Human platelet activation by thrombolytic agents: effects of tissue-type plasminogen activator and urokinase on platelet surface P-selectin expression.
The mechanisms that underlie reocclusion during thrombolytic therapy have not yet been clarified. The purpose of this study was to investigate the activating effects of tissue-type plasminogen activator and urokinase and the inhibitory effects of acetylsalicylic acid by measuring platelet surface P-selectin as a marker of platelet activation. After addition of urokinase (final concentration 192 U/ml, 1920 U/ml, or 19,200 U/ml) or tissue-type plasminogen activator (final concentration 120 U/ml, 1200 U/ml, or 12,000 U/ml) to platelet-rich plasma from 12 healthy persons, platelet surface P-selectin expression was measured by means of flow cytometry with an anti-CD62 monoclonal antibody. The presence of urokinase and tissue-type plasminogen activator increased platelet surface P-selectin expression in a concentration-dependent manner. In the next step, either 160 mg/day (n = 6) or 660 mg/day (n = 6) acetylsalicylic acid was administered to the 12 healthy persons, and venous blood samples were collected after 7 days of treatment. Platelet surface P-selectin expression was measured with the method used earlier and after addition of tissue-type plasminogen activator or urokinase. Although the effect of acetylsalicylic acid at 160 mg/day on P-selectin expression was minimal, a dose of 660 mg/day suppressed platelet P-selectin expression and inhibited the platelet activating effects of tissue-type plasminogen activator and urokinase in a statistically significant way. Platelets were activated by tissue-type plasminogen activator or urokinase, and this platelet activation was suppressed with administration of acetylsalicylic acid at 660 mg/day.
Kawano
K
K
Second Department of Internal Medicine, Kyorin University School of Medicine, Mitaka-city, Tokyo, Japan.
Aoki
I
I
Aoki
N
N
Homori
M
M
Maki
A
A
Hioki
Y
Y
Hasumura
Y
Y
Terano
A
A
Arai
T
T
Mizuno
H
H
Ishikawa
K
K
D001241:Aspirin / Q000008:administration & dosage / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D019007:P-Selectin / Q000096:biosynthesis* / Q000097:blood; D010960:Plasminogen Activators / Q000494:pharmacology*; D015539:Platelet Activation / Q000187:drug effects*; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*; D014568:Urokinase-Type Plasminogen Activator / Q000494:pharmacology*
D019007:P-Selectin; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator; D001241:Aspirin