Download PDF
Semin Thromb Hemost 2016; 42(07): 752-759
DOI: 10.1055/s-0036-1592299
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Developmental Hemostasis and Management of Central Venous Catheter Thrombosis in Neonates

C. Heleen van Ommen
1   Department of Pediatric Hematology, Erasmus MC Sophia Children's Hospital, Rotterdam, The Netherlands
,
Jeanine J. Sol
2   Department of Pediatrics, Groene Hart Hospital, Gouda, The Netherlands
› Author Affiliations
Further Information

Publication History

Publication Date:
16 September 2016 (online)

    Permissions and Reprints

Abstract

Neonatal hemostasis differs qualitatively, but in particular quantitatively, from hemostasis in older children and adults. Nevertheless, hemostasis in healthy neonates is functionally stable with no tendency to bleeding or thrombotic complications. In sick neonates, however, risk factors may disrupt this equilibrium and lead to thrombosis. The most important risk factor is the central venous catheter. Management of neonatal central venous catheter thrombosis is challenging, as no controlled trials have been performed. Therapeutic options include (1) observation and supportive treatment; (2) anticoagulant agents, including low-molecular-weight heparin and unfractionated heparin; (3) thrombolytic agents; and (4) thrombectomy. Prevention of thrombosis with anticoagulation is not advised yet. Careful consideration of the necessity of the catheter and optimal hygienic care are important preventative measures.

Keywords

central venous catheter - neonate - venous thrombosis - developmental hemostasis
 

  • References

  • 1 Manco-Johnson MJ. Development of hemostasis in the fetus. Thromb Res 2005; 115 (Suppl. 01) 55-63
    PubMedGoogle Scholar
  • 2 Wiedmeier SE, Henry E, Sola-Visner MC, Christensen RD. Platelet reference ranges for neonates, defined using data from over 47,000 patients in a multihospital healthcare system. J Perinatol 2009; 29 (2) 130-136
    CrossrefPubMedGoogle Scholar
  • 3 Israels SJ. Diagnostic evaluation of platelet function disorders in neonates and children: an update. Semin Thromb Hemost 2009; 35 (2) 181-188
    Article in Thieme ConnectPubMedGoogle Scholar
  • 4 Andrew M, Paes B, Bowker J, Vegh P. Evaluation of an automated bleeding time device in the newborn. Am J Hematol 1990; 35 (4) 275-277
    CrossrefPubMedGoogle Scholar
  • 5 Israels SJ, Cheang T, McMillan-Ward EM, Cheang M. Evaluation of primary hemostasis in neonates with a new in vitro platelet function analyzer. J Pediatr 2001; 138 (1) 116-119
    CrossrefPubMedGoogle Scholar
  • 6 Roschitz B, Sudi K, Köstenberger M, Muntean W. Shorter PFA-100 closure times in neonates than in adults: role of red cells, white cells, platelets and von Willebrand factor. Acta Paediatr 2001; 90 (6) 664-670
    PubMedGoogle Scholar
  • 7 Andrew M, Paes B, Milner R , et al. Development of the human coagulation system in the full-term infant. Blood 1987; 70 (1) 165-172
    PubMedGoogle Scholar
  • 8 Del Vecchio A, Latini G, Henry E, Christensen RD. Template bleeding times of 240 neonates born at 24 to 41 weeks gestation. J Perinatol 2008; 28 (6) 427-431
    CrossrefPubMedGoogle Scholar
  • 9 Katz JA, Moake JL, McPherson PD , et al. Relationship between human development and disappearance of unusually large von Willebrand factor multimers from plasma. Blood 1989; 73 (7) 1851-1858
    PubMedGoogle Scholar
  • 10 Sola-Visner MC, Christensen RD, Hutson AD, Rimsza LM. Megakaryocyte size and concentration in the bone marrow of thrombocytopenic and nonthrombocytopenic neonates. Pediatr Res 2007; 61 (4) 479-484
    CrossrefPubMedGoogle Scholar
  • 11 Ferrer-Marin F, Chavda C, Lampa M, Michelson AD, Frelinger III AL, Sola-Visner M. Effects of in vitro adult platelet transfusions on neonatal hemostasis. J Thromb Haemost 2011; 9 (5) 1020-1028
    CrossrefPubMedGoogle Scholar
  • 12 Attard C, van der Straaten T, Karlaftis V, Monagle P, Ignjatovic V. Developmental hemostasis: age-specific differences in the levels of hemostatic proteins. J Thromb Haemost 2013; 11 (10) 1850-1854
    PubMedGoogle Scholar
  • 13 Andrew M, Paes B, Milner R , et al. Development of the human coagulation system in the healthy premature infant. Blood 1988; 72 (5) 1651-1657
    PubMedGoogle Scholar
  • 14 Monagle P, Barnes C, Ignjatovic V , et al. Developmental haemostasis. Impact for clinical haemostasis laboratories. Thromb Haemost 2006; 95 (2) 362-372
    Article in Thieme ConnectPubMedGoogle Scholar
  • 15 van Teunenbroek A, Peters M, Sturk A, Borm JJ, Breederveld C. Protein C activity and antigen levels in childhood. Eur J Pediatr 1990; 149 (11) 774-778
    CrossrefPubMedGoogle Scholar
  • 16 Mulloy B, Hogwood J, Gray E, Lever R, Page CP. Pharmacology of heparin and related drugs. Pharmacol Rev 2016; 68 (1) 76-141
    PubMedGoogle Scholar
  • 17 Diaz R, Moffett BS, Karabinas S, Guffrey D, Mahoney Jr DH, Yee DL. Antithrombin concentrate use in children receiving unfractionated heparin for acute thrombosis. J Pediatr 2015; 167 (3) 645-649
    CrossrefPubMedGoogle Scholar
  • 18 Ryerson LM, Bauman ME, Kuhle S, Bruce AA, Massicotte MP. Antithrombin concentrate in pediatric patients requiring unfractionated heparin anticoagulation: a retrospective cohort study. Pediatr Crit Care Med 2014; 15 (8) e340-e346
    CrossrefPubMedGoogle Scholar
  • 19 Albisetti M. The fibrinolytic system in children. Semin Thromb Hemost 2003; 29 (4) 339-348
    Article in Thieme ConnectPubMedGoogle Scholar
  • 20 Andrew M, Brooker L, Leaker M, Paes B, Weitz J. Fibrin clot lysis by thrombolytic agents is impaired in newborns due to a low plasminogen concentration. Thromb Haemost 1992; 68 (3) 325-330
    PubMedGoogle Scholar
  • 21 Ries M, Zenker M, Klinge J, Keuper H, Harms D. Age-related differences in a clot lysis assay after adding different plasminogen activators in a plasma milieu in vitro. J Pediatr Hematol Oncol 1995; 17 (3) 260-264
    CrossrefPubMedGoogle Scholar
  • 22 Schmidt B, Andrew M. Neonatal thrombosis: report of a prospective Canadian and international registry. Pediatrics 1995; 96 (5, Pt 1): 939-943
    PubMedGoogle Scholar
  • 23 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
    CrossrefPubMedGoogle Scholar
  • 24 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 (5) 1251-1257
    CrossrefPubMedGoogle Scholar
  • 25 van Ommen CH, Heijboer H, van den Dool EJ, Hutten BA, Peters M. Pediatric venous thromboembolic disease in one single center: congenital prothrombotic disorders and the clinical outcome. J Thromb Haemost 2003; 1 (12) 2516-2522
    CrossrefPubMedGoogle Scholar
  • 26 Amankwah EK, Atchison CM, Arlikar S , et al. Risk factors for hospital-associated venous thromboembolism in the neonatal intensive care unit. Thromb Res 2014; 134 (2) 305-309
    CrossrefPubMedGoogle Scholar
  • 27 Kim JH, Lee YS, Kim SH, Lee SK, Lim MK, Kim HS. Does umbilical vein catheterization lead to portal venous thrombosis? Prospective US evaluation in 100 neonates. Radiology 2001; 219 (3) 645-650
    CrossrefPubMedGoogle Scholar
  • 28 Narang S, Roy J, Stevens TP, Butler-O'Hara M, Mullen CA, D'Angio CT. Risk factors for umbilical venous catheter-associated thrombosis in very low birth weight infants. Pediatr Blood Cancer 2009; 52 (1) 75-79
    CrossrefPubMedGoogle Scholar
  • 29 Young G, Albisetti M, Bonduel M , et al. Impact of inherited thrombophilia on venous thromboembolism in children: a systematic review and meta-analysis of observational studies. Circulation 2008; 118 (13) 1373-1382
    CrossrefPubMedGoogle Scholar
  • 30 Salonvaara M, Riikonen P, Kekomäki R, Heinonen K. Clinically symptomatic central venous catheter-related deep venous thrombosis in newborns. Acta Paediatr 1999; 88 (6) 642-646
    CrossrefPubMedGoogle Scholar
  • 31 Turebylu R, Salis R, Erbe R, Martin D, Lakshminrusimha S, Ryan RM. Genetic prothrombotic mutations are common in neonates but are not associated with umbilical catheter-associated thrombosis. J Perinatol 2007; 27 (8) 490-495
    CrossrefPubMedGoogle Scholar
  • 32 Demirel N, Aydin M, Zenciroglu A , et al. Neonatal thrombo-embolism: risk factors, clinical features and outcome. Ann Trop Paediatr 2009; 29 (4) 271-279
    CrossrefPubMedGoogle Scholar
  • 33 Park CK, Paes BA, Nagel K, Chan AK, Murthy P ; Thrombosis and Hemostasis in Newborns (THiN) Group. Neonatal central venous catheter thrombosis: diagnosis, management and outcome. Blood Coagul Fibrinolysis 2014; 25 (2) 97-106
    CrossrefPubMedGoogle Scholar
  • 34 Foo R, Fujii A, Harris JA, LaMorte W, Moulton S. Complications in tunneled CVL versus PICC lines in very low birth weight infants. J Perinatol 2001; 21 (8) 525-530
    CrossrefPubMedGoogle Scholar
  • 35 Pippus KG, Giacomantonio JM, Gillis DA, Rees EP. Thrombotic complications of saphenous central venous lines. J Pediatr Surg 1994; 29 (9) 1218-1219
    CrossrefPubMedGoogle Scholar
  • 36 Grisoni ER, Mehta SK, Connors AF. Thrombosis and infection complicating central venous catheterization in neonates. J Pediatr Surg 1986; 21 (9) 772-776
    CrossrefPubMedGoogle Scholar
  • 37 Wever ML, Liem KD, Geven WB, Tanke RB. Urokinase therapy in neonates with catheter related central venous thrombosis. Thromb Haemost 1995; 73 (2) 180-185
    PubMedGoogle Scholar
  • 38 Morag I, Epelman M, Daneman A , et al. Portal vein thrombosis in the neonate: risk factors, course, and outcome. J Pediatr 2006; 148 (6) 735-739
    CrossrefPubMedGoogle Scholar
  • 39 Williams S, Chan AK. Neonatal portal vein thrombosis: diagnosis and management. Semin Fetal Neonatal Med 2011; 16 (6) 329-339
    CrossrefPubMedGoogle Scholar
  • 40 Roy M, Turner-Gomes S, Gill G, Way C, Mernagh J, Schmidt B. Accuracy of Doppler echocardiography for the diagnosis of thrombosis associated with umbilical venous catheters. J Pediatr 2002; 140 (1) 131-134
    CrossrefPubMedGoogle Scholar
  • 41 Monagle P, Chan AK, Goldenberg NA , et al; American College of Chest Physicians. 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
    CrossrefPubMedGoogle Scholar
  • 42 Butler-O'Hara M, Buzzard CJ, Reubens L, McDermott MP, DiGrazio W, D'Angio CT. A randomized trial comparing long-term and short-term use of umbilical venous catheters in premature infants with birth weights of less than 1251 grams. Pediatrics 2006; 118 (1) e25-e35
    CrossrefPubMedGoogle Scholar
  • 43 van Elteren HA, Veldt HS, Te Pas AB , et al. Management and outcome in 32 neonates with thrombotic events. Int J Pediatr 2011; 2011: 217564
    PubMedGoogle Scholar
  • 44 Yang JY, Williams S, Brandão LR, Chan AK. Neonatal and childhood right atrial thrombosis: recognition and a risk-stratified treatment approach. Blood Coagul Fibrinolysis 2010; 21 (4) 301-307
    CrossrefPubMedGoogle Scholar
  • 45 Filippi L, Palermo L, Pezzati M , et al. Paradoxical embolism in a preterm infant. Dev Med Child Neurol 2004; 46 (10) 713-716
    PubMedGoogle Scholar
  • 46 Manco-Johnson MJ. How I treat venous thrombosis in children. Blood 2006; 107 (1) 21-29
    CrossrefPubMedGoogle Scholar
  • 47 Malowany JI, Monagle P, Knoppert DC , et al; Canadian Paediatric Thrombosis and Hemostasis Network. Enoxaparin for neonatal thrombosis: a call for a higher dose for neonates. Thromb Res 2008; 122 (6) 826-830
    CrossrefPubMedGoogle Scholar
  • 48 Schloemer NJ, Abu-Sultaneh S, Hanson SJ , et al. Higher doses of low-molecular-weight heparin (enoxaparin) are needed to achieve target anti-Xa concentrations in critically ill children. Pediatr Crit Care Med 2014; 15 (7) e294-e299
    CrossrefPubMedGoogle Scholar
  • 49 Chander A, Nagel K, Wiernikowski J, Paes B, Chan AK ; Thrombosis and Hemostasis in Newborns (THiN) Group. Evaluation of the use of low-molecular-weight heparin in neonates: a retrospective, single-center study. Clin Appl Thromb Hemost 2013; 19 (5) 488-493
    CrossrefPubMedGoogle Scholar
  • 50 Lulic-Botica M, Rajpurkar M, Sabo C, Tutag-Lehr V, Natarajan G. Fluctuations of anti-Xa concentrations during maintenance enoxaparin therapy for neonatal thrombosis. Acta Paediatr 2012; 101 (4) e147-e150
    CrossrefPubMedGoogle Scholar
  • 51 Hicks JK, Shelton CM, Sahni JK, Christensen ML. Retrospective evaluation of enoxaparin dosing in patients 48 weeks' postmenstrual age or younger in a neonatal intensive care unit. Ann Pharmacother 2012; 46 (7–8) 943-951
    CrossrefPubMedGoogle Scholar
  • 52 Fung LS, Klockau C. Effects of age and weight-based dosing of enoxaparin on anti-factor Xa levels in pediatric patients. J Pediatr Pharmacol Ther 2010; 15 (2) 119-125
    PubMedGoogle Scholar
  • 53 Ignjatovic V, Najid S, Newall F, Summerhayes R, Monagle P. Dosing and monitoring of enoxaparin (low molecular weight heparin) therapy in children. Br J Haematol 2010; 149 (5) 734-738
    CrossrefPubMedGoogle Scholar
  • 54 Sanchez de Toledo J, Gunawardena S, Munoz R , et al. Do neonates, infants and young children need a higher dose of enoxaparin in the cardiac intensive care unit?. Cardiol Young 2010; 20 (2) 138-143
    CrossrefPubMedGoogle Scholar
  • 55 Andrew M, Marzinotto V, Massicotte P , et al. Heparin therapy in pediatric patients: a prospective cohort study. Pediatr Res 1994; 35 (1) 78-83
    CrossrefPubMedGoogle Scholar
  • 56 Wang M, Hays T, Balasa V , et al; Pediatric Coagulation Consortium. Low-dose tissue plasminogen activator thrombolysis in children. J Pediatr Hematol Oncol 2003; 25 (5) 379-386
    CrossrefPubMedGoogle Scholar
  • 57 Corder A, Held K, Oschman A. Retrospective evaluation of antithrombin III supplementation in neonates and infants receiving enoxaparin for treatment of thrombosis. Pediatr Blood Cancer 2014; 61 (6) 1063-1067
    CrossrefPubMedGoogle Scholar
  • 58 Kuhle S, Eulmesekian P, Kavanagh B , et al. Lack of correlation between heparin dose and standard clinical monitoring tests in treatment with unfractionated heparin in critically ill children. Haematologica 2007; 92 (4) 554-557
    CrossrefPubMedGoogle Scholar
  • 59 Schechter T, Finkelstein Y, Ali M , et al. Unfractionated heparin dosing in young infants: clinical outcomes in a cohort monitored with anti-factor Xa levels. J Thromb Haemost 2012; 10 (3) 368-374
    CrossrefPubMedGoogle Scholar
  • 60 Bose J, Clarke P. Use of tissue plasminogen activator to treat intracardiac thrombosis in extremely low-birth-weight infants. Pediatr Crit Care Med 2011; 12 (6) e407-e409
    CrossrefPubMedGoogle Scholar
  • 61 Torres-Valdivieso MJ, Cobas J, Barrio C , et al. Successful use of tissue plasminogen activator in catheter-related intracardiac thrombus of a premature infant. Am J Perinatol 2003; 20 (2) 91-96
    Article in Thieme ConnectPubMedGoogle Scholar
  • 62 Dittrich S, Schlensak C, Kececioglu D. Successful thrombectomy of the superior vena cava thrombosis in a newborn after cardiopulmonary bypass surgery. Interact Cardiovasc Thorac Surg 2003; 2 (4) 692-693
    CrossrefPubMedGoogle Scholar
  • 63 Yang JY, Williams S, Brandão LR, Chan AK, Mondal T. Neonatal and childhood right atrial thrombosis: critical clot size. Blood Coagul Fibrinolysis 2013; 24 (4) 458
    PubMedGoogle Scholar
  • 64 Shah PS, Kalyn A, Satodia P , et al. A randomized, controlled trial of heparin versus placebo infusion to prolong the usability of peripherally placed percutaneous central venous catheters (PCVCs) in neonates: the HIP (Heparin Infusion for PCVC) study. Pediatrics 2007; 119 (1) e284-e291
    CrossrefPubMedGoogle Scholar
  • 65 Shah PS, Shah VS. Continuous heparin infusion to prevent thrombosis and catheter occlusion in neonates with peripherally placed percutaneous central venous catheters. Cochrane Database Syst Rev 2008; 1 (2) CD002772
    PubMedGoogle Scholar
  • 66 Shah PS, Shah N. Heparin-bonded catheters for prolonging the patency of central venous catheters in children. Cochrane Database Syst Rev 2014; 2 (2) CD005983
    PubMedGoogle Scholar
  • 67 Sneath N. Are supine chest and abdominal radiographs the best way to confirm PICC placement in neonates?. Neonatal Netw 2010; 29 (1) 23-35
    CrossrefPubMedGoogle Scholar
  • 68 Thornburg CD, Smith PB, Smithwick ML, Cotten CM, Benjamin Jr DK. Association between thrombosis and bloodstream infection in neonates with peripherally inserted catheters. Thromb Res 2008; 122 (6) 782-785
    CrossrefPubMedGoogle Scholar