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

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 aggregati...

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Veröffentlicht in:Thrombosis research 1992-09, Vol.67 (6), p.705-710
Hauptverfasser: Komoriya, Keiji, Inoue, Kyoko, Takahashi, Katsushi, Suzuki, Koji
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container_end_page 710
container_issue 6
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container_title Thrombosis research
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creator Komoriya, Keiji
Inoue, Kyoko
Takahashi, Katsushi
Suzuki, Koji
description 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.
doi_str_mv 10.1016/0049-3848(92)90074-K
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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.</description><subject>activated protein C</subject><subject>Biological and medical sciences</subject><subject>Blood coagulation. 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Psychology</subject><subject>Humans</subject><subject>In Vitro Techniques</subject><subject>Molecular and cellular biology</subject><subject>Oligopeptides</subject><subject>Platelet</subject><subject>platelet aggregation</subject><subject>Platelet Aggregation - drug effects</subject><subject>Platelet Aggregation - physiology</subject><subject>Platelet Aggregation Inhibitors - pharmacology</subject><subject>Protein C - metabolism</subject><subject>Protein C - pharmacology</subject><subject>Prothrombin - metabolism</subject><subject>Prothrombin - pharmacology</subject><subject>thrombin</subject><subject>Thrombin - biosynthesis</subject><subject>Thrombin - pharmacology</subject><issn>0049-3848</issn><issn>1879-2472</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1992</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kcFuGyEQhlHUKHHTvEEicaiq9rAJsLAsl0iV1TZRIuWSnhHLDjbRGlzAlvz2xbGV3noCzXz_aPQNQleU3FBCu1tCuGranvdfFfumCJG8eTxBM9pL1TAu2Qc0e0fO0cecXwmhkipxhs4o50S0YobiQ1j6wZeYdhicA1twdNjY4remwIjXKRbwAc9xDHg91doEBZvFIsHCFF-LPowbW8lhh8sS3gLLFFeDD42NYQup-LDACfYzY_iETp2ZMlwe3wv0--ePl_l98_T862H-_amxXLDSdMKBUIx3dAQgsgcHzHSDrX_BBt65rpfOdo7JnghlCbU9s8PAR8ZN2yloL9CXw9y6z58N5KJXPluYJhMgbrKWbSsYZayC_ADaFHNO4PQ6-ZVJO02J3nvWe4l6L1Erpt8868cauz7O3wwrGP-FDmJr__Oxb7I1k0smWJ_fMc57JiWp2N0Bg-pi6yHpbD2E6tOnegs9Rv__Pf4C8jWbcw</recordid><startdate>19920915</startdate><enddate>19920915</enddate><creator>Komoriya, Keiji</creator><creator>Inoue, Kyoko</creator><creator>Takahashi, Katsushi</creator><creator>Suzuki, Koji</creator><general>Elsevier Ltd</general><general>Elsevier Science</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>19920915</creationdate><title>Inhibitory effect of activated protein C on platelet aggregation induced by the prothrombin-converting reaction</title><author>Komoriya, Keiji ; Inoue, Kyoko ; Takahashi, Katsushi ; Suzuki, Koji</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c452t-65fe592461dee078efe2a6bce0752b46f687fc6f278059c01c82cbb4d24a369e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1992</creationdate><topic>activated protein C</topic><topic>Biological and medical sciences</topic><topic>Blood coagulation. Blood cells</topic><topic>Blood Platelets - drug effects</topic><topic>Blood Platelets - metabolism</topic><topic>Coumarins</topic><topic>Factor Xa - metabolism</topic><topic>Factor Xa - pharmacology</topic><topic>Fluorescent Dyes</topic><topic>Fundamental and applied biological sciences. 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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.</abstract><cop>New York, NY</cop><pub>Elsevier Ltd</pub><pmid>1440535</pmid><doi>10.1016/0049-3848(92)90074-K</doi><tpages>6</tpages></addata></record>
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source MEDLINE; Elsevier ScienceDirect Journals
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
title Inhibitory effect of activated protein C on platelet aggregation induced by the prothrombin-converting reaction
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