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  • 标题:In vitro and in vivo correlation of clotting protease activity: Effect of heparin
  • 本地全文:下载
  • 作者:Sanford N. Gitel ; Ronald C. Stephenson ; Stanford Wessler
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:1977
  • 卷号:74
  • 期号:7
  • 页码:3028-3032
  • DOI:10.1073/pnas.74.7.3028
  • 语种:English
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:The thrombogenicity of three highly purified proteases (thrombin, activated Factor X, and activated Factor IX) was determined quantitatively in an animal model. The minimal amounts required to produce a standard score 4 thrombus were 1.1 nmol for thrombin, 0.12 nmol for activated Factor X, and 0.018 nmol for activated Factor IX. After the administration of heparin at 5, 10, and 20 units/kg in rabbits, the thrombogenicity of each of these proteases decreased progressively. The heparin-induced inhibition of thrombosis decreased in the order, activated Factor IX > activated Factor X > thrombin at each heparin concentration. These differences were statistically significant. These in vivo data provide support for the following hypotheses originally developed from in vitro experiments: (i) activation of the blood coagulation system, which proceeds through a cascade mechanism, incorporates biochemical amplification; (ii) the inhibition of activated Factor IX by antithrombin III in the presence of heparin is an important reaction in the prevention of thrombosis; (iii) less heparin is required to inhibit thrombosis prior to thrombin generation than afterward; (iv) an increase in the reactivity of antithrombin III reflects a decreased tendency to thrombosis while a decrease in this reactivity reflects an increased tendency to thrombosis.
  • 关键词:coagulation ; antithrombin III ; animal model
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