3
Faustino EVS, Shabanova V, Raffini LJ, Kandil SB, Li S, Pinto MG, Cholette JM, Hanson SJ, Nellis ME, Silva CT, Chima R, Sharathkumar A, Thomas KA, McPartland T, Tala JA, Spinella PC; CRETE Trial Investigators and the Pediatric Critical Care Blood Research Network (BloodNet) of the Pediatric Acute Lung Injury and Sepsis Investigators Network (PALISI). Efficacy of early prophylaxis against catheter-associated thrombosis in critically ill children: A bayesian phase 2b randomized clinical trial. Critical Care Medicine. 2021;49(3):235-246. https://doi.org/10.1097/CCM.0000000000004784
Faustino EVS, Raffini LJ, Hanson SJ, Cholette JM, Pinto MG, Li S, Kandil SB, Nellis ME, Shabanova V, Silva CT, Tala JA, McPartland T, Spinella PC; 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. 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. Critical Care Medicine. 2021;49(4):369-380. https://doi.org/10.1097/CCM.0000000000004848
Clark HH, Ballester L, Whitworth H, Raffini L, Witmer C. Prevention of recurrent thrombotic events in children with central venous catheter-associated venous thrombosis. Blood. 2022;139(3):452-460. https://doi.org/10.1182/blood.2021013453
Mahajerin A, Petty JK, Hanson SJ, Thompson AJ, O’Brien SH, Streck CJ, Petrillo TM, Faustino EV. 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. Journal of Trauma and Acute Care Surgery. 2017;82(3):627-636. https://doi.org/10.1097/TA.0000000000001359
Byrne JP, Geerts W, Mason SA, Gomez D, Hoeft C, Murphy R, Neal M, Nathens AB. Effectiveness of low-molecular-weight heparin versus unfractionated heparin to prevent pulmonary embolism following major trauma: A propensity-matched analysis. Journal of Trauma and Acute Care Surgery. 2017;82(2):252-262. https://doi.org/10.1097/TA.0000000000001321
Culbert MH, Hamidi M, Zeeshan M, Hanna K, Romero A, Joseph B, O’Keeffe T. Retrospective analysis of low-molecular-weight heparin and unfractionated heparin in pediatric trauma patients: a comparative analysis. Journal of Surgical Research. 2020;249:121-129. https://doi.org/10.1016/j.jss.2019.11.019
Khurrum M, Asmar S, Henry M, Ditillo M, Chehab M, Tang A, Bible L, Gries L, Joseph B. The survival benefit of low molecular weight heparin over unfractionated heparin in pediatric trauma patients. Journal of Pediatric Surgery. 2021;56(3):494-499. https://doi.org/10.1016/j.jpedsurg.2020.07.021
Gatt D, Ben-Shimol S, Hazan G, Golan Tripto I, Goldbart A, Aviram M. Comparison of septic and nonseptic pulmonary embolism in children. Pediatric Pulmonology. 2021;56(10):3395-3401. https://doi.org/10.1002/ppul.25604
Ye R, Zhao L, Wang C, Wu X, Yan H. Clinical characteristics of septic pulmonary embolism in adults: A systematic review. Respiratory Medicine. 2014;108(1):1-8. https://doi.org/10.1016/j.rmed.2013.10.012
Story E, Bijelic V, Penney C, Benchimol EI, Halton J, Mack DR. Safety of venous thromboprophylaxis with low-molecular-weight heparin in children with ulcerative colitis. Journal of Pediatric Gastroenterology and Nutrition. 2021;73(5):604-609. https://doi.org/10.1097/MPG.0000000000003231
Sharathkumar AA, Faustino EVS, Takemoto CM. How we approach thrombosis risk in children with COVID-19 infection and MIS-C. Journal of Parenteral and Enteral Nutrition. 2021;68(7):e29049. https://doi.org/10.1002/pbc.29049
Vegting IL, Tabbers MM, Benninga MA, Wilde JC, Serlie MJ, Tas TA, Jonkers CF, van Ommen CH. Prophylactic anticoagulation decreases catheter-related thrombosis and occlusion in children with home parenteral nutrition. JPEN: Journal of Parenteral and Enteral Nutrition. 2012;36(4):456-462. https://doi.org/10.1177/0148607111416482
Schmidt ML, Wendel D, Horslen SP, Lane ER, Brandão LR, Gottschalk E, Belza C, Courtney-Martin G, Wales PW, Avitzur Y. Secondary anticoagulation prophylaxis for catheter-related thrombosis in pediatric intestinal failure: comparison of short- vs long-term treatment protocols. JPEN: Journal of Parenteral and Enteral Nutrition. 2021;45(7):1432-1440. https://doi.org/10.1002/jpen.2055
Ragni MV, Journeycake JM, Brambilla DJ. Tissue plasminogen activator to prevent central venous access device infections: a systematic review of central venous access catheter thrombosis, infection and thromboprophylaxis. Haemophilia. 2008;14(1):30-38. https://doi.org/10.1111/j.1365-2516.2007.01599.x
Barzaghi A, Dell’Orto M, Rovelli A, Rizzari C, Colombini A, Uderzo C. Central venous catheter clots: incidence, clinical significance and catheter care in patients with hematologic malignancies. Pediatric Hematology and Oncology. 1995;12(3):243-250. https://doi.org/10.3109/08880019509029565
Leiden mutation. Accessed October 24, 2022. https://www.medzhencentre.ru/article/mutaciya-leydena
Modi BP, Langer M, Ching YA, Valim C, Waterford SD, Iglesias J, Duro D, Lo C, Jaksic T, Duggan C. Improved survival in a multidisciplinary short bowel syndrome program. Journal of Pediatric Surgery. 2008;43(1):20-24. https://doi.org/10.1016/j.jpedsurg.2007.09.014
Monagle P, Newall F. Management of thrombosis in children and neonates: practical use of anticoagulants in children. Hematology: the American Society of Hematology Education Program. 2018;(1):399-404. https://doi.org/10.1182/asheducation-2018.1.399
Chow SL, Zammit K, West K, Dannenhoffer M, Lopez-Candales A. Correlation of antifactor Xa concentrations with renal function in patients on enoxaparin. Journal of Clinical Pharmacology. 2003;43(6):586-590.
Newall F, Barnes C, Ignjatovic V, Monagle P. Heparin-induced thrombocytopenia in children. Journal of Paediatrics and Child Health. 2003;39(4):289-292. https://doi.org/10.1046/j.1440-1754.2003.00139.x
Massicotte P, Julian JA, Gent M, Shields K, Marzinotto V, Szechtman B, Andrew M; 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. Thrombosis Research. 2003;109(2-3):85-92. https://doi.org/10.1016/s0049-3848(03)00059-8
Dix D, Andrew M, Marzinotto V, Charpentier K, Bridge S, Monagle P, deVeber G, Leaker M, Chan AK, Massicotte MP. The use of low molecular weight heparin in pediatric patients: A prospective cohort study. Journal of Pediatrics. 2000;136(4):439-445. https://doi.org/10.1016/s0022-3476(00)90005-2
Kalaska B, Miklosz J, Kamiński K, Swieton J, Jakimczuk A, Yusa SI, Pawlak D, Nowakowska M, Szczubiałka K, Mogielnicki A. Heparin-binding copolymer as a complete antidote for low-molecular-weight heparins in rats. Journal of Pharmacology and Experimental Therapeutics. 2020;373(1):51-61. https://doi.org/10.1124/jpet.119.262931
Sol J, Boerma M, Klaassen I, Simons S, Witjes B, Wildschut E, Reiss I, van Ommen CH. Effectiveness and safety of nadroparin therapy in preterm and term neonates with venous thromboembolism. Journal of Clinical Medicine. 2021;10(7):1483. https://doi.org/10.3390/jcm10071483