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Management of thrombosis in the newborn

Anthony KC Chan, MBBS, FRCPC, FRCPath
Mihir D Bhatt, MD
Section Editors
Donald H Mahoney, Jr, MD
Joseph A Garcia-Prats, MD
Deputy Editor
Carrie Armsby, MD, MPH


Thrombotic disease is uncommon in newborns. However, this disorder can cause serious morbidity. The management of neonatal thrombosis, excluding the central nervous system (CNS), is reviewed here. The pathogenesis, clinical features, and diagnosis of this disorder and CNS thromboembolic disease are discussed separately. (See "Pathogenesis, clinical features, and diagnosis of thrombosis in the newborn" and "Stroke in the newborn: Classification, manifestations, and diagnosis".)


Newborns are at risk for thrombosis because of the unique characteristics of their coagulation and fibrinolytic system as compared with older age groups, and also because of triggers such as indwelling catheters. Because these risk factors usually are transient, the recurrence risk is low. Therefore, the primary goals of treatment in this age group is to prevent further extension of the clot, which can result in end-organ damage. Rarely, a neonate has a chronic condition that predisposes to thrombosis, such as neonatal purpura fulminans; in this case, long-term prophylaxis is needed. (See 'Neonatal purpura fulminans' below.)

The management of neonatal thrombosis is extrapolated largely from data in adults. Little information is available on management strategies or the efficacy and safety of therapeutic agents in the neonatal age group. The approach to an individual infant must balance the risks and benefits.

For asymptomatic thrombosis, we suggest supportive care and close monitoring of the size of the thrombus [1]. This approach avoids development of bleeding complications that may be associated with anticoagulant or fibrinolytic therapy. If the thrombus is associated with a central venous line (CVL) or umbilical venous catheter, the catheter should be removed. If the thrombus extends, we suggest treatment [1]. Alternatively, initial treatment with anticoagulant is a reasonable option, particularly when it is not feasible to remove the catheter due to the patient's clinical condition.

For symptomatic thrombosis, we suggest treatment with anticoagulation and/or fibrinolytic agents. However, these strategies have not been studied in clinical trials, and data on outcome in neonates are sparse [2,3]. The management of less severe events also is uncertain. CVLs or umbilical venous catheters associated with thrombosis should be removed, if possible, immediately or after three to five days of anticoagulation [1]. Though there is a theoretical risk of embolism with immediate catheter removal (ie, before anticoagulation), anecdotal evidence and clinical experience suggests this is uncommon. If a central catheter is still in place on completion of therapeutic anticoagulation, we suggest treatment with a prophylactic dose of low molecular weight heparin (LMWH) until the device is removed. (See 'Dose' below.)

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Literature review current through: Nov 2017. | This topic last updated: Nov 01, 2017.
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  1. Monagle P, Chan AK, 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:e737S.
  2. Edstrom CS, Christensen RD. Evaluation and treatment of thrombosis in the neonatal intensive care unit. Clin Perinatol 2000; 27:623.
  3. Dix D, Andrew M, Marzinotto V, et al. The use of low molecular weight heparin in pediatric patients: a prospective cohort study. J Pediatr 2000; 136:439.
  4. Bhatt MD, Paes BA, Chan AK. How to use unfractionated heparin to treat neonatal thrombosis in clinical practice. Blood Coagul Fibrinolysis 2016; 27:605.
  5. Lin PH, Dodson TF, Bush RL, et al. Surgical intervention for complications caused by femoral artery catheterization in pediatric patients. J Vasc Surg 2001; 34:1071.
  6. Hedrick M, Elkins RC, Knott-Craig CJ, Razook JD. Successful thrombectomy for thrombosis of the right side of the heart after the Fontan operation. Report of two cases and review of the literature. J Thorac Cardiovasc Surg 1993; 105:297.
  7. Weitz JI. Low-molecular-weight heparins. N Engl J Med 1997; 337:688.
  8. Albisetti M, Andrew M. Low molecular weight heparin in children. Eur J Pediatr 2002; 161:71.
  9. van der Heijden JF, Prins MH, Büller HR. For the initial treatment of venous thromboembolism: are all low-molecular-weight heparin compounds the same? Thromb Res 2000; 100:V121.
  10. Massicotte P, Adams M, Marzinotto V, et al. Low-molecular-weight heparin in pediatric patients with thrombotic disease: a dose finding study. J Pediatr 1996; 128:313.
  11. Nohe N, Flemmer A, Rümler R, et al. The low molecular weight heparin dalteparin for prophylaxis and therapy of thrombosis in childhood: a report on 48 cases. Eur J Pediatr 1999; 158 Suppl 3:S134.
  12. 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; 94:1164.
  13. van Ommen CH, van den Dool EJ, Peters M. Nadroparin therapy in pediatric patients with venous thromboembolic disease. J Pediatr Hematol Oncol 2008; 30:230.
  14. Malowany JI, Monagle P, Knoppert DC, et al. Enoxaparin for neonatal thrombosis: a call for a higher dose for neonates. Thromb Res 2008; 122:826.
  15. Cruickshank MK, Levine MN, Hirsh J, et al. A standard heparin nomogram for the management of heparin therapy. Arch Intern Med 1991; 151:333.
  16. Bauman ME, Black KL, Bauman ML, et al. Novel uses of insulin syringes to reduce dosing errors: a retrospective chart review of enoxaparin whole milligram dosing. Thromb Res 2009; 123:845.
  17. Chander A, Nagel K, Wiernikowski J, et al. Evaluation of the use of low-molecular-weight heparin in neonates: a retrospective, single-center study. Clin Appl Thromb Hemost 2013; 19:488.
  18. Crowther MA, Berry LR, Monagle PT, Chan AK. Mechanisms responsible for the failure of protamine to inactivate low-molecular-weight heparin. Br J Haematol 2002; 116:178.
  19. Evaluation of the Duration of Therapy for Thrombosis in Children (Kids-DOTT) https://clinicaltrials.gov/ct2/show/NCT00687882 (Accessed on October 13, 2016).
  20. Hirsh J, Bauer KA, Donati MB, et al. Parenteral anticoagulants: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133:141S.
  21. Patel S, Berry LR, Chan AK. Analysis of inhibition rate enhancement by covalent linkage of antithrombin to heparin as a potential predictor of reaction mechanism. J Biochem 2007; 141:25.
  22. Choay J, Petitou M, Lormeau JC, et al. Structure-activity relationship in heparin: a synthetic pentasaccharide with high affinity for antithrombin III and eliciting high anti-factor Xa activity. Biochem Biophys Res Commun 1983; 116:492.
  23. Danielsson A, Raub E, Lindahl U, Björk I. Role of ternary complexes, in which heparin binds both antithrombin and proteinase, in the acceleration of the reactions between antithrombin and thrombin or factor Xa. J Biol Chem 1986; 261:15467.
  24. Andrew M, Marzinotto V, Massicotte P, et al. Heparin therapy in pediatric patients: a prospective cohort study. Pediatr Res 1994; 35:78.
  25. Hanslik A, Kitzmüller E, Thom K, et al. Incidence of thrombotic and bleeding complications during cardiac catheterization in children: comparison of high-dose vs. low-dose heparin protocols. J Thromb Haemost 2011; 9:2353.
  26. Newall F, Johnston L, Ignjatovic V, Monagle P. Unfractionated heparin therapy in infants and children. Pediatrics 2009; 123:e510.
  27. Andrew M. Developmental hemostasis: relevance to thromboembolic complications in pediatric patients. Thromb Haemost 1995; 74:415.
  28. Schmidt B, Buchanan MR, Ofosu F, et al. Antithrombotic properties of heparin in a neonatal piglet model of thrombin-induced thrombosis. Thromb Haemost 1988; 60:289.
  29. 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; 10:368.
  30. Juergens CP, Semsarian C, Keech AC, et al. Hemorrhagic complications of intravenous heparin use. Am J Cardiol 1997; 80:150.
  31. Warkentin TE, Chong BH, Greinacher A. Heparin-induced thrombocytopenia: towards consensus. Thromb Haemost 1998; 79:1.
  32. 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; 332:1330.
  33. Demasi R, Bode AP, Knupp C, et al. Heparin-induced thrombocytopenia. Am Surg 1994; 60:26.
  34. Schmitt BP, Adelman B. Heparin-associated thrombocytopenia: a critical review and pooled analysis. Am J Med Sci 1993; 305:208.
  35. Visentin GP, Ford SE, Scott JP, Aster RH. Antibodies from patients with heparin-induced thrombocytopenia/thrombosis are specific for platelet factor 4 complexed with heparin or bound to endothelial cells. J Clin Invest 1994; 93:81.
  36. Ziporen L, Li ZQ, Park KS, et al. Defining an antigenic epitope on platelet factor 4 associated with heparin-induced thrombocytopenia. Blood 1998; 92:3250.
  37. Spadone D, Clark F, James E, et al. Heparin-induced thrombocytopenia in the newborn. J Vasc Surg 1992; 15:306.
  38. Ranze O, Ranze P, Magnani HN, Greinacher A. Heparin-induced thrombocytopenia in paediatric patients--a review of the literature and a new case treated with danaparoid sodium. Eur J Pediatr 1999; 158 Suppl 3:S130.
  39. Roy M, Turner-Gomes S, Gill G, et al. Accuracy of Doppler echocardiography for the diagnosis of thrombosis associated with umbilical venous catheters. J Pediatr 2002; 140:131.
  40. Andrew ME, Monagle P, deVeber G, Chan AK. Thromboembolic disease and antithrombotic therapy in newborns. Hematology Am Soc Hematol Educ Program 2001; :358.
  41. Young G. Old and new antithrombotic drugs in neonates and infants. Semin Fetal Neonatal Med 2011; 16:349.
  42. Risch L, Huber AR, Schmugge M. Diagnosis and treatment of heparin-induced thrombocytopenia in neonates and children. Thromb Res 2006; 118:123.
  43. Andrew M, Brooker L, Leaker M, et al. Fibrin clot lysis by thrombolytic agents is impaired in newborns due to a low plasminogen concentration. Thromb Haemost 1992; 68:325.
  44. Ries M, Easton RL, Longstaff C, et al. Differences between neonates and adults in tissue-type-plasminogen activator (t-PA)-catalyzed plasminogen activation with various effectors and in carbohydrate sequences of fibrinogen chains. Thromb Res 2001; 103:173.
  45. Manco-Johnson MJ, Grabowski EF, Hellgreen M, et al. Recommendations for tPA thrombolysis in children. On behalf of the Scientific Subcommittee on Perinatal and Pediatric Thrombosis of the Scientific and Standardization Committee of the International Society of Thrombosis and Haemostasis. Thromb Haemost 2002; 88:157.
  46. Stephens MB, Pepper PV. Streptokinase therapy. Recognizing and treating allergic reactions. Postgrad Med 1998; 103:89.
  47. Hartmann J, Hussein A, Trowitzsch E, et al. Treatment of neonatal thrombus formation with recombinant tissue plasminogen activator: six years experience and review of the literature. Arch Dis Child Fetal Neonatal Ed 2001; 85:F18.
  48. Farnoux C, Camard O, Pinquier D, et al. Recombinant tissue-type plasminogen activator therapy of thrombosis in 16 neonates. J Pediatr 1998; 133:137.
  49. Ferrari F, Vagnarelli F, Gargano G, et al. Early intracardiac thrombosis in preterm infants and thrombolysis with recombinant tissue type plasminogen activator. Arch Dis Child Fetal Neonatal Ed 2001; 85:F66.
  50. Gupta AA, Leaker M, Andrew M, et al. Safety and outcomes of thrombolysis with tissue plasminogen activator for treatment of intravascular thrombosis in children. J Pediatr 2001; 139:682.
  51. Nowak-Göttl U, Auberger K, Halimeh S, et al. Thrombolysis in newborns and infants. Thromb Haemost 1999; 82 Suppl 1:112.
  52. Leaker M, Massicotte MP, Brooker LA, Andrew M. Thrombolytic therapy in pediatric patients: a comprehensive review of the literature. Thromb Haemost 1996; 76:132.
  53. El-Segaier M, Khan MA, Khan ZU, et al. Recombinant Tissue Plasminogen Activator in the Treatment of Neonates with Intracardiac and Great Vessels Thrombosis. Pediatr Cardiol 2015; 36:1582.
  54. Andrew M. Society for Pediatric Research Presidential Address 1998: the SPR and 1-800-NO-CLOTS: a common vision. Pediatr Res 1998; 44:964.
  55. Lau KK, Stoffman JM, Williams S, et al. Neonatal renal vein thrombosis: review of the English-language literature between 1992 and 2006. Pediatrics 2007; 120:e1278.
  56. Messinger Y, Sheaffer JW, Mrozek J, et al. Renal outcome of neonatal renal venous thrombosis: review of 28 patients and effectiveness of fibrinolytics and heparin in 10 patients. Pediatrics 2006; 118:e1478.
  57. Tuckuviene R, Christensen AL, Helgestad J, et al. Pediatric venous and arterial noncerebral thromboembolism in Denmark: a nationwide population-based study. J Pediatr 2011; 159:663.
  58. Samama MM, Gerotziafas GT. Comparative pharmacokinetics of LMWHs. Semin Thromb Hemost 2000; 26 Suppl 1:31.
  59. 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; 21:301.
  60. Yang JY, Williams S, Brandão LR, et al. Neonatal and childhood right atrial thrombosis: critical clot size. Blood Coagul Fibrinolysis 2013; 24:458.
  61. Branson HE, Katz J, Marble R, Griffin JH. Inherited protein C deficiency and coumarin-responsive chronic relapsing purpura fulminans in a newborn infant. Lancet 1983; 2:1165.
  62. Marciniak E, Wilson HD, Marlar RA. Neonatal purpura fulminans: a genetic disorder related to the absence of protein C in blood. Blood 1985; 65:15.
  63. Yuen P, Cheung A, Lin HJ, et al. Purpura fulminans in a Chinese boy with congenital protein C deficiency. Pediatrics 1986; 77:670.
  64. Estellés A, Garcia-Plaza I, Dasí A, et al. Severe inherited "homozygous" protein C deficiency in a newborn infant. Thromb Haemost 1984; 52:53.
  65. Sills RH, Marlar RA, Montgomery RR, et al. Severe homozygous protein C deficiency. J Pediatr 1984; 105:409.
  66. Rappaport ES, Speights VO, Helbert B, et al. Protein C deficiency. South Med J 1987; 80:240.
  67. Fruchtman Y, Strauss T, Rubinstein M, et al. Skin Necrosis and Purpura Fulminans in Children With and Without Thrombophilia--A Tertiary Center's Experience. Pediatr Hematol Oncol 2015; 32:505.
  68. Marlar RA, Neumann A. Neonatal purpura fulminans due to homozygous protein C or protein S deficiencies. Semin Thromb Hemost 1990; 16:299.
  69. Vigano D'Angelo S, Comp PC, Esmon CT, D'Angelo A. Relationship between protein C antigen and anticoagulant activity during oral anticoagulation and in selected disease states. J Clin Invest 1986; 77:416.
  70. Viganò S, Mannucci PM, Solinas S, et al. Decrease in protein C antigen and formation of an abnormal protein soon after starting oral anticoagulant therapy. Br J Haematol 1984; 57:213.
  71. prescribing information for this product is available at the following website: http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=22370 (Accessed on November 17, 2011).
  72. Dreyfus M, Magny JF, Bridey F, et al. Treatment of homozygous protein C deficiency and neonatal purpura fulminans with a purified protein C concentrate. N Engl J Med 1991; 325:1565.
  73. Conard J, Bauer KA, Gruber A, et al. Normalization of markers of coagulation activation with a purified protein C concentrate in adults with homozygous protein C deficiency. Blood 1993; 82:1159.
  74. Price VE, Ledingham DL, Krümpel A, Chan AK. Diagnosis and management of neonatal purpura fulminans. Semin Fetal Neonatal Med 2011; 16:318.
  75. Mahasandana C, Suvatte V, Marlar RA, et al. Neonatal purpura fulminans associated with homozygous protein S deficiency. Lancet 1990; 335:61.
  76. Mahasandana C, Suvatte V, Chuansumrit A, et al. Homozygous protein S deficiency in an infant with purpura fulminans. J Pediatr 1990; 117:750.
  77. Martinelli I, Mannucci PM, De Stefano V, et al. Different risks of thrombosis in four coagulation defects associated with inherited thrombophilia: a study of 150 families. Blood 1998; 92:2353.
  78. Peters C, Casella JF, Marlar RA, et al. Homozygous protein C deficiency: observations on the nature of the molecular abnormality and the effectiveness of warfarin therapy. Pediatrics 1988; 81:272.
  79. Garcia-Plaza I, Jimenez-Astorga C, Borrego D, Marty ML. Coumarin prophylaxis for fulminant purpura syndrome due to homozygous protein C deficiency. Lancet 1985; 1:634.
  80. Hartman KR, Manco-Johnson M, Rawlings JS, et al. Homozygous protein C deficiency: early treatment with warfarin. Am J Pediatr Hematol Oncol 1989; 11:395.
  81. Monagle P, Andrew M, Halton J, et al. Homozygous protein C deficiency: description of a new mutation and successful treatment with low molecular weight heparin. Thromb Haemost 1998; 79:756.
  82. Minford AM, Parapia LA, Stainforth C, Lee D. Treatment of homozygous protein C deficiency with subcutaneous protein C concentrate. Br J Haematol 1996; 93:215.
  83. Sanz-Rodriguez C, Gil-Fernández JJ, Zapater P, et al. Long-term management of homozygous protein C deficiency: replacement therapy with subcutaneous purified protein C concentrate. Thromb Haemost 1999; 81:887.
  84. de Kort EH, Vrancken SL, van Heijst AF, et al. Long-term subcutaneous protein C replacement in neonatal severe protein C deficiency. Pediatrics 2011; 127:e1338.
  85. Mathias M, Khair K, Burgess C, Liesner R. Subcutaneous administration of protein C concentrate. Pediatr Hematol Oncol 2004; 21:551.
  86. Piccini B, Capirchio L, Lenzi L, et al. Continuous subcutaneous infusion of protein C concentrate using an insulin pump in a newborn with congenital protein C deficiency. Blood Coagul Fibrinolysis 2014; 25:522.
  87. Lee MJ, Kim KM, Kim JS, et al. Long-term survival of a child with homozygous protein C deficiency successfully treated with living donor liver transplantation. Pediatr Transplant 2009; 13:251.
  88. Angelis M, Pegelow CH, Khan FA, et al. En bloc heterotopic auxiliary liver and bilateral renal transplant in a patient with homozygous protein C deficiency. J Pediatr 2001; 138:120.
  89. Barrington KJ. Umbilical artery catheters in the newborn: effects of heparin. Cochrane Database Syst Rev 2000; :CD000507.
  90. Rais-Bahrami K, Karna P, Dolanski EA. Effect of fluids on life span of peripheral arterial lines. Am J Perinatol 1990; 7:122.
  91. Butt W, Shann F, McDonnell G, Hudson I. Effect of heparin concentration and infusion rate on the patency of arterial catheters. Crit Care Med 1987; 15:230.
  92. Randolph AG, Cook DJ, Gonzales CA, Andrew M. Benefit of heparin in peripheral venous and arterial catheters: systematic review and meta-analysis of randomised controlled trials. BMJ 1998; 316:969.
  93. Shah P, Shah V. Continuous heparin infusion to prevent thrombosis and catheter occlusion in neonates with peripherally placed percutaneous central venous catheters. Cochrane Database Syst Rev 2001; :CD002772.
  94. Lau KK, Chan HH, Massicotte P, Chan AK. Thrombotic complications of neonates and children with congenital nephrotic syndrome. Curr Pediatr Rev 2014; 10:169.
  95. Nowak-Göttl U, von Kries R, Göbel U. Neonatal symptomatic thromboembolism in Germany: two year survey. Arch Dis Child Fetal Neonatal Ed 1997; 76:F163.
  96. Schmidt B, Andrew M. Neonatal thrombosis: report of a prospective Canadian and international registry. Pediatrics 1995; 96:939.
  97. Kooiman AM, Kootstra G, Zwierstra RP. Portal hypertension in children due to thrombosis of the portal vein. Neth J Surg 1982; 34:97.
  98. Junker P, Egeblad M, Nielsen O, Kamper J. Umbilical vein catheterization and portal hypertension. Acta Paediatr Scand 1976; 65:499.
  99. Zigman A, Yazbeck S, Emil S, Nguyen L. Renal vein thrombosis: a 10-year review. J Pediatr Surg 2000; 35:1540.
  100. Marks SD, Massicotte MP, Steele BT, et al. Neonatal renal venous thrombosis: clinical outcomes and prevalence of prothrombotic disorders. J Pediatr 2005; 146:811.
  101. Winyard PJ, Bharucha T, De Bruyn R, et al. Perinatal renal venous thrombosis: presenting renal length predicts outcome. Arch Dis Child Fetal Neonatal Ed 2006; 91:F273.
  102. Barnes C, Newall F, Monagle P. Post-thrombotic syndrome. Arch Dis Child 2002; 86:212.