[Different inhibiting effects of abciximab and tirofiban on platelet thrombus formation on a collagen surface under flow conditions].
OBJECTIVE
Recently developed anti-GPIIb/IIIa agents effectively inhibit acute thrombotic occlusion of coronary arteries after interventional treatment, and have similar inhibiting effects on plasma ligand binding to GPIIb/IIIa. Clinical investigation has revealed that abciximab, the chimeric monoclonal antibody against GPIIb/IIIa, has superior in vivo antithrombotic effects to other agents. The inhibiting effects of abciximab and another anti-GPIIb/IIIa agent, tirofiban, were investigated on platelet thrombus formation on a collagen surface under flow conditions.


METHODS
Blood was drawn from 6 normal volunteers and anticoagulated with a specific inhibitor of thrombin, argatroban, at a final concentration of 100 microM. Platelets were rendered fluorescent by addition of mepacrine to a final concentration of 10 microM. Mepacrine is concentrated in the dense granules of platelets and leukocytes, but does not accumulate in red blood cells, so platelet thrombi can be detected by fluorescence microscopy even in the presence of red blood cells. Horizontal glass slips covered with fibrillar type I collagen were assembled in a Hele-Shaw type flow chamber.


RESULTS
Platelet thrombi were developed on the collagen surface even in the absence of platelet activating agents. Both abciximab and tirofiban inhibited the platelet thrombus formation. Single platelet adhesion on the collagen surface was inhibited only by abciximab and not by tirofiban.


CONCLUSIONS
The superior in vivo antithrombotic effects of abciximab may be partially explained by its inhibiting effects on the platelet adhesion on exposed subendothelial matrix.
Shimazaki
T
T
Division of Cardiology, Tokai University School of Medicine, Kanagawa.
Goto
S
S
Sakakibara
M
M
Eto
K
K
Kim
J Y
JY
Ichikawa
N
N
Yoshida
M
M
Nagaoka
Y
Y
Isshiki
T
T
Handa
S
S
D000077284:Abciximab; D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000925:Anticoagulants / Q000494:pharmacology*; D003094:Collagen; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology*; D066298:In Vitro Techniques; D008856:Microscopy, Fluorescence; D010973:Platelet Adhesiveness / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D013927:Thrombosis / Q000517:prevention & control*; D000077466:Tirofiban; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D000925:Anticoagulants; D005343:Fibrinolytic Agents; D007140:Immunoglobulin Fab Fragments; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D014443:Tyrosine; D003094:Collagen; D000077466:Tirofiban; D000077284:Abciximab