Highlights
- •In pediatric patients significant associations were noted between thrombosis occurrence and presence of inherited thrombophilic (IT) risk factors.
- •Currently evidence is still lacking as to whether IT influence the clinical outcome in pediatric VTE.
- •IT testing in children should be individualized and discussed with patients and their families.
- •For adolescents with unprovoked VTE and in children with a positive family history for VTE screening IT tests are recommended and should be performed in a specialized coagulation unit.
Abstract
Venous thrombosis (VTE) in children is gaining increased awareness and apart from
underlying medical conditions, recently reported systematic reviews on pediatric VTE
(70% provoked) have shown significant associations between thrombosis and presence
of inherited thrombophilic risk factors (IT), such as protein C-, protein S- and antithrombin
deficiency, mutations of factor 5 (F5: rs6025) and factor 2 (F2: rs1799963), even more pronounced when combined IT were involved. Although we have
learned more about the pathophysiology of VTE with the increased discovery of IT evidence
is still lacking as to whether IT influence the clinical outcome in pediatric VTE.
It still remains controversial as to whether children with VTE or offspring from thrombosis-prone
families benefit from IT screening. Thus, IT testing in children should be individualized.
If the decision “pro screening” is discussed as an appropriate option in adolescents
with unprovoked VTE and in children with a positive family history for VTE screening
should be performed in a specialized coagulation unit for acquired or inherited and
prothrombotic defects based on the individual population background. Apart from the
laboratory assessment for the presence/absence of lupus anticoagulants and antiphospholipid
antibodies screening should be performed beyond the acute VTE onset and after withdrawal
of anticoagulant medication possibly influencing laboratory results.
Keywords
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References
- Venous thromboembolic complications (VTE) in children: first analyses of the Canadian Registry of VTE.Blood. 1994; 83: 1251-1257
- Neonatal thrombosis: report of a prospective Canadian and international registry.Pediatrics. 1995; 96: 939-943
- Role of endogenous testosterone concentration in pediatric stroke.Ann. Neurol. 2009; 66: 754-758
- Neonatal symptomatic thromboembolism in Germany: two year survey.Arch. Dis. Child. Fetal Neonatal Ed. 1997; 76F163-F7
- A cross-sectional study evaluating post-thrombotic syndrome in children.Thromb. Res. 2003; 111: 227-233
- Post-thrombotic syndrome in children: a systematic review of frequency of occurrence, validity of outcome measures, and prognostic factors.Haematologica. 2010; 95: 1952-1959
- Postthrombotic syndrome following upper extremity deep vein thrombosis in children.Blood. 2014; 124: 1166-1173
- Central venous catheter related thrombosis in children: analysis of the Canadian Registry of venous thromboembolic complications.J. Pediatr. 1998; 133: 770
- Venous thromboembolism in childhood: a prospective two-year registry in The Netherlands.J. Pediatr. 2001; 139: 676-681
- Dramatic increase in venous thromboembolism in children's hospitals in the United States from 2001 to 2007.Pediatrics. 2009; 124: 1001-1008
- Pediatric venous thromboembolism in the United States: a tertiary care complication of chronic diseases.Pediatr. Blood Cancer. 2012; 59: 258-264
- Multicentre evaluation of combined prothrombotic defects associated with thrombophilia in childhood. Childhood Thrombophilia Study Group.Eur. J. Pediatr. 1999; 158S97-S04
- Risk factors for venous thromboembolism. Results from the Copenhagen City heart study.Circulation. 2010; 121: 1896-1903
- Prevalence of deep vein thrombosis in acutely admitted ambulatory non-surgical intensive care unit patients.BMC. Res. Notes. 2014; 7: 431
- Risk marker associations with venous thrombotic events: a cross-sectional analysis.BMJ Open. 2014; 4e003208
- Childhood Thrombophilia Study Group. Risk of recurrent venous thrombosis in children with combined prothrombotic risk factors.Blood. 2001; 97: 858-862
- Mountain States Regional Thrombophilia Group. Elevated plasma factor VIII and D-dimer levels as predictors of poor outcomes of thrombosis in children.New Engl. J. Med. 2004; 351: 1081-1088
- Familial elevated factor VIII in children with symptomatic venous thrombosis and post-thrombotic syndrome: results of a multicenter study.Arterioscler. Thromb. Vasc. Biol. 2006; 26: 1901-1906
- Risk factors and co-morbidities in adolescent thromboembolism are different than those in younger children.Thromb. Res. 2016; 141: 178-182
- Venous thromboembolism occurring during adolescence.Arch. Dis. Child. 2016; 101: 427-432
- Impact of inherited thrombophilia on venous thromboembolism in children: a systematic review & meta-analysis of observational studies.Circulation. 2008; 118: 1373-1382
- Impact of inherited thrombophilia on arterial ischemic stroke and cerebral sinovenous thrombosis in children: a systematic review and meta-analysis of observational studies.Circulation. 2010; 121: 1838-1847
- Impact of persistent antiphospholipid antibodies on symptomatic thromboembolism in children: a systematic review & meta-analysis [observational studies].Semin. Thromb. Haemost. 2011; 37: 802-809
- Clinical and laboratory characteristics of pediatric and adolescent index cases with venous thromboembolism and antithrombin deficiency: an observational multicenter cohort study.Thromb. Haemost. 2014; 112: 478-485
- Clinical and laboratory characteristics of children with venous thromboembolism and protein C-deficiency: an observational Israeli-German cohort study.Br. J. Haematol. 2014; 167: 385-393
- Role of protein S deficiency in children with venous thromboembolism: an observational international cohort study.Thromb. Haemost. 2015; 113: 426-433
- Impact of high-risk thrombophilia status on recurrence among children with a first non-central-venous-catheter-associated VTE: an observational multicentre cohort study.Br. J. Haematol. 2016; 175: 133-140
- Impact of high risk thrombophilia status on recurrence among children and adults with VTE: an observational multicenter cohort study.Blood Cells Mol. Dis. 2016; 62: 24-31
- Inherited thrombophilia in children with venous thromboembolism and the familial risk of thromboembolism: an observational study.Blood. 2012; 120: 1510-1515
- The incidence of venous thromboembolism in thrombophilic children: a prospective cohort study.Blood. 2002; 100: 2403-2405
- High prevalence of thrombophilic traits in children with family history of thromboembolism.J. Pediatr. 2010; 157: 485-489
- Risk factors for thromboembolism teens: when should I test?.Curr. Opin. Pediatr. 2002; 14: 370-378
- Diagnostic value of family histories of thrombosis to identify children with thrombophilia.Pediatr. Hematol. Oncol. 2005; 22: 453-462
- Efficacy of familial history in determining thrombophilia risk.J. Pediatr. Adolesc. Gynecol. 2007; 20: 221
- Psychological impact of testing for thrombophilic alterations.Thromb. Haemost. 2006; 96: 348-355
- Psychological impact of thrombophilia testing in asymptomatic family members.Thromb. Res. 2011; 128: 530-535
- Neonatal renal vein thrombosis: review of the English-Language literature between 1992 and 2006.Pediatrics. 2007; 120e1278-84
- Definition of post-thrombotic syndrome following lower extremity deep venous thrombosis and standardization of outcome measurement in pediatric clinical investigations.J. Thromb. Haemost. 2011; 10: 477-480
- Standardization of post-thrombotic syndrome definition and outcome assessment following upper venous system thrombosis in pediatric practise.J. Thromb. Haemost. 2012; 10: 2182-2185
- Health-related quality of life in children and young adults with post-thrombotic syndrome: results from a cross-sectional study.Pediatr. Blood Cancer. 2014; 61: 546-551
- Health-related quality of life in children and adolescents with stroke, self-reports and parent/proxies report: cross-sectional investigation.Ann. Neurol. 2011; 70: 70-78
- Risk factors for symptomatic venous and arterial thromboembolism in newborns, children and adolescents - what did we learn within the last 20years?.Blood Cells Mol. Dis. 2017; 67: 18-22https://doi.org/10.1016/j.bcmd.2016.12.003
- Inherited thrombophilia in pediatric venous thromboembolic disease: why and who to test.Front. Pediatr. 2017 Mar 14; 5 (eCollection 2017): 50https://doi.org/10.3389/fped.2017.00050
- No impact of endogenous prothrombotic conditions on the risk of central venous line-related thrombotic events in children: results of the KIDCAT study (KIDs with Catheter Associated Thrombosis).J. Thromb. Haemost. 2014; 12: 1610-1615
- Genetic factors in pediatric venous thromboembolism.Thromb. Res. 2017 Mar; 151: S97-S99
- Rare genetic variants in SMAP1, B3GAT2, and RIMS1 contribute to pediatric venous thromboembolism.Blood. 2017; 129: 783-790
- Is thrombophilia testing useful?.Hematology Am. Soc. Hematol. Educ. Program. 2011; 2011: 150-155
- Economic evaluations of thrombophilia screening prior to prescribing combined oral contraceptives: a systematic and critical review.Appl. Health Econ. Health Policy. 2017; 15: 583-595
- Clinical guidelines for testing for heritable thrombophilia.Br. J. Haematol. 2010; 149: 209-220
- Oral contraceptives and HRT risk of thrombosis.Clin. Appl. Thromb. Hemost. 2017; https://doi.org/10.1177/1076029616683802
Article info
Publication history
Published online: February 20, 2018
Accepted:
February 15,
2018
Received in revised form:
January 31,
2018
Received:
January 3,
2018
Identification
Copyright
© 2018 Published by Elsevier Ltd.
