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Case Report
A Case of Pediatric Unprovoked Deep Vein Thrombosis due to Combined Hereditary Thrombophilia of Antithrombin III and Protein S Deficiency
Clin Pediatr Hematol Oncol 2018;25:185-90.
Published online October 31, 2018
© 2018 Korean Society of Pediatric Hematology-Oncology and Korean Society for Pediatric Neuro-Oncology

Jeong Yeon Kim, M.D.1, I-Seok Kang, M.D.1 and Hee-Jin Kim, M.D., Ph.D.2

Departments of 1Pediatrics and 2Laboratory Medicine & Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
Correspondence to: I-Seok Kang
Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea
Tel: +82-2-3410-3531
Fax: +82-2-3410-0043
Received September 4, 2018; Revised September 26, 2018; Accepted October 5, 2018.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Unprovoked deep vein thrombosis (DVT) is uncommon in pediatric patients and, among those, combined hereditary thrombophilia is particularly rare. We present a 9-year-old Korean boy who developed lower extremity pain with swelling, and was diagnosed with unprovoked DVT due to hereditary (combined hereditary thrombophilia). Coagulation test revealed antithrombin III and protein S deficiency. The genetic work up confirmed the first case of combined antithrombin III deficiency and protein S deficiency by SERPINC1 heterozygous termination mutation [c.685C>T (p.Arg229*)] and PROS1 heterozygous missense mutation [c.1597G>A (p.Val533Met)]. He was treated with continuous heparin and catheter intervention but those were ineffective or transiently effective. His DVT gradually improved only after prolonged anticoagulation.
Keywords: Deep vein thrombosis, Hereditary thrombophilia, Pediatric, Anticoagulation
  1. van Ommen CH, Nowak-Göttl U. Inherited thrombophilia in pediatric venous thromboembolic disease: why and who to test. Front Pediatr 2017;5:50.
    Pubmed KoreaMed CrossRef
  2. Choi HS, Choi CW, Kim HM, Park HW. Venous thromboembolism in pediatric patients: a single institution experience in Korea. Blood Res 2016;51:164-70.
    Pubmed KoreaMed CrossRef
  3. Jung HL. Venous thromboembolism in children and adolescents. Blood Res 2016;51:149-51.
    Pubmed KoreaMed CrossRef
  4. 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;1:2516-22.
    Pubmed CrossRef
  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;83:1251-7.
  6. 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.
    Pubmed CrossRef
  7. Yang JY, Chan AK. Pediatric thrombophilia. Pediatr Clin North Am 2013;60:1443-62.
    Pubmed CrossRef
  8. Makris M. Thrombophilia: grading the risk. Blood 2009;113:5038-9.
    Pubmed CrossRef
  9. Nakashima MO, Rogers HJ. Hypercoagulable states: an algorithmic approach to laboratory testing and update on monitoring of direct oral anticoagulants. Blood Res 2014;49:85-94.
    Pubmed KoreaMed CrossRef
  10. Kim HJ, Seo JY, Lee KO, et al. Distinct frequencies and mutation spectrums of genetic thrombophilia in Korea in comparison with other Asian countries both in patients with thromboembolism and in the general population. Haematologica 2014;99:561-9.
    Pubmed KoreaMed CrossRef
  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;118:1373-82.
    Pubmed CrossRef
  12. Shen MC, Lin JS, Tsay W. High prevalence of antithrombin III, protein C and protein S deficiency, but no factor V Leiden mutation in venous thrombophilic Chinese patients in Taiwan. Thromb Res 1997;87:377-85.
  13. Su J, Shu L, Zhang Z, et al. A small deletion in SERPINC1 causes type I antithrombin deficiency by promoting endoplasmic reticulum stress. Oncotarget 2016;7:76882-90.
    Pubmed KoreaMed CrossRef
  14. Heeb MJ. Role of the PROS1 gene in thrombosis: lessons and controversies. Expert Rev Hematol 2008;1:9-12.
    Pubmed KoreaMed CrossRef

October 2018, 25 (2)
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  • I-Seok Kang