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Effects of human antithrombin III (at III) and heparin on endotoxin-induced disseminated intravascular coagulation (DIC) in rabbits
58
THROMBOSIS RESEARCH
Suppl. VI,
1986
112
TURNOVER OF ANTITHROMBIN III AND HEPARIN COFACTOR II IN BABOONS TREATED WITH HEPARIN AND PENTOSAN POLYSULFATE. P. Sic, J. Lansen, B. Verschuere, P. Vie, B. Boneu. Lab. Hemostase, Hop. Purpan, Toulouse France ; Sanofi-Recherche, Montpellier France. Antithrombin III (AT III) and heparin cofactor II (HC II) are two heparin-dependent inhibitors of thrombin. At therapeutic concentrations in plasma, heparin (Hep) and pentosan polysulfate (PPS) essentially interact with AT III and HC II respectively. The aim of this work was to study the influence of Hep and PPS on the turnover of each inhibitor. T III and HC II were enzymatically labelled their of with p"l;ag' kedaZmaf3% respectively without loss their activities and without alteration of antithrombin crossed and PPS as studied by affinities for Hep immunoelectrophoresis and by*chroma$gp:aphy on Hep-sepharose. - AT III (8 uci/kg) and 555"' the simultaneous injection of I- HC II (4 uci/kg), nine baboons were randomly allocated to 3 groups receiving for 8 days subcutaneous Hep (500 IU/kg/d), PPS (5 mg/kg/d) or saline. The half-life (elimination curve) ranges in the placebo group were 49-52 h for AT III and 46-53 h for HC II. They were not significantly different in the treated groups. The half-lives of the 2 inhibitors were strongly correlated in individual animals (p
113 EFFECTS OF HUMAN ANTITHROMBIN III (AT III) AND HEPARIN ON ENDOTOXIN-INDUCED DISSEMINATED INTRAVASCULAR COAGULATION (DIC) IN RABBITS.E.Rocha,C.Gmez, J.A.PZiramo,J.Acosta*, B.Cuesta, J.Fern&dez, A. Aranda. Hematology Service, University of Navarra and Research Department of Landerlan Laboratories*. 31080-Pamplona. Spain. DIC was induced in 84 rabbits by infusion with 20yg/kg/hr of E.Coli endotoxin for 6 hr: 11 rabbits received no treatment; 25 received heparin (S-20 U/kg/hr) IV; 32 received AT III (lo-40 U/kg/hr or 240 U/kg bolus dose) IV; 16 rabbits received heparin plus AT III. Treatment was started simultaneously with endotoxin infusion. Blood samples were obtained before and at 2 and 6 hr during endotoxin infusion to measure platelet count, prothrombin, thrombin and partial thromboplastin time, fibrinogen, factors V, VIII, XII, AT III, fibrin monomers and fibrinogen degradation products (FDP). Rabbits were sacrificed 2 hr following end of endotoxin infusion to study fibrin deposits. Heparin, AT III and heparin-AT III were found to reduce the endotoxin-induced increase in FDP. Moreover, AT III prevented the decrease of f XII and the increase of fibrin monomers. Heparin-AT III and AT III bolus dose succesfully reduced fibrin deposits in kidneys and lungs. Mortality decreased significantly (p (0.003) in all treated groups, and was associated with lower levels of f XII and AT III and higher levels of fibrin monomers and FDP. We conclude that although AT III and/or heparin only slightly reduce the severity of DIC, they significantly reduce fibrin deposits and DIC-associated mortality.
THROMBOSIS RESEARCH
Suppl. VI,
1986
112
TURNOVER OF ANTITHROMBIN III AND HEPARIN COFACTOR II IN BABOONS TREATED WITH HEPARIN AND PENTOSAN POLYSULFATE. P. Sic, J. Lansen, B. Verschuere, P. Vie, B. Boneu. Lab. Hemostase, Hop. Purpan, Toulouse France ; Sanofi-Recherche, Montpellier France. Antithrombin III (AT III) and heparin cofactor II (HC II) are two heparin-dependent inhibitors of thrombin. At therapeutic concentrations in plasma, heparin (Hep) and pentosan polysulfate (PPS) essentially interact with AT III and HC II respectively. The aim of this work was to study the influence of Hep and PPS on the turnover of each inhibitor. T III and HC II were enzymatically labelled their of with p"l;ag' kedaZmaf3% respectively without loss their activities and without alteration of antithrombin crossed and PPS as studied by affinities for Hep immunoelectrophoresis and by*chroma$gp:aphy on Hep-sepharose. - AT III (8 uci/kg) and 555"' the simultaneous injection of I- HC II (4 uci/kg), nine baboons were randomly allocated to 3 groups receiving for 8 days subcutaneous Hep (500 IU/kg/d), PPS (5 mg/kg/d) or saline. The half-life (elimination curve) ranges in the placebo group were 49-52 h for AT III and 46-53 h for HC II. They were not significantly different in the treated groups. The half-lives of the 2 inhibitors were strongly correlated in individual animals (p
113 EFFECTS OF HUMAN ANTITHROMBIN III (AT III) AND HEPARIN ON ENDOTOXIN-INDUCED DISSEMINATED INTRAVASCULAR COAGULATION (DIC) IN RABBITS.E.Rocha,C.Gmez, J.A.PZiramo,J.Acosta*, B.Cuesta, J.Fern&dez, A. Aranda. Hematology Service, University of Navarra and Research Department of Landerlan Laboratories*. 31080-Pamplona. Spain. DIC was induced in 84 rabbits by infusion with 20yg/kg/hr of E.Coli endotoxin for 6 hr: 11 rabbits received no treatment; 25 received heparin (S-20 U/kg/hr) IV; 32 received AT III (lo-40 U/kg/hr or 240 U/kg bolus dose) IV; 16 rabbits received heparin plus AT III. Treatment was started simultaneously with endotoxin infusion. Blood samples were obtained before and at 2 and 6 hr during endotoxin infusion to measure platelet count, prothrombin, thrombin and partial thromboplastin time, fibrinogen, factors V, VIII, XII, AT III, fibrin monomers and fibrinogen degradation products (FDP). Rabbits were sacrificed 2 hr following end of endotoxin infusion to study fibrin deposits. Heparin, AT III and heparin-AT III were found to reduce the endotoxin-induced increase in FDP. Moreover, AT III prevented the decrease of f XII and the increase of fibrin monomers. Heparin-AT III and AT III bolus dose succesfully reduced fibrin deposits in kidneys and lungs. Mortality decreased significantly (p (0.003) in all treated groups, and was associated with lower levels of f XII and AT III and higher levels of fibrin monomers and FDP. We conclude that although AT III and/or heparin only slightly reduce the severity of DIC, they significantly reduce fibrin deposits and DIC-associated mortality.