|
|
 Previous Article | Table of Contents | Next Article 
7E3 F(ab')2, a monoclonal antibody to the platelet GPIIb/IIIa receptor,
protects against microangiopathic hemolytic anemia and microvascular
thrombotic renal failure in baboons treated with C4b binding protein and a
sublethal infusion of Escherichia coli
FB Taylor, BS Coller, AC Chang, G Peer, R Jordan, W Engellener and CT Esmon
Oklahoma Medical Research Foundation, Oklahoma City 73104, USA.
We have used our previously described baboon model of infusion of both a
sublethal dose of Escherichia coli and C4b binding protein to assess the
impact of inhibiting platelet function with the F(ab')2 fragment of the
monoclonal antibody 7E3, directed against the platelet glycoprotein
(GP)IIb/IIIa receptor, on the characteristic microvascular changes. At a
dose of 0.25 to 0.35 mg/kg bolus plus an infusion of 0.25 to 0.35 mg/kg
over 6 hours, c7E3 F(ab')2 had only a minimal impact on fibrinogen
consumption and delayed but did not prevent, the development of
thrombocytopenia. Treatment with 7E3 F(ab')2, however, produced significant
protection from the development of microangiopathic hemolysis and renal
insufficiency. Histologic examination supported these observations, with
treated animals having fewer schistocytes on blood smear and less evidence
of ischemic renal changes. Treated animals also had more rapid recovery of
peripheral white blood counts, suggesting a possible protective effect of
treatment on ischemic damage to the bone marrow. These data indicate that
potent inhibition of platelet function via GPIIb/IIIa receptor blockade can
decrease ischemic organ damage in this animal model that has features
similar to those found in diffuse intravascular coagulation, hemolytic
uremic syndrome, and thrombotic thrombocytopenic purpura.
Volume 89,
Issue 11,
pp. 4078-4084,
06/01/1997
Copyright © 1997 by The American Society of Hematology
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
G. Zhang, J. Han, E. J. Welch, R. D. Ye, T. A. Voyno-Yasenetskaya, A. B. Malik, X. Du, and Z. Li
Lipopolysaccharide Stimulates Platelet Secretion and Potentiates Platelet Aggregation via TLR4/MyD88 and the cGMP-Dependent Protein Kinase Pathway
J. Immunol.,
June 15, 2009;
182(12):
7997 - 8004.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Andonegui, S. M. Kerfoot, K. McNagny, K. V. J. Ebbert, K. D. Patel, and P. Kubes
Platelets express functional Toll-like receptor-4
Blood,
October 1, 2005;
106(7):
2417 - 2423.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. C. Aird
The role of the endothelium in severe sepsis and multiple organ dysfunction syndrome
Blood,
May 15, 2003;
101(10):
3765 - 3777.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. S. Smyth, E. D. Reis, H. Vaananen, W. Zhang, and B. S. Coller
Variable protection of {beta}3-integrin-deficient mice from thrombosis initiated by different mechanisms
Blood,
August 15, 2001;
98(4):
1055 - 1062.
[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]
|
|
|
|
|
|
|
T. Bombeli, B. R. Schwartz, and J. M. Harlan
Adhesion of Activated Platelets to Endothelial Cells: Evidence for a GPIIbIIIa-dependent Bridging Mechanism and Novel Roles for Endothelial Intercellular Adhesion Molecule 1 (ICAM-1), {alpha}v{beta}3 Integrin, and GPIb{alpha}
J. Exp. Med.,
February 2, 1998;
187(3):
329 - 339.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
