Blood Res.  2016 Sep;51(3):164-170. 10.5045/br.2016.51.3.164.

Venous thromboembolism in pediatric patients: a single institution experience in Korea

• Choi HS
• Choi CW
• Kim HM
• Park HW

• KMID: 2353496
• DOI: http://doi.org/10.5045/br.2016.51.3.164

Abstract

BACKGROUND
While venous thromboembolism (VTE) is uncommon, its incidence is increasing in children. We aimed to evaluate the incidence, risk factors, treatment, and outcome of pediatric VTE cases at a single tertiary hospital in Korea.
METHODS
We retrospectively analyzed the records of consecutive pediatric VTE patients admitted to the Seoul National University Bundang Hospital between April 2003 and March 2016.
RESULTS
Among 70,462 hospitalizations, 25 pediatric VTE cases were identified (3.27 cases per 10,000 admissions). Fifteen patients (60%) were male, 8 were neonates (32%), and the median age at diagnosis was 10.9 years (range, 0 days"’17 yr). Doppler ultrasonography was the most frequently used imaging modality. Thrombosis occurred in the intracerebral (20%), upper venous (64%), lower venous (12%), and combined upper and lower venous systems (4%). Twenty patients (80%) had underlying clinical conditions including venous catheterization (24%), malignancy (20%), and systemic diseases (12%). Protein C, protein S, and antithrombin deficiencies occurred in 2 of 13, 4 of 13, and 1 of 14 patients tested, respectively. Six patients were treated with heparin followed by warfarin, while 4 were treated with heparin or warfarin. Thrombectomy and inferior vena cava filter and/or thrombolysis were performed in 5 patients. Two patients died of pulmonary embolism, and 2 developed a post-thrombotic syndrome.
CONCLUSION
Compared with the reports from Western countries, VTE occurrence was lower in the Korean pediatric population under study, although similar clinical characteristics including bimodal age distribution, underlying diseases, treatment pattern, and outcomes were observed.

Keyword

Venous thromboembolism; Epidemiology; Pediatric patients

MeSH Terms

Age Distribution
Catheterization
Catheters
Child
Diagnosis
Epidemiology
Heparin
Hospitalization
Humans
Incidence
Infant, Newborn
Korea*
Male
Protein C
Protein S
Pulmonary Embolism
Retrospective Studies
Risk Factors
Seoul
Tertiary Care Centers
Thrombectomy
Thrombosis
Ultrasonography, Doppler
Vena Cava Filters
Venous Thromboembolism*
Warfarin
Heparin
Protein C
Protein S
Warfarin

Figure

• 

  Fig. 1 Age distribution (bar graph, right axis) for the pediatric patients with venous thromboembolism (N=25), and total number of neonates, infants, children, and adolescents (linear graph, left axis) admitted to the Seoul National University Bundang Hospital between April 2003 and March 2016.

Reference

1. Chalmers E, Ganesen V, Liesner R, et al. Guideline on the investigation, management and prevention of venous thrombosis in children. Br J Haematol. 2011; 154:196–207. PMID: 21595646.

2. Nowak-Göttl U, Janssen V, Manner D, Kenet G. Venous thromboembolism in neonates and children--update 2013. Thromb Res. 2013; 131(Suppl 1):S39–S41. PMID: 23452739.

3. 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; 124:1001–1008. PMID: 19736261.

4. 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; 59:258–264. PMID: 22038730.

5. Andrew M, David M, Adams M, et al. Venous thromboembolic complications (VTE) in children: first analyses of the Canadian Registry of VTE. Blood. 1994; 83:1251–1257. PMID: 8118029.

6. van Ommen CH, Heijboer H, Büller HR, Hirasing RA, Heijmans HS, Peters M. Venous thromboembolism in childhood: a prospective two-year registry in The Netherlands. J Pediatr. 2001; 139:676–681. PMID: 11713446.

7. Schmidt B, Andrew M. Neonatal thrombosis: report of a prospective Canadian and international registry. Pediatrics. 1995; 96:939–943. PMID: 7478839.

8. Athale U, Siciliano S, Thabane L, et al. Epidemiology and clinical risk factors predisposing to thromboembolism in children with cancer. Pediatr Blood Cancer. 2008; 51:792–797. PMID: 18798556.

9. Sandoval JA, Sheehan MP, Stonerock CE, Shafique S, Rescorla FJ, Dalsing MC. Incidence, risk factors, and treatment patterns for deep venous thrombosis in hospitalized children: an increasing population at risk. J Vasc Surg. 2008; 47:837–843. PMID: 18295440.

10. Chopra V, Anand S, Hickner A, et al. Risk of venous thromboembolism associated with peripherally inserted central catheters: a systematic review and meta-analysis. Lancet. 2013; 382:311–325. PMID: 23697825.

11. Andrew M. Developmental hemostasis: relevance to thromboembolic complications in pediatric patients. Thromb Haemost. 1995; 74:415–425. PMID: 8578498.

12. Jang MJ, Bang SM, Oh D. Incidence of venous thromboembolism in Korea: from the Health Insurance Review and Assessment Service database. J Thromb Haemost. 2011; 9:85–91. PMID: 20942850.

13. Naess IA, Christiansen SC, Romundstad P, Cannegieter SC, Rosendaal FR, Hammerstrøm J. Incidence and mortality of venous thrombosis: a population-based study. J Thromb Haemost. 2007; 5:692–699. PMID: 17367492.

14. Newall F, Wallace T, Crock C, et al. Venous thromboembolic disease: a single-centre case series study. J Paediatr Child Health. 2006; 42:803–807. PMID: 17096717.

15. Wright JM, Watts RG. Venous thromboembolism in pediatric patients: epidemiologic data from a pediatric tertiary care center in Alabama. J Pediatr Hematol Oncol. 2011; 33:261–264. PMID: 21516021.

16. 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–F167. PMID: 9175945.

17. Andrew M, Paes B, Milner R, et al. Development of the human coagulation system in the healthy premature infant. Blood. 1988; 72:1651–1657. PMID: 3179444.

18. White RH. The epidemiology of venous thromboembolism. Circulation. 2003; 107(23 Suppl 1):I4–I8. PMID: 12814979.

19. van Ommen CH, Heijboer H, van den Dool EJ, Hutten BA, Peters M. Pediatric venous thromboembolic disease in one single center: congenital prothrombotic disorders and the clinical outcome. J Thromb Haemost. 2003; 1:2516–2522. PMID: 14675086.

20. Spentzouris G, Scriven RJ, Lee TK, Labropoulos N. Pediatric venous thromboembolism in relation to adults. J Vasc Surg. 2012; 55:1785–1793. PMID: 21944920.

21. Simioni P, Sanson BJ, Prandoni P, et al. Incidence of venous thromboembolism in families with inherited thrombophilia. Thromb Haemost. 1999; 81:198–202. PMID: 10063991.

22. 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; 118:1373–1382. PMID: 18779442.

23. Tuckuviene R, Christensen AL, Helgestad J, Johnsen SP, Kristensen SR. Pediatric venous and arterial noncerebral thromboembolism in Denmark: a nationwide population-based study. J Pediatr. 2011; 159:663–669. PMID: 21596390.

24. Song KS, Park YS, Kim HK, Choi JR, Park Q. Prevalence of Arg306 mutation of the factor V gene in Korean patients with thrombosis. Haemostasis. 1998; 28:276. PMID: 10420078.

25. Ro A, Hara M, Takada A. The factor V Leiden mutation and the prothrombin G20210A mutation was not found in Japanese patients with pulmonary thromboembolism. Thromb Haemost. 1999; 82:1769.

26. Shen MC, Lin JS, Tsay W. Factor V Arg306 --> Gly mutation is not associated with activated protein C resistance and is rare in Taiwanese Chinese. Thromb Haemost. 2001; 85:270–273. PMID: 11246546.

27. 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(2 Suppl):e737S–e801S. PMID: 22315277.

28. Goldenberg NA, Takemoto CM, Yee DL, Kittelson JM, Massicotte MP. Improving evidence on anticoagulant therapies for venous thromboembolism in children: key challenges and opportunities. Blood. 2015; 126:2541–2547. PMID: 26500341.

29. Kahn SR. How I treat postthrombotic syndrome. Blood. 2009; 114:4624–4631. PMID: 19741190.

30. Kumar R, Rodriguez V, Matsumoto JM, et al. Prevalence and risk factors for post thrombotic syndrome after deep vein thrombosis in children: a cohort study. Thromb Res. 2015; 135:347–351. PMID: 25528070.