PDF herunterladen
Semin Thromb Hemost 2011; 37(7): 794-801
DOI: 10.1055/s-0031-1297170
© Thieme Medical Publishers

Thrombophilia in Childhood: To Test or Not to Test

C. Heleen van Ommen1 , Saskia Middeldorp2
  • 1Department of Paediatric Haematology, Emma Children's Hospital/Academic Medical Center, Amsterdam, The Netherlands
  • 2Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands
Weitere Informationen

Publikationsverlauf

Publikationsdatum:
20. Dezember 2011 (online)

   Lizenzen und Reprints
Preview

ABSTRACT

Inherited thrombophilia is defined as a genetically determined tendency to develop venous thromboembolism. In children, inherited thrombophilia contributes to the development of pediatric thromboembolic disease. As a consequence, pediatric hematologists are increasingly requested to test thrombophilia in pediatric patients with thrombosis or asymptomatic children from thrombophilic families. This article reviews the benefits and limitations of testing for thrombophilic disorders, for example, factor V Leiden, prothrombin mutation, and deficiencies of antithrombin, protein C, or protein S in childhood.

KEYWORDS

Thrombophilia - venous thromboembolism - pediatrics

REFERENCES

  • 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 (5) 1251-1257
    Suche in Google Scholar
  • 2 van Ommen C H, Heijboer H, Büller H R, Hirasing R A, Heijmans H S, Peters M. Venous thromboembolism in childhood: a prospective two-year registry in The Netherlands.  J Pediatr. 2001;  139 (5) 676-681
    Suche in Google Scholar
  • 3 Raffini L, Huang Y S, 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
    Suche in Google Scholar
  • 4 Manco-Johnson M J. Etiopathogenesis of pediatric thrombosis.  Hematology. 2005;  10 (Suppl 1) 167-170
    Suche in Google Scholar
  • 5 Virchow R. Phlogose and thrombose im Gefässsystem. In: Virchow R, ed. Gesammelte Abhandlungen zur Wissenschaftlichen Medizin. Frankfurt: Von Meidinger Sohn; 1856: 458-636
    Suche in Google Scholar
  • 6 Nowak-Göttl U, von Kries R, Göbel U. Neonatal symptomatic thromboembolism in Germany: two year survey.  Arch Dis Child Fetal Neonatal Ed. 1997;  76 (3) F163-F167
    Suche in Google Scholar
  • 7 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
    Suche in Google Scholar
  • 8 Egeberg O. Inherited antithrombin deficiency causing thrombophilia.  Thromb Diath Haemorrh. 1965;  13 516-530
    Suche in Google Scholar
  • 9 Tait R C, Walker I D, Perry D J et al.. Prevalence of antithrombin deficiency in the healthy population.  Br J Haematol. 1994;  87 (1) 106-112
    Suche in Google Scholar
  • 10 Griffin J H, Evatt B, Zimmerman T S, Kleiss A J, Wideman C. Deficiency of protein C in congenital thrombotic disease.  J Clin Invest. 1981;  68 (5) 1370-1373
    Suche in Google Scholar
  • 11 Tait R C, Walker I D, Reitsma P H et al.. Prevalence of protein C deficiency in the healthy population.  Thromb Haemost. 1995;  73 (1) 87-93
    Suche in Google Scholar
  • 12 Kroiss S, Albisetti M. Use of human protein C concentrates in the treatment of patients with severe congenital protein C deficiency.  Biologics. 2010;  4 51-60
    Suche in Google Scholar
  • 13 Comp P C, Nixon R R, Cooper M R, Esmon C T. Familial protein S deficiency is associated with recurrent thrombosis.  J Clin Invest. 1984;  74 (6) 2082-2088
    Suche in Google Scholar
  • 14 Mahasandana C, Suvatte V, Chuansumrit A et al.. Homozygous protein S deficiency in an infant with purpura fulminans.  J Pediatr. 1990;  117 (5) 750-753
    Suche in Google Scholar
  • 15 Dahlbäck B, Carlsson M, Svensson P J. Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: prediction of a cofactor to activated protein C.  Proc Natl Acad Sci U S A. 1993;  90 (3) 1004-1008
    Suche in Google Scholar
  • 16 Bertina R M, Koeleman BPC, Koster T et al.. Mutation in blood coagulation factor V associated with resistance to activated protein C.  Nature. 1994;  369 (6475) 64-67
    Suche in Google Scholar
  • 17 Rees D C, Cox M, Clegg J B. World distribution of factor V Leiden.  Lancet. 1995;  346 (8983) 1133-1134
    Suche in Google Scholar
  • 18 Poort S R, Rosendaal F R, Reitsma P H, Bertina R M. A common genetic variation in the 3′-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis.  Blood. 1996;  88 (10) 3698-3703
    Suche in Google Scholar
  • 19 Rosendaal F R, Doggen C J, Zivelin A et al.. Geographic distribution of the 20210 G to A prothrombin variant.  Thromb Haemost. 1998;  79 (4) 706-708
    Suche in Google Scholar
  • 20 Tripodi A, Chantarangkul V, Menegatti M, Tagliabue L, Peyvandi F. Performance of clinical laboratories for DNA analyses to detect thrombophilia mutations.  Clin Chem. 2005;  51 (7) 1310-1311
    Suche in Google Scholar
  • 21 Favaloro E J, McDonald D, Lippi G. Laboratory investigation of thrombophilia: the good, the bad, and the ugly.  Semin Thromb Hemost. 2009;  35 (7) 695-710
    Suche in Google Scholar
  • 22 Monagle P, Barnes C, Ignjatovic V et al.. Developmental haemostasis. Impact for clinical haemostasis laboratories.  Thromb Haemost. 2006;  95 (2) 362-372
    Suche in Google Scholar
  • 23 van Teunenbroek A, Peters M, Sturk A, Borm J J, Breederveld C. Protein C activity and antigen levels in childhood.  Eur J Pediatr. 1990;  149 (11) 774-778
    Suche in Google Scholar
  • 24 Kenet G, Lütkhoff L K, 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 (16) 1838-1847
    Suche in Google Scholar
  • 25 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 (5) 915-921
    Suche in Google Scholar
  • 26 van Ommen C H, Heijboer H, van den Dool E J, Hutten B A, 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
    Suche in Google Scholar
  • 27 Bezemer I D, van der Meer F J, Eikenboom J C, Rosendaal F R, Doggen C J. The value of family history as a risk indicator for venous thrombosis.  Arch Intern Med. 2009;  169 (6) 610-615
    Suche in Google Scholar
  • 28 van Sluis G L, Söhne M, El Kheir D Y, Tanck M W, Gerdes V E, Büller H R. Family history and inherited thrombophilia.  J Thromb Haemost. 2006;  4 (10) 2182-2187
    Suche in Google Scholar
  • 29 Massicotte M P, Dix D, Monagle P, Adams M, Andrew M. Central venous catheter related thrombosis in children: analysis of the Canadian Registry of Venous Thromboembolic Complications.  J Pediatr. 1998;  133 (6) 770-776
    Suche in Google Scholar
  • 30 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 (6) 763-766
    Suche in Google Scholar
  • 31 Lijfering W M, Brouwer J L, Veeger N J 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 (21) 5314-5322
    Suche in Google Scholar
  • 32 Baglin T, Luddington R, Brown K, Baglin C. Incidence of recurrent venous thromboembolism in relation to clinical and thrombophilic risk factors: prospective cohort study.  Lancet. 2003;  362 (9383) 523-526
    Suche in Google Scholar
  • 33 Christiansen S C, Cannegieter S C, Koster T, Vandenbroucke J P, Rosendaal F R. Thrombophilia, clinical factors, and recurrent venous thrombotic events.  JAMA. 2005;  293 (19) 2352-2361
    Suche in Google Scholar
  • 34 Bates S M, Greer I A, Pabinger I, Sofaer S, Hirsh J. American College of Chest Physicians . Venous thromboembolism, thrombophilia, antithrombotic therapy, and pregnancy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).  Chest. 2008;  133 (6, Suppl) 844S-886S
    Suche in Google Scholar
  • 35 Baglin T, Gray E, Greaves M British Committee for Standards in Haematology et al. Clinical guidelines for testing for heritable thrombophilia.  Br J Haematol. 2010;  149 (2) 209-220
    Suche in Google Scholar
  • 36 Tormene D, Simioni P, Prandoni P et al.. The incidence of venous thromboembolism in thrombophilic children: a prospective cohort study.  Blood. 2002;  100 (7) 2403-2405
    Suche in Google Scholar
  • 37 Langlois N J, Wells P S. Risk of venous thromboembolism in relatives of symptomatic probands with thrombophilia: a systematic review.  Thromb Haemost. 2003;  90 (1) 17-26
    Suche in Google Scholar
  • 38 Holzhauer S, Stoll M, Thedieck S et al.. Prevalence of thrombophilia and incidence of symptomatic thromboembolism in first degree relatives of pediatric index cases: a prospective cohort study.  J Thromb Haemost. 2009;  7 OC-TU-062
    Suche in Google Scholar
  • 39 Calhoon M J, Ross C N, Pounder E, Cassidy D, Manco-Johnson M J, Goldenberg N A. High prevalence of thrombophilic traits in children with family history of thromboembolism.  J Pediatr. 2010;  157 (3) 485-489
    Suche in Google Scholar
  • 40 Green D. Genetic hypercoagulability: screening should be an informed choice.  Blood. 2001;  98 (1) 20
    Suche in Google Scholar
  • 41 O'Brien S H, Smith K J. Using thrombophilia testing to determine anticoagulation duration in pediatric thrombosis is not cost-effective.  J Pediatr. 2009;  155 (1) 100-104
    Suche in Google Scholar
  • 42 Wade C H, Wilfond B S, McBride C M. Effects of genetic risk information on children's psychosocial wellbeing: a systematic review of the literature.  Genet Med. 2010;  12 (6) 317-326
    Suche in Google Scholar
  • 43 Cohn D M, Vansenne F, Kaptein A A, De Borgie C A, Middeldorp S. The psychological impact of testing for thrombophilia: a systematic review.  J Thromb Haemost. 2008;  6 (7) 1099-1104
    Suche in Google Scholar
  • 44 Coppola A, Tufano A, Cerbone A M, Di Minno G. Inherited thrombophilia: implications for prevention and treatment of venous thromboembolism.  Semin Thromb Hemost. 2009;  35 (7) 683-694
    Suche in Google Scholar
  • 45 Middeldorp S, van Hylckama Vlieg A. Does thrombophilia testing help in the clinical management of patients?.  Br J Haematol. 2008;  143 (3) 321-335
    Suche in Google Scholar

C. Heleen van OmmenM.D. Ph.D. 

Department of Paediatric Haematology, Emma Children's Hospital/Academic Medical Center

Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands

eMail: c.h.vanommen@amc.nl