Human platelet activation by thrombolytic agents: Effects of tissue-type plasminogen activator and urokinase on platelet surface P-selectin expression

• Published in: The American heart journal 1998-02, Vol.135 (2), p.268-271
• Main Authors: Kawano, Koichi, Aoki, Isao, Aoki, Nobuo, Homori, Masashi, Maki, Akira, Hioki, Yoshiko, Hasumura, Yukihisa, Terano, Akiyo, Arai, Tomoko, Mizuno, Haruyoshi, Ishikawa, Kyozo
• Format: Article
• Language: English
• Subjects: Aspirin - administration & dosage; Aspirin - pharmacology; Biological and medical sciences; Blood Platelets - drug effects; Blood Platelets - metabolism; Blood. Blood coagulation. Reticuloendothelial system; Flow Cytometry; Humans; Medical sciences; P-Selectin - biosynthesis; P-Selectin - blood; Pharmacology. Drug treatments; Plasminogen Activators - pharmacology; Platelet Activation - drug effects; Tissue Plasminogen Activator - pharmacology; Urokinase-Type Plasminogen Activator - pharmacology
• ISSN: 0002-8703; 1097-6744
• DOI: 10.1016/S0002-8703(98)70092-4

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. (Am Heart J 1998;135:268-71.)