Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Screening for inherited thrombophilia in children

Leslie Raffini, MD
Section Editor
Donald H Mahoney, Jr, MD
Deputy Editor
Carrie Armsby, MD, MPH


Thrombotic events (venous thromboembolism [VTE] and stroke) in children have become increasingly recognized in pediatric tertiary care hospitals, although they are rare in healthy children [1]. Over the past several decades, numerous inherited risk factors for thrombosis have been identified, improving our understanding of the pathogenesis of venous thrombosis. The majority of children with VTE have multiple risk factors; the most common risk factor is the presence of a central (indwelling) venous catheter (CVC). Other risk factors include surgery, trauma, use of oral contraceptives, immobilization, infection, systemic lupus erythematosus, structural venous abnormalities, and cancer. (See "Venous thrombosis and thromboembolism in children: Risk factors, clinical manifestations, and diagnosis".)

While inherited prothrombotic disorders also contribute to the risk of VTE, the prevalence of these disorders varies considerably depending upon the specific patient population (eg, an underlying inherited thrombophilia [IT] is more likely to be found in an adolescent with an unprovoked VTE as compared with a neonate with CVC-related VTE). Because of this variation, the role of screening all children with VTE for IT has become more controversial. In addition, IT testing of otherwise healthy children who have a family history of thrombosis or thrombophilia has become more common. The clinical utility of performing such tests has been increasingly scrutinized, and it is important to understand the potential benefits and limitations of testing. Recommendations and rationale for thrombophilia testing in children who have had a thrombotic event as well as those who have a positive family history will be reviewed here, although this remains an area in which there is significant practice variation.

Screening for inherited thrombophilia in adults is discussed elsewhere:

Asymptomatic adults (eg, individuals with a family history of VTE) (see "Screening for inherited thrombophilia in asymptomatic individuals")

Adults with VTE (see "Overview of the causes of venous thrombosis", section on 'Inherited thrombophilia')

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Sep 2017. | This topic last updated: Sep 28, 2016.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. 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.
  2. Lijfering WM, Brouwer JL, Veeger NJ, et al. Selective testing for thrombophilia in patients with first venous thrombosis: results from a retrospective family cohort study on absolute thrombotic risk for currently known thrombophilic defects in 2479 relatives. Blood 2009; 113:5314.
  3. Haemostasis and Thrombosis Task Force, British Committee for Standards in Haematology. Investigation and management of heritable thrombophilia. Br J Haematol 2001; 114:512.
  4. Andrew M, Paes B, Milner R, et al. Development of the human coagulation system in the full-term infant. Blood 1987; 70:165.
  5. Raffini L. Thrombophilia in children: who to test, how, when, and why? Hematology Am Soc Hematol Educ Program 2008; :228.
  6. 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.
  7. Klaassen IL, van Ommen CH, Middeldorp S. Manifestations and clinical impact of pediatric inherited thrombophilia. Blood 2015; 125:1073.
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. 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.
  13. 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.
  14. 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.
  15. Kearon C, Akl EA, Comerota AJ, et al. Antithrombotic therapy for VTE disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141:e419S.
  16. Foy P, Moll S. Thrombophilia: 2009 update. Curr Treat Options Cardiovasc Med 2009; 11:114.
  17. Kahn SR, Panju A, Geerts W, et al. Multicenter evaluation of the use of venous thromboembolism prophylaxis in acutely ill medical patients in Canada. Thromb Res 2007; 119:145.
  18. Kenet G, Chan A, Goldenberg N. Venous thromboembolism in children: Considerations for thrombophilia testing [update 2013] - Guidance from the perinatal and pediatric Scientific and Standardization Committee of the International Society for Thrombosis and Haemostasis. J Thromb Haemost 2013.
  19. Rosendaal FR, Helmerhorst FM, Vandenbroucke JP. Oral contraceptives, hormone replacement therapy and thrombosis. Thromb Haemost 2001; 86:112.
  20. Vandenbroucke JP, Koster T, Briët E, et al. Increased risk of venous thrombosis in oral-contraceptive users who are carriers of factor V Leiden mutation. Lancet 1994; 344:1453.
  21. Martinelli I, Taioli E, Bucciarelli P, et al. Interaction between the G20210A mutation of the prothrombin gene and oral contraceptive use in deep vein thrombosis. Arterioscler Thromb Vasc Biol 1999; 19:700.
  22. Tormene D, Simioni P, Prandoni P, et al. The incidence of venous thromboembolism in thrombophilic children: a prospective cohort study. Blood 2002; 100:2403.
  23. Grody WW, Griffin JH, Taylor AK, et al. American College of Medical Genetics consensus statement on factor V Leiden mutation testing. Genet Med 2001; 3:139.
  24. Committee on Bioethics. Ethical issues with genetic testing in pediatrics. Pediatrics 2001; 107:1451.
  25. Wertz DC. Ethical, social and legal issues in pharmacogenomics. Pharmacogenomics J 2003; 3:194.
  26. Middeldorp S. Is thrombophilia testing useful? Hematology Am Soc Hematol Educ Program 2011; 2011:150.
  27. Thornburg CD, Dixon N, Paulyson-Nuñez K, Ortel T. Thrombophilia screening in asymptomatic children. Thromb Res 2008; 121:597.
  28. Kenet G, Lütkhoff LK, Albisetti M, et al. Impact of thrombophilia on risk of arterial ischemic stroke or cerebral sinovenous thrombosis in neonates and children: a systematic review and meta-analysis of observational studies. Circulation 2010; 121:1838.