Inhibitory effect of activated protein C on platelet aggregation induced by the prothrombin-converting reaction

• Published in: Thrombosis research Vol. 67; no. 6; pp. 705 - 710
• Main Authors: Komoriya, Keiji, Inoue, Kyoko, Takahashi, Katsushi, Suzuki, Koji
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Ltd 15.09.1992; Elsevier Science
• Subjects: activated protein C; Biological and medical sciences; Blood coagulation. Blood cells; Blood Platelets - drug effects; Blood Platelets - metabolism; Coumarins; Factor Xa - metabolism; Factor Xa - pharmacology; Fluorescent Dyes; Fundamental and applied biological sciences. Psychology; Humans; In Vitro Techniques; Molecular and cellular biology; Oligopeptides; Platelet; platelet aggregation; Platelet Aggregation - drug effects; Platelet Aggregation - physiology; Platelet Aggregation Inhibitors - pharmacology; Protein C - metabolism; Protein C - pharmacology; Prothrombin - metabolism; Prothrombin - pharmacology; thrombin; Thrombin - biosynthesis; Thrombin - pharmacology; thrombin; activated protein C; platelet aggregation; Aggregation; Human; Protein C; Platelet; Inhibition
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/0049-3848(92)90074-K

The present study was undertaken to elucidate the effect on platelet aggregation of the prothrombin-converting reaction on platelets with or without activated protein C (APC). A reaction mixture of washed platelets from human individuals, Factor Xa and prothrombin markedly induced platelet aggregation; maximum aggregation rates, 31.3–92.5%, and times to reach to maximum aggregation, 11.6 to 20.1 min. This aggregation was inhibited by the addition of APC with 50% inhibition concentration (IC 50) value of 14.4 U/ml. APC also inhibited thrombin generation in the reaction mixture in a dose-dependent manner with IC50 value of 0.96 U/ml. However, APC did not inhibit the thrombin (0.1 CU/ml)-induced platelet aggregation at concentrations of up to 30 U/ml. These findings suggest that APC has no direct inhibitory effect on platelet aggregation and that APC inhibits platelet aggregation through inhibition of thrombin generation.