Clinical and Experimental Pediatrics

The Korean Pediatric Society (대한소아청소년과학회)
권호 표지
DOI QR코드

DOI QR Code

Change of hemostatic markers according to the clinical state in Kawasaki disease

가와사끼병의 임상경과에 따른 지혈성 표지의 변화와 임상적 의의

  • Kim, Yong Beom (Department of Pediatrics, College of Medicine, Chungnam National University) ;
  • Yoon, You Sook (Department of Pediatrics, College of Medicine, Chungnam National University) ;
  • Lee, Sang Yun (Department of Pediatrics, College of Medicine, Chungnam National University) ;
  • Kil, Hong Ryang (Department of Pediatrics, College of Medicine, Chungnam National University)
  • 김용범 (충남대학교 의과대학 소아과학교실) ;
  • 윤유숙 (충남대학교 의과대학 소아과학교실) ;
  • 이상윤 (충남대학교 의과대학 소아과학교실) ;
  • 길홍량 (충남대학교 의과대학 소아과학교실)
  • Received : 2007.09.15
  • Accepted : 2007.10.10
  • Published : 2007.12.15
Download PDF
⟨ Previous Next ⟩

Abstract

Purpose : Pathologically, Kawasaki disease (KD) is associated with widespread vascular endothelial damage in the acute phase. The vasculitis induced endothelial injury leads to coagulation abnormalities. Abnormalities of endothelial function, platelet activation, and fibrinolysis are present during acute phase and long after the onset of KD. The aim of study is to evaluate the change of hemostatic markers in the clinical stages of KD and to assess the hemostatic markers to be a useful indicator of the development of coronary artery lesion (CAL). Methods : Seventy four KD patients diagnosed in Chungnam National University Hospital from November 2004 to June 2007. Eleven febrile control and eleven healthy children were selected for healthy control. All blood samples were collected before and after Intravenous gammaglobulin (IVGG), $2^{nd}$ week, and $4^{th}-8^{th}$ week of illness of KD. Results : Initial D-dimer level of Kawasaki disease showed meaningful difference compared to control group (P<0.05). D-dimer and fibrinogen degradation products (FDP) before IVGG increased compared with normal control group and decreased after IVGG administration. It is normalized until 2 weeks later, and continue to decreasing. D-dimer and FDP were significantly different according to the CAL before IVGG. Conclusion : The hemostatic markers may change to the clinical stage of KD, which may suggest the degree of endothelial injury. Increased some hemostatic markers may be the predictors for development of CAL.

목 적 : 가와사끼병에서 관상동맥의 병변은 잘 알려진 합병증이며 이는 혈소판의 응고성 증가와 혈관 내피세포의 손상이 연관된 것으로 알려져 있다. 그러나 내피세포의 손상과 혈소판 활성화 혹은 응고성 증가와의 관계, 특히 D-dimer나 FDP같은 지혈성 표지(hemostatic marker)의 병기별 변화와 관상동맥병변 발생정도와의 관계 등에 대한 연구는 드물어 본 연구에서 가와사끼병의 임상병기에 따른 지혈성 표지(D-dimer, FDP, antithrombin III)의 변화, 관상동맥병변과의 관련성에 대하여 조사하고자 하였다. 방 법 : 2004년 11월부터 2007년 6월까지 충남대학교병원 소아과에 입원하였던 가와사끼병 환자 74명을 대상군으로 하였고, 대조군 22명은 발열 대조군 11명과 정상대조군 11명으로 나누어 조사하였다. 대상군은 입원 시, IVGG 투여 후, 퇴원 시, 2주, 4- 8주 후에 각각 심장 초음파 및 일반혈액검사, D-dimer, FDP 및 antithrombin III를 포함하는 지혈성 표지에 대한 검사를 시행하였다. 지혈성 표지는 Latex photometric immunoassay를 이용하여 측정하였다. 결 과 : 지혈성 표지에 있어서 D-dimer는 진단 시에 비해 IVGG투여 후 감소하여 2주 후에는 정상으로 회복되었고 이후 지속적으로 감소하였다. 진단 시, IVGG투여 후 모두 유의한 차이가 있었다. 발열 및 정상대조군은 대상군과 유의한 차이가 있었다. FDP는 KD 진단 시와 2주 후 사이에 그리고 발열 및 정상 대조군에 비해 유의한 차이를 보였다. Antithrombin III는 KD 병기에 따라 혹은 대조군 사이에 유의한 차이는 없었다. 관상동맥 병변 유무에 따라 진단 시 D-dimer와 FDP는 유의한 차이를 보였으나, antithrombin III는 유의한 차이가 없었다. 결 론 : 가와사끼병의 임상병기에 따라 지혈성 표지는 변화를 보이며 일부 지혈성 표지는 관상동맥병변 발생의 예측인자로 사용될 수 있다.

Keywords

References

  1. Kawasaki T. Acute febrile mucocutaneous syndrome with lymphoid involvement with specific desquamation of the fingers and toes in children. Arerugi 1967;16:178-222
  2. Suzuki A, Miyagawa-Tomita S, Komatsu K, Nishikawa T, Sakomura Y, Horie T, et al. Active remodeling of the coronary arterial lesions in the late phase Kawasaki disease. Circulation 2000;101:2935-41 https://doi.org/10.1161/01.CIR.101.25.2935
  3. Hergesell O, Andrassy K, Nawroth P. Elevated levels of markers of endothelial cell damage and markers of activated coagulation in patients with systemic necrotizing vasculitis. Thromb Haemost 1996;75:892-8
  4. Burns J, Glode M, Clarke S, Wiggins J Jr, Hathaway WE. Coagulopathy and platelet activation in Kawasaki syndrome: identification of patients at high risk for development of coronary artery aneurysms. J Pediatr 1984;105:206-11 https://doi.org/10.1016/S0022-3476(84)80114-6
  5. Hamamichi Y, Ichida F, Yu X, Hirono KI, Uese KI, Hashimoto I, et al. Neutrophils and mononuclear cells express vascular endothelial growth factor in acute Kawasaki disease: Its possible role in progression of coronary artery lesions. Pediatr Res 2001;49:74-80 https://doi.org/10.1203/00006450-200101000-00017
  6. Ohno T, Igarashi H, Inoue K, Akazawa K, Joh-o K, Hara T. Serum vascular endothelial growth factor: a new predictive indicator for the occurrence of coronary artery lesion in Kawasaki disease. Eur J Pediatr 2000;159:424-9 https://doi.org/10.1007/s004310051300
  7. Miura M, Garcia FL, Crawford SE, Rowley AH. Cell adhesion molecule expression in coronary artery aneurysms in acute kawasaki disease. Pediatr Infect Dis J 2004;23:931-6 https://doi.org/10.1097/01.inf.0000142171.91235.fc
  8. Burgner D, Harnden A. Kawasaki disease: what is the epidemiology telling us about the etiology? Int J Infect Dis 2005;9:185-94 https://doi.org/10.1016/j.ijid.2005.03.002
  9. Dhillon R, Clarkson P, Donald AE, Powe AJ, Nash M, Novelli V, et al. Endothelial dysfunction late after Kawasaki disease. Circulation 1996;94:2103-6 https://doi.org/10.1161/01.CIR.94.9.2103
  10. Suzuki A, Yamagishi M, Kimura K, Sugiyama H, Arakaki Y, Kamiya T, et al. Functional behavior and morphology of the coronary artery wall in patients with Kawasaki disease assessed by intravascular ultrasound. J Am Coll Cardiol 1996;27:291-6
  11. Kato H, Ichinose E, Kawasaki T. Myocardial infarction in kawasaki disease: clinical analysis in 195 cases. J Pediatr 1986;108:923-7 https://doi.org/10.1016/S0022-3476(86)80928-3
  12. Levy DM, Silverman ED, Massicotte MP, McCrindle BW, Yeung RS. Longterm outcomes in patients with giant aneurysms secondary to kawasaki disease. J Rheumatol 2005;32:928-34
  13. Durongpisitkul K, Gururaj VJ, Park JM, Martin CF. The prevention of coronary artery aneurysm in kawasaki disease: a meta-analysis on the efficacy of aspirin and immunoglobulin treatment. Pediatrics 1995;96:1057-61
  14. Williams RV, Tcheng WY, Minich LL. Anticoagulation in the acute and long-term management of kawasaki disease. Progress in Pediatric Cardiology 2004;19:179-88 https://doi.org/10.1016/j.ppedcard.2004.08.012
  15. Furosho K, Kamiya T, Nakano H, Kiyosawa N, Shinomiya K, Hayashidera T, et al. High-dose intravenous gammaglobulin for kawasaki disease. Lancet 1984;324:1055-8 https://doi.org/10.1016/S0140-6736(84)91504-6
  16. Brenderl-Müller K, Hahn A, Schneppenheim R, Santer R. Laboratory signs of activated coagulation are common in Henoch-Schönlein purpura. Pediatr Nephrol 2001;16:1084-8 https://doi.org/10.1007/s004670100033
  17. Imamura T, Yoshihara T, Yokoi K, Nakai N, Ishida H, Kasubuchi Y. Impact of increased D-dimer concentration in Kawasaki disease. Eu J Pediatr 2005;164:526-7 https://doi.org/10.1007/s00431-005-1699-7
  18. Goldenberg NA, Knapp-Clevenger R, Manco-Johnson MJ. Elevated plasma factor VIII and D-dimer levels as predictors of poor outcomes of thrombosis in children. N Engl J Med 2004;351:1081-8 https://doi.org/10.1056/NEJMoa040161
  19. Ten Boekel E, Bartels P. Abnormally short activated partial thromboplastin times are related to elevated plasma levels of TAT, F1＋2, D-dimer and FVIII: Pathophysiol Haemost Thromb 2002;32:137-42 https://doi.org/10.1159/000065217
  20. Lin MT, Tsao LY, Cheng ML, Chang YJ, Chiu HY, Chen HN, et al. Absence of hypercoagulability in acute kawasaki disease. Pediatr Int 2005;47:126-31 https://doi.org/10.1111/j.1442-200x.2005.02025.x