Clinical and Experimental Pediatrics

The Korean Pediatric Society (대한소아청소년과학회)
권호 표지
DOI QR코드

DOI QR Code

Thrombotic thrombocytopenic purpura with decreased level of ADAMTS-13 activity and increased level of ADAMTS-13 inhibitor in an adolescent

청소년기에 발생한 ADAMTS-13 활성도 저하와 항체 양성을 보인 혈전저혈소판혈증자색반병 1례

  • Yang, Eun Mi (Department of Pediatrics, Chonnam National University Hwasun Hospital Chonnam National University Medical School) ;
  • Han, Dong Kyun (Department of Pediatrics, Chonnam National University Hwasun Hospital Chonnam National University Medical School) ;
  • Baek, Hee Jo (Department of Pediatrics, Chonnam National University Hwasun Hospital Chonnam National University Medical School) ;
  • Shin, Myung Geun (Department of Laboratory Medicine, Chonnam National University Hwasun Hospital Chonnam National University Medical School) ;
  • Kim, Young Ok (Department of Pediatrics, Chonnam National University Hwasun Hospital Chonnam National University Medical School) ;
  • Kook, Hoon (Department of Pediatrics, Chonnam National University Hwasun Hospital Chonnam National University Medical School) ;
  • Hwang, Tae Ju (Department of Pediatrics, Chonnam National University Hwasun Hospital Chonnam National University Medical School)
  • 양은미 (전남대학교 의과대학, 화순 전남대학교병원 소아과학교실) ;
  • 한동균 (전남대학교 의과대학, 화순 전남대학교병원 소아과학교실) ;
  • 백희조 (전남대학교 의과대학, 화순 전남대학교병원 소아과학교실) ;
  • 신명근 (전남대학교 의과대학, 화순 전남대학교병원 진단검사의학과교실) ;
  • 김영옥 (전남대학교 의과대학, 화순 전남대학교병원 소아과학교실) ;
  • 국훈 (전남대학교 의과대학, 화순 전남대학교병원 소아과학교실) ;
  • 황태주 (전남대학교 의과대학, 화순 전남대학교병원 소아과학교실)
  • Received : 2009.11.12
  • Accepted : 2010.02.18
  • Published : 2010.03.15
Download PDF
⟨ Previous Next ⟩

Abstract

Thrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy characterized by endothelial cell damage, resulting in microangiopathic hemolytic anemia, thrombocytopenia, and various degrees of neurological and renal impairment caused by microvascular thrombi. It is rare in children and frequently follows a fatal course. TTP is divided into 2 types: one is inherited and associated with ADAMTS-13 gene mutations and the other is acquired and associated with anti-ADAMTS-13 autoantibodies. The measurement of ADAMTS-13 activity in plasma, identification of ADAMTS-13 circulating inhibitor, anti-ADAMTS-13 IgG, and ADAMTS-13 gene sequencing are crucial to the diagnosis of TTP. Plasma exchanges are the first-line treatment for acquired TTP, combined with steroids and immunosuppressive drugs. Here, we describe the case of an adolescent patient with TTP, confirmed by decreased level of ADAMTS-13 activity and an increased level of ADAMTS-13 inhibitor, who was successfully treated by plasma exchanges.

혈전저혈소판혈증자색반병은 혈관 내피 세포 손상에 의한 혈전미세혈관병증으로 미세혈관병용혈빈혈, 혈소판감소증과 미세혈관 혈전에 의한 다양한 정도의 신경 및 신장 침범을 보인다. 이는 소아에서는 드물게 발생하며 종종 치명적인 경과를 보일 수 있다. 혈전저혈소판혈증자색반병은 ADAMTS-13 유전자 변이에 의한 결핍을 보인 선천성 그리고 ADAMTS-13 항체들에 의해 발생하는 후천성인 경우로 분류할 수 있다. ADAMTS-13 활성도 및 순환 항체검사, 그리고 항 ADAMTS-13 IgG와 ADAMTS-13 염기서열분석은 이 질환의 진단에 중요하다. 후천성 환자에게는 혈장교환술이 주된 치료이며, 스테로이드제나 면역억제제도 사용된다. 저자들은 청소년기에 발생한 ADAMTS-13 활성도 저하와 항체 양성을 보인 후천성 혈전저혈소판혈증자색반병을 진단 후 혈장교환술로 효과적으로 치료하였던 1례를 보고하는 바이다.

Keywords

References

  1. Ridolfi RL, Bell WR. Thrombotic thrombocytopenic purpura: report of 25 cases and review of the literature. Medicine 1981;60:413-28 https://doi.org/10.1097/00005792-198111000-00003
  2. Moake JL. Thrombotic microangiopathies. N Engl J Med 2002;347:589-600 https://doi.org/10.1056/NEJMra020528
  3. Ruggenenti P, Noris M, Remuzzi G. Thrombotic microangiopathy, hemolytic uremic syndrome, and thrombotic thrombocytopenic purpura. Kidney Int 2001;60:831–46 https://doi.org/10.1046/j.1523-1755.2001.060003831.x
  4. Moake JL, McPherson PD. Abnormalities of von Willebrand factor multimers in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome. Am J Med 1989:87:9-15 https://doi.org/10.1016/0002-9343(89)90011-9
  5. Furlan M, Robles R, Galbusera M, Remuzzi G, Kyrle PA, Brenner B, et al. Von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura and the hemolyticuremic hemolyticuremic syndrome. N Engl J Med 1998;339:1578–84 https://doi.org/10.1056/NEJM199811263392202
  6. Kremer Hovinga JA, Studt JD, Lammle B. The von Willebrand factor cleaving protease (ADAMTS-13) and the diagnosis of thrombotic thrombocytopenic purpura (TTP). Pathophysiol Haemost Thromb Sep 2003–Dec 2004;33:417–21
  7. Bell WR, Braine HG, Ness PM, Kickler TS. Improved survival in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Clinical experience in 108 patients. N Engl J Med 1991;325:398-403 https://doi.org/10.1056/NEJM199108083250605
  8. Torok TJ, Holman RC, Chorba TL. Increasing mortality from thrombotic thrombocytopenic purpura in the United Statesanalysis of national mortality data, 1968-1991. Am J Hematol 1995;50:84-90 https://doi.org/10.1002/ajh.2830500203
  9. Allford SL, Hunt BJ, Rose P, Machin SJ. Guidelines on the diagnosis and management of the thrombotic microangiopathic haemolytic anaemias. Br J Haematol 2003;120:556–73 https://doi.org/10.1046/j.1365-2141.2003.04049.x
  10. Ashida A, Nakamura H, Yoden A, Tamai H, Ishizashi H, Vagi H, et al. Successful treatment of a young infant who developed high-titer inhibitors against VWF-cleaving protease (ADAMTS-13): important discrimination from Upshaw–Schulman syndrome. Am J Hematol 2002;71: 318–22 https://doi.org/10.1002/ajh.10228
  11. Schneppenheim R, Budde U, Oyen F, Angerhaus D, Aumann V, Drewke E, et al. Von Willebrand factor cleaving protease and ADAMTS13 mutations in childhood TTP. Blood 2003;101:1845–50 https://doi.org/10.1182/blood-2002-08-2399
  12. Horton TM, Stone JD, Yee D, Dreyer Z, Moake JL, Mahoney DH. Case series of thrombotic thrombocytopenic purpura in children and adolescents. J Pediatr Hematol Oncol 2003;25:336–9 https://doi.org/10.1097/00043426-200304000-00016
  13. Moake JL, Turner WA, Stathopoulos NA, Norlasco L, Hellums JD. Involvement of large plasma vWF forms derived from endothelial cells in shear stress induced platelet aggregation. Clin Invest 1986;78:1456-61 https://doi.org/10.1172/JCI112736
  14. Tsai HM. Physiologic cleavage of vWF by a plasma protease dependent on its conformation and requires ion. Blood 1996;87:4235-44
  15. Tsai HM. The molecular biology of thrombotic microangiopathy. Kidney Int 2006;70:16–23 https://doi.org/10.1038/sj.ki.5001535
  16. Sadler JE, Moake JL, Miyata T, George JN. Recent advances in thrombotic thrombocytopenic purpura. Hematology 2004;407–23
  17. George JN. Clinical practice. Thrombotic thrombocytopenic purpura. N Engl J Med 2006;354:1927–35 https://doi.org/10.1056/NEJMcp053024
  18. Mannuci PM, Vanoli M, Forza I, Canciani MT, Scorza R. Von Willebrand factor cleaving protease (ADAMTS-13) in 123 patients with connective tissue disease (systemic lupus erythemaotosus and systemic sclerosis). Haematologica 2003;88:914-8
  19. Lewis EJ, Hunsicker LG, Lan SP, Rohde RD, Lachin JM. A controlled trial of plasmapheresis therapy in severe lupus nephritis. N Engl J Med 1992;326:1373–9 https://doi.org/10.1056/NEJM199205213262101
  20. Hamasaki K, Mimura T, Kanda H, Kubo K, Setoguchi K, Satoh T, et al. Systemic lupus erythemotosus and thrombotic thrombocytopenic purpura: a case report and literature review. Clin Rheumatol 2003;22:355-8 https://doi.org/10.1007/s10067-003-0742-1

Cited by

  1. Von Willebrand Factor-Cleaving Protease Activity in Thrombotic Microangiopathy: First Report From Iran vol.6, pp.6, 2014, https://doi.org/10.5812/numonthly.18900