Ability of anti-glycoprotein IIb/IIIa agents to dissolve platelet thrombi formed on a collagen surface under blood flow conditions.
OBJECTIVE
We examined the lytic effects of anti-glycoprotein (GP) IIb/IIIa agents on platelet thrombi formed on the collagen surface under blood flow conditions.


BACKGROUND
Anti-GP IIb/IIIa agents may influence platelet thrombi already formed.


METHODS
Blood samples were anticoagulated either by the specific antithrombin Argatroban (100 microM) or by unfractionated heparin (0.1 U/ml). After platelet thrombi were formed on a collagen surface following 6-min perfusion of whole blood obtained from eight adult donors containing fluorescinated platelets at a wall shear rate of 1,500 s(-1), additional blood samples from the same donors either containing or not containing anti-GP IIb/IIIa agents (abciximab, eptifibatide, or tirofiban) were perfused on these thrombi. The three-dimensional structures of the platelet thrombi were continuously observed by laser confocal microscopy equipped with a piezo-electric motor control unit and recorded.


RESULTS
The platelet thrombi started to dissolve after perfusion of blood containing the anti-GP IIb/IIIa agents, whereas their growth resumed after subsequent perfusion of control blood. Only a single layer of platelets having heights of 3 +/- 1 microm, 3 +/- 2 microm, and 3 +/- 1 microm, respectively, could be seen after 6-min perfusion of blood containing abciximab, eptifibatide, and tirofiban, whereas the initial height of the platelet thrombi of 8 +/- 2 microm increased to 11 +/- 4 microm after subsequent perfusion of control blood (n = 8). The volume of the platelet thrombi, which was 3,352 +/- 1,045 microm(3) before starting the second perfusion, was reduced to 778 +/- 102 microm(3), 812 +/- 122 microm(3), and 856 +/- 144 microm(3) after 6-min perfusion of blood containing abciximab, eptifibatide, and tirofiban, respectively.


CONCLUSIONS
We have shown in this study that anti-GP IIb/IIIa agents possess the ability to dissolve platelet thrombi.
Goto
Shinya
S
Department of Medicine, Tokai University School of Medicine, Kanagawa, Japan. sgoto3@mac.com
Tamura
Noriko
N
Ishida
Hideyuki
H
D000077284:Abciximab; D000328:Adult; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000925:Anticoagulants / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D003094:Collagen; D000077542:Eptifibatide; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D018056:Hemorheology; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology; D066298:In Vitro Techniques; D010455:Peptides / Q000494:pharmacology; D010875:Pipecolic Acids / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors*; D013449:Sulfonamides; D013927:Thrombosis / Q000503:physiopathology* / Q000628:therapy; D000077466:Tirofiban; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D000925:Anticoagulants; D005343:Fibrinolytic Agents; D007140:Immunoglobulin Fab Fragments; D010455:Peptides; D010875:Pipecolic Acids; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D013449:Sulfonamides; D014443:Tyrosine; D003094:Collagen; D001120:Arginine; D000077466:Tirofiban; C031942:argatroban; D000077542:Eptifibatide; D000077284:Abciximab