|
|
Prepublished online as a Blood First Edition Paper on September 12, 2002; DOI 10.1182/blood-2002-03-0944.
Submitted April 5, 2002
Accepted September 2, 2002
Mural thrombus generation in type 2A and 2B von Willebrand disease under flow conditions
Mitsuhiko Sugimoto*, Hideto Matsui, Tomohiro Mizuno, Shizuko Tsuji, Shigeki Miyata, Masanori Matsumoto, Michio Matsuda, Yoshihiro Fujimura, and Akira Yoshioka
Department of Pediatrics, Nara Medical University, Nara, Japan
Division of Transfusion Medicine, National Cardiovascular Center, Osaka, Japan
Department of Blood Transfusion, Nara Medical University, Nara, Japan
Center for Molecular Medicine, Jichi Medical School, Tochigi, Japan
* Corresponding author; email: sugi-ped{at}naramed-u.ac.jp.
To explore the mechanisms that underlie the bleeding tendency in type 2A and 2B von Willebrand disease (VWD), we analyzed the mural thrombus generation process on a collagen surface under physiologic blood flow in a perfusion chamber using whole blood from these VWD patients. At a low shear rate (50 s-1), thrombus generation in all type 2A and 2B VWD patients was comparable to that of normal controls. At a high shear rate (1500 s-1), thrombus generation was impaired in all type 2A patients, whereas that in type 2B VWD patients varied from normal to significantly defective, as judged by epifluorescence microscopy of thrombus surface coverage. However in type 2B patients who showed normal thrombus generation at 1500 s-1, the height and volume of thrombi was significantly reduced, albeit with the normal surface coverage, as compared to control thrombi, and von Willebrand factor (VWF) was poorly distributed within the type 2B thrombus mass when analyzed in detail by confocal laser scanning microscopy. Addition of purified VWF to patient blood completely reversed the defective spatial thrombus growth in type 2B VWD. Thus, our results confirm the impaired thrombus generation in type 2B VWD, which has never been demonstrable in previous in vitro soluble-phase platelet aggregation assays, and point to the critical function of larger VWF multimers in the proper spatial growth of mural thrombi under high shear rate conditions.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
Y. Shida, K. Nishio, M. Sugimoto, T. Mizuno, M. Hamada, S. Kato, M. Matsumoto, K. Okuchi, Y. Fujimura, and A. Yoshioka
Functional imaging of shear-dependent activity of ADAMTS13 in regulating mural thrombus growth under whole blood flow conditions
Blood,
February 1, 2008;
111(3):
1295 - 1298.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Banno, K. Kokame, T. Okuda, S. Honda, S. Miyata, H. Kato, Y. Tomiyama, and T. Miyata
Complete deficiency in ADAMTS13 is prothrombotic, but it alone is not sufficient to cause thrombotic thrombocytopenic purpura
Blood,
April 15, 2006;
107(8):
3161 - 3166.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Vincentelli, S. Susen, T. Le Tourneau, I. Six, O. Fabre, F. Juthier, A. Bauters, C. Decoene, J. Goudemand, A. Prat, et al.
Acquired von Willebrand Syndrome in Aortic Stenosis
N. Engl. J. Med.,
July 24, 2003;
349(4):
343 - 349.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Mekrache, C. Bachelot-Loza, N. Ajzenberg, A. Saci, P. Legendre, and D. Baruch
Activation of pp125FAK by type 2B recombinant von Willebrand factor binding to platelet GPIb at a high shear rate occurs independently of {alpha}IIb{beta}3 engagement
Blood,
June 1, 2003;
101(11):
4363 - 4371.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
