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Venous thrombosis and thromboembolism in infants and children: Risk factors and clinical manifestations

Manuela Albisetti, MD
Anthony KC Chan, MBBS, FRCPC, FRCPath
Section Editor
Donald H Mahoney, Jr, MD
Deputy Editor
Carrie Armsby, MD, MPH


Although the incidence of venous thromboembolism (VTE) during childhood is remarkably lower than that seen in adults, VTE is increasingly recognized in the pediatric population as a complication of improved treatment strategies for previously lethal childhood diseases. This review summarizes the available information on the incidence, pathogenesis, and clinical manifestation of VTE in children beyond the neonatal period, excluding the central nervous system.

Diagnostic and therapeutic strategies for VTE in infants and children are discussed separately. VTE in the newborn is also discussed separately. (See "Diagnosis and treatment of venous thrombosis and thromboembolism in infants and children" and "Pathogenesis, clinical features, and diagnosis of thrombosis in the newborn" and "Management of thrombosis in the newborn".)


The incidence of VTE in children is not precisely known because only a few prospective studies of this subject exist [1,2]. In a first analysis of Canadian registry data, the incidence of documented VTE in the upper or lower venous system was 5.3 per 10,000 hospital admissions or 0.07 per 10,000 children aged 1 month to 18 years, with a peak incidence in infants younger than 1 year of age, and a mortality rate of 2.2 percent [1]. The mortality rate was predominantly due to associated conditions, which were identified in 96 percent of children; a central (indwelling) venous line was the single most important predisposing factor for VTE, being present in 33 percent of cases.

The annual rate of VTE in children in the United States, calculated from data from the National Hospital Discharge Survey (1979-2001), was 0.49 per 10,000 children per year [3]. The rate of diagnosis was higher in children younger than 2 years and in those older than 15 years compared with those between 2 and 14 years of age (1.05, 1.14, and 0.24/10,000 children per year, respectively). In teenagers, but not in younger children, the rate was greater in girls than boys (1.49 versus 0.81/10,000 children per year) and pregnancy accounted for the difference. For all age groups, the rate of VTE was approximately two times greater among blacks than whites.

A study that sampled more tertiary care hospitals in the United States reported substantially higher rates of VTE and that rates rose from 34 cases per 10,000 children in 2001 to 58 per 10,000 children in 2007 [4]. This represents a 70 percent increase in the diagnosis of VTE over the seven-year study period. The study was not able to determine whether this increase was due to a true increase in the frequency of VTE versus an increase in the detection of previously undiagnosed VTE, and did not have information about the proportion of VTE that were associated with central venous catheters (CVC). A separate study reported similar rates in freestanding children’s hospitals (40 per 10,000), and much lower rates in community hospitals (7.9 per 10,000); nearly 80 percent of the episodes of VTE were associated with an underlying chronic condition [5].


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Literature review current through: Jul 2017. | This topic last updated: Nov 17, 2016.
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  1. Andrew M, David M, Adams M, et al. Venous thromboembolic complications (VTE) in children: first analyses of the Canadian Registry of VTE. Blood 1994; 83:1251.
  2. van Ommen CH, Heijboer H, Büller HR, et al. Venous thromboembolism in childhood: a prospective two-year registry in The Netherlands. J Pediatr 2001; 139:676.
  3. Stein PD, Kayali F, Olson RE. Incidence of venous thromboembolism in infants and children: data from the National Hospital Discharge Survey. J Pediatr 2004; 145:563.
  4. 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; 124:1001.
  5. 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; 59:258.
  6. 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.
  7. Virchow, R. Phlogose und Thrombose im Gefässsystem. In: Gesammelte Abhandlungen zur Wissenschaftlichen Medizin, Virchow, R (Ed), Frankfurt 1856. p.458.
  8. Kuhle S, Massicotte P, Chan A, et al. Systemic thromboembolism in children. Data from the 1-800-NO-CLOTS Consultation Service. Thromb Haemost 2004; 92:722.
  9. Massicotte MP, Dix D, Monagle P, et al. Central venous catheter related thrombosis in children: analysis of the Canadian Registry of Venous Thromboembolic Complications. J Pediatr 1998; 133:770.
  10. Worly JM, Fortenberry JD, Hansen I, et al. Deep venous thrombosis in children with diabetic ketoacidosis and femoral central venous catheters. Pediatrics 2004; 113:e57.
  11. Menéndez JJ, Verdú C, Calderón B, et al. Incidence and risk factors of superficial and deep vein thrombosis associated with peripherally inserted central catheters in children. J Thromb Haemost 2016; 14:2158.
  12. Male C, Chait P, Ginsberg JS, et al. Comparison of venography and ultrasound for the diagnosis of asymptomatic deep vein thrombosis in the upper body in children: results of the PARKAA study. Prophylactic Antithrombin Replacement in Kids with ALL treated with Asparaginase. Thromb Haemost 2002; 87:593.
  13. Middeldorp S, Henkens CM, Koopman MM, et al. The incidence of venous thromboembolism in family members of patients with factor V Leiden mutation and venous thrombosis. Ann Intern Med 1998; 128:15.
  14. Simioni P, Sanson BJ, Prandoni P, et al. Incidence of venous thromboembolism in families with inherited thrombophilia. Thromb Haemost 1999; 81:198.
  15. Kosch A, Koch HG, Heinecke A, et al. Increased fasting total homocysteine plasma levels as a risk factor for thromboembolism in children. Thromb Haemost 2004; 91:308.
  16. Chalmers EA. Heritable thrombophilia and childhood thrombosis. Blood Rev 2001; 15:181.
  17. Tormene D, Simioni P, Prandoni P, et al. The incidence of venous thromboembolism in thrombophilic children: a prospective cohort study. Blood 2002; 100:2403.
  18. Nowak-Göttl U, Dübbers A, Kececioglu D, et al. Factor V Leiden, protein C, and lipoprotein (a) in catheter-related thrombosis in childhood: a prospective study. J Pediatr 1997; 131:608.
  19. Bonduel M, Hepner M, Sciuccati G, et al. Prothrombotic abnormalities in children with venous thromboembolism. J Pediatr Hematol Oncol 2000; 22:66.
  20. Bonduel M, Hepner M, Sciuccati G, et al. Factor V Leiden and prothrombin gene G20210A mutation in children with venous thromboembolism. Thromb Haemost 2002; 87:972.
  21. Lawson SE, Butler D, Enayat MS, Williams MD. Congenital thrombophilia and thrombosis: a study in a single centre. Arch Dis Child 1999; 81:176.
  22. van Ommen CH, Peters M. Venous thromboembolic disease in childhood. Semin Thromb Hemost 2003; 29:391.
  23. van Ommen CH, Heijboer H, van den Dool EJ, et al. Pediatric venous thromboembolic disease in one single center: congenital prothrombotic disorders and the clinical outcome. J Thromb Haemost 2003; 1:2516.
  24. Revel-Vilk S, Chan A, Bauman M, Massicotte P. Prothrombotic conditions in an unselected cohort of children with venous thromboembolic disease. J Thromb Haemost 2003; 1:915.
  25. Neshat-Vahid S, Pierce R, Hersey D, et al. Association of thrombophilia and catheter-associated thrombosis in children: a systematic review and meta-analysis. J Thromb Haemost 2016; 14:1749.
  26. 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; 118:1373.
  27. Andrew M, Vegh P, Johnston M, et al. Maturation of the hemostatic system during childhood. Blood 1992; 80:1998.
  28. Massicotte P, Leaker M, Marzinotto V, et al. Enhanced thrombin regulation during warfarin therapy in children compared to adults. Thromb Haemost 1998; 80:570.
  29. Mitchell L, Piovella F, Ofosu F, Andrew M. Alpha-2-macroglobulin may provide protection from thromboembolic events in antithrombin III-deficient children. Blood 1991; 78:2299.
  30. Manco-Johnson MJ. Neonatal antithrombin III deficiency. Am J Med 1989; 87:49S.
  31. Thompson AJ, McSwain SD, Webb SA, et al. Venous thromboembolism prophylaxis in the pediatric trauma population. J Pediatr Surg 2013; 48:1413.
  32. Van Arendonk KJ, Schneider EB, Haider AH, et al. Venous thromboembolism after trauma: when do children become adults? JAMA Surg 2013; 148:1123.
  33. Allen CJ, Murray CR, Meizoso JP, et al. Risk factors for venous thromboembolism after pediatric trauma. J Pediatr Surg 2016; 51:168.
  34. Nguyen GC, Bernstein CN, Bitton A, et al. Consensus statements on the risk, prevention, and treatment of venous thromboembolism in inflammatory bowel disease: Canadian Association of Gastroenterology. Gastroenterology 2014; 146:835.
  35. Levy DM, Massicotte MP, Harvey E, et al. Thromboembolism in paediatric lupus patients. Lupus 2003; 12:741.
  36. Nowak-Göttl U, Junker R, Kreuz W, et al. Risk of recurrent venous thrombosis in children with combined prothrombotic risk factors. Blood 2001; 97:858.
  37. Goldenberg NA, Knapp-Clevenger R, Manco-Johnson MJ, Mountain States Regional Thrombophilia Group. Elevated plasma factor VIII and D-dimer levels as predictors of poor outcomes of thrombosis in children. N Engl J Med 2004; 351:1081.
  38. Monagle P, Adams M, Mahoney M, et al. Outcome of pediatric thromboembolic disease: a report from the Canadian Childhood Thrombophilia Registry. Pediatr Res 2000; 47:763.
  39. Journeycake JM, Buchanan GR. Catheter-related deep venous thrombosis and other catheter complications in children with cancer. J Clin Oncol 2006; 24:4575.
  40. Marie I, Lévesque H, Cailleux N, et al. [Deep venous thrombosis of the upper limbs. Apropos of 49 cases]. Rev Med Interne 1998; 19:399.
  41. Mulvihill SJ, Fonkalsrud EW. Complications of superior versus inferior vena cava occlusion in infants receiving central total parenteral nutrition. J Pediatr Surg 1984; 19:752.
  42. Rockoff MA, Gang DL, Vacanti JP. Fatal pulmonary embolism following removal of a central venous catheter. J Pediatr Surg 1984; 19:307.
  43. Derish MT, Smith DW, Frankel LR. Venous catheter thrombus formation and pulmonary embolism in children. Pediatr Pulmonol 1995; 20:349.
  44. Byard RW, Cutz E. Sudden and unexpected death in infancy and childhood due to pulmonary thromboembolism. An autopsy study. Arch Pathol Lab Med 1990; 114:142.
  45. Matthew DJ, Levin M. Pulmonary thromboembolism in children. Intensive Care Med 1986; 12:404.
  46. Agha BS, Sturm JJ, Simon HK, Hirsh DA. Pulmonary embolism in the pediatric emergency department. Pediatrics 2013; 132:663.
  47. Andrew, M, Monagle, P, Brooker, LA. Thromboembolic complications during infancy and childhood. BC Decker Inc, Hamilton, Ontario 2000.
  48. Bernstein D, Coupey S, Schonberg SK. Pulmonary embolism in adolescents. Am J Dis Child 1986; 140:667.
  49. Buck JR, Connors RH, Coon WW, et al. Pulmonary embolism in children. J Pediatr Surg 1981; 16:385.
  50. Goldsby RE, Saulys AJ, Helton JG. Pediatric pulmonary artery thromboembolism: an illustrative case. Pediatr Emerg Care 1996; 12:105.
  51. Biss TT, Brandão LR, Kahr WH, et al. Clinical features and outcome of pulmonary embolism in children. Br J Haematol 2008; 142:808.
  52. Biss TT, Brandão LR, Kahr WH, et al. Clinical probability score and D-dimer estimation lack utility in the diagnosis of childhood pulmonary embolism. J Thromb Haemost 2009; 7:1633.
  53. Brandão LR, Simpson EA, Lau KK. Neonatal renal vein thrombosis. Semin Fetal Neonatal Med 2011; 16:323.
  54. Tinaztepe K, Buyan N, Tinaztepe B, Akkök N. The association of nephrotic syndrome and renal vein thrombosis: a clinicopathological analysis of eight pediatric patients. Turk J Pediatr 1989; 31:1.
  55. Chugh KS, Malik N, Uberoi HS, et al. Renal vein thrombosis in nephrotic syndrome--a prospective study and review. Postgrad Med J 1981; 57:566.
  56. Waymack JP, Tweddell JS, Warden GD. Renal vein thrombosis in burned children. J Burn Care Rehabil 1988; 9:472.
  57. Asherson RA, Lanham JG, Hull RG, et al. Renal vein thrombosis in systemic lupus erythematosus: association with the "lupus anticoagulant". Clin Exp Rheumatol 1984; 2:75.
  58. Harmon WE, Stablein D, Alexander SR, Tejani A. Graft thrombosis in pediatric renal transplant recipients. A report of the North American Pediatric Renal Transplant Cooperative Study. Transplantation 1991; 51:406.
  59. Williams S, Chan AK. Neonatal portal vein thrombosis: diagnosis and management. Semin Fetal Neonatal Med 2011; 16:329.
  60. Brady L, Magilavy D, Black DD. Portal vein thrombosis associated with antiphospholipid antibodies in a child. J Pediatr Gastroenterol Nutr 1996; 23:470.
  61. Arav-Boger R, Reif S, Bujanover Y. Portal vein thrombosis caused by protein C and protein S deficiency associated with cytomegalovirus infection. J Pediatr 1995; 126:586.
  62. Skarsgard E, Doski J, Jaksic T, et al. Thrombosis of the portal venous system after splenectomy for pediatric hematologic disease. J Pediatr Surg 1993; 28:1109.
  63. Arnold KE, Char G, Serjeant GR. Portal vein thrombosis in a child with homozygous sickle-cell disease. West Indian Med J 1993; 42:27.
  64. Harper PL, Edgar PF, Luddington RJ, et al. Protein C deficiency and portal thrombosis in liver transplantation in children. Lancet 1988; 2:924.
  65. Brisse H, Orbach D, Lassau N, et al. Portal vein thrombosis during antineoplastic chemotherapy in children: report of five cases and review of the literature. Eur J Cancer 2004; 40:2659.
  66. Stringer MD, Marshall MM, Muiesan P, et al. Survival and outcome after hepatic artery thrombosis complicating pediatric liver transplantation. J Pediatr Surg 2001; 36:888.
  67. Prandoni P, Lensing AW, Prins MR. The natural history of deep-vein thrombosis. Semin Thromb Hemost 1997; 23:185.
  68. Thulesius O. [The pathophysiology of post-thrombotic syndrome]. Wien Med Wochenschr 1994; 144:196.
  69. Immelman EJ, Jeffery PC. The postphlebitic syndrome. Pathophysiology, prevention and management. Clin Chest Med 1984; 5:537.
  70. Goldenberg NA, Brandão L, Journeycake J, et al. Definition of post-thrombotic syndrome following lower extremity deep venous thrombosis and standardization of outcome measurement in pediatric clinical investigations. J Thromb Haemost 2012; 10:477.
  71. Revel-Vilk S, Brandão LR, Journeycake J, et al. Standardization of post-thrombotic syndrome definition and outcome assessment following upper venous system thrombosis in pediatric practice. J Thromb Haemost 2012; 10:2182.
  72. Kuhle S, Koloshuk B, Marzinotto V, et al. A cross-sectional study evaluating post-thrombotic syndrome in children. Thromb Res 2003; 111:227.
  73. van Ommen CH, Ottenkamp J, Lam J, et al. The risk of postthrombotic syndrome in children with congenital heart disease. J Pediatr 2002; 141:582.
  74. Spentzouris G, Gasparis A, Scriven RJ, et al. Natural history of deep vein thrombosis in children. Phlebology 2015; 30:412.
  75. Avila ML, Pullenayegum E, Williams S, et al. Post-thrombotic syndrome and other outcomes of lower extremity deep vein thrombosis in children. Blood 2016.
  76. 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; 95:1952.
  77. Rajpurkar M, Sharathkumar A, Williams S, et al. Recommendations for the assessment of non-extremity venous thromboembolism outcomes: communication from the SSC of the ISTH. J Thromb Haemost 2015; 13:477.
  78. Manco-Johnson M, Knapp-Clevenger R, Miller B, et al. Post-thrombotic syndrome (PTS) in children: Validation of a new pediatric outcome instrument and results in a comprehensive cohort of children with extremity deep vein thrombosis (DVT). Blood 2003; 102:553a.
  79. Goldenberg NA, Pounder E, Knapp-Clevenger R, Manco-Johnson MJ. Validation of upper extremity post-thrombotic syndrome outcome measurement in children. J Pediatr 2010; 157:852.
  80. Holzhauer S, Goldenberg NA, Junker R, et al. Inherited thrombophilia in children with venous thromboembolism and the familial risk of thromboembolism: an observational study. Blood 2012; 120:1510.