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.
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.
Taylor
F B
FB
Oklahoma Medical Research Foundation, Oklahoma City 73104, USA.
Coller
B S
BS
Chang
A C
AC
Peer
G
G
Jordan
R
R
Engellener
W
W
Esmon
C T
CT
D000743:Anemia, Hemolytic / Q000097:blood / Q000382:microbiology / Q000517:prevention & control*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D003169:Complement Inactivator Proteins; D004926:Escherichia coli; D004927:Escherichia coli Infections / Q000097:blood*; D006023:Glycoproteins; D010215:Papio; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000276:immunology*; D011951:Receptors, Complement; D012079:Renal Circulation / Q000187:drug effects; D051437:Renal Insufficiency / Q000097:blood / Q000382:microbiology / Q000517:prevention & control*; D013927:Thrombosis / Q000517:prevention & control
D000911:Antibodies, Monoclonal; D003169:Complement Inactivator Proteins; D006023:Glycoproteins; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011951:Receptors, Complement