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Sera from patients with heparin-induced thrombocytopenia generate
platelet-derived microparticles with procoagulant activity: an explanation
for the thrombotic complications of heparin-induced thrombocytopenia
TE Warkentin, CP Hayward, LK Boshkov, AV Santos, JA Sheppard, AP Bode and JG Kelton
Department of Laboratory Medicine, Hamilton Civic Hospitals (General
Division), Ontario, Canada.
Heparin-induced thrombocytopenia is characterized by moderate
thrombocytopenia and thrombotic complications, whereas
quinine/quinidine-induced thrombocytopenia usually presents with severe
thrombocytopenia and bleeding. Using flow cytometry and assays of
procoagulant activity, we investigated whether sera from patients with
these immune drug reactions could stimulate normal platelets to generate
platelet-derived microparticles with procoagulant activity. Sera or
purified IgG from patients with heparin-induced thrombocytopenia stimulated
the formation of platelet-derived microparticles in a heparin-dependent
fashion. Further studies showed that heparin-induced thrombocytopenia sera
also produced a marked increase in procoagulant activity. In contrast, sera
from patients with quinine- or quinidine-induced thrombocytopenia did not
generate platelet-derived microparticles nor generate increased
procoagulant activity. However, quinine/quinidine-induced thrombocytopenia
sera produced a significant increase in the binding of IgG to platelets in
a drug-dependent fashion, whereas sera from patients with heparin-induced
thrombocytopenia demonstrated no drug-dependent binding of IgG to
platelets. We also observed increased levels of circulating microparticles
in patients with acute heparin-induced thrombocytopenia compared with
control patients. Our observations indicate that the generation of
procoagulant platelet-derived microparticles in vivo is a plausible
explanation for the thrombotic complications observed in some patients with
heparin-induced thrombocytopenia.
Volume 84,
Issue 11,
pp. 3691-3699,
12/01/1994
Copyright © 1994 by The American Society of Hematology
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|
|
|
|
|
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|
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|
|
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|
|
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|
|
|
|
|
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|
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|
|
|
|
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|
|
|
|
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[Full Text]
[PDF]
|
|
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|
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K. Moshfegh, M. Redondo, F. Julmy, W. A. Wuillemin, M. U. Gebauer, A. Haeberli, and B. J. Meyer
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36(3):
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[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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96(3):
846 - 851.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. F. Schenk, G. Berg, S. Morsdorf, B. Stefan, H. Kroll, B. Krischek, G. Pindur, H. Schieffer, and E. Wenzel
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6(3):
151 - 156.
[Abstract]
[PDF]
|
|
|
|
|
|
|
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Morphological analysis of microparticle generation in heparin-induced thrombocytopenia
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July 1, 2000;
96(1):
188 - 194.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Nieuwland, R. J. Berckmans, S. McGregor, A. N. Boing, F. P. H. Th. M. Romijn, R. G. J. Westendorp, C. E. Hack, and A. Sturk
Cellular origin and procoagulant properties of microparticles in meningococcal sepsis
Blood,
February 1, 2000;
95(3):
930 - 935.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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Safety of Warfarin Anticoagulation in Patients With Heparin-Induced Thrombocytopenia
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November 1, 1999;
116(5):
1333 - 1338.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. E. Wallis, B. E. Lewis, H. L. Messmore, R. Pifarre, and J. M. Walenga
Inadequacy of Current Prevention Strategies for Heparin-Induced Thrombocytopenia
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October 1, 1999;
5(1_suppl):
S16 - S20.
[Abstract]
[PDF]
|
|
|
|
|
|
|
A. Greinacher, U. Janssens, G. Berg, M. Bock, H. Kwasny, B. Kemkes-Matthes, P. Eichler, H. Volpel, B. Potzsch, and M. Luz
Lepirudin (Recombinant Hirudin) for Parenteral Anticoagulation in Patients With Heparin-Induced Thrombocytopenia
Circulation,
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