DEGR-factor Xa blocks disseminated intravascular coagulation initiated by Escherichia coli without preventing shock or organ damage
| Autor: | F B, Taylor, A C, Chang, G T, Peer, T, Mather, K, Blick, R, Catlett, M S, Lockhart, C T, Esmon |
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| Rok vydání: | 1991 |
| Předmět: |
Dansyl Compounds
Male Platelet Count Tumor Necrosis Factor-alpha Blood Pressure Shock Disseminated Intravascular Coagulation In Vitro Techniques Amino Acid Chloromethyl Ketones Heart Rate Factor Xa Animals Humans Cattle Female Infusions Intravenous Blood Coagulation Escherichia coli Infections Papio |
| Zdroj: | Blood. 78(2) |
| ISSN: | 0006-4971 |
| Popis: | One of the aims of research in the area of thrombosis has been to design an effective anticoagulant that would function in a predictable and direct manner. In evaluating the role of coagulation in sepsis we used factor Xa blocked in the active center with [5-(dimethylamino)1-naphthalenesulfonyl]-glutamylglycylarginyl+ ++ chloromethyl ketone (DEGR-Xa). We infused 1 mg/kg of DEGR-Xa together with LD100 concentrations of Escherichia coli (4 x 10(10) organisms/kg) into five baboons. As controls, we infused E coli alone into five baboons. The inflammatory, coagulant, and cell injury responses to E coli of both the treated and control groups were lethal and were similar in every respect except for the complete inhibition of the consumption of fibrinogen in the DEGR-Xa group. The half life of DEGR-Xa was approximately 10 hours and 2 hours, as determined by isotopic and enzyme-linked immunosorbent assays, respectively. These results for the first time demonstrate that, although coagulation occurs in E coli sepsis, fibrin formation per se did not influence the lethal outcome in this model. These results also show the effectiveness of DEGR-Xa as an anticoagulant and raise the possibility that it could serve as an alternative to anticoagulants currently in use. |
| Databáze: | OpenAIRE |
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