The effects of antithrombin III, heparin and a novel heparinoid infusions on the bleeding tendency using an experimental model in the rat.
The effects of selective increase of plasma AT-III concentration (to 2 U/ml and 8 U/ml) in the presence or absence of low dose commercial heparin and a novel natural heparinoid (Org 10172) on APTT, clotting factors and bleeding were investigated in an experimental model in rats. Slight increases in the APTT were observed with: a. Org 10172, b. both AT-III doses and c. combinations hereoff. However, synergism was observed in the prolongations of the APTT when the AT-III concentrate (70 U/kg and 500 U/kg) was combined with both heparin dosages. AT-III concentrates (70 U/kg and 500 U/kg) or Org 10172 (2,5 mg/kg) separately or in combination showed no effect on bleeding. Heparin (0, 125 and 0,25 mg/kg i.v.) also showed no effect on bleeding neither if they were combined with the lower dose AT-III. However, heparin (both dosages) combined with 500 U/kg of AT-III concentrates significant increased blood loss. These observations suggest that infusion of AT-III concentrate additionally to low dose heparin therapy did not increase bleeding in the rat model used provided that extreme high AT-III plasma levels (8 U/ml) were avoided. The novel natural heparinoid Org 10172 alone or combined with either AT-III dosage induced no increased bleeding.
D000818:Animals; D000990:Antithrombin III / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects*; D004195:Disease Models, Animal; D004211:Disseminated Intravascular Coagulation; D006470:Hemorrhage / Q000188:drug therapy; D006493:Heparin / Q000494:pharmacology*; D006496:Heparinoids / Q000494:pharmacology*; D008297:Male; D009135:Muscular Diseases / Q000188:drug therapy; D051381:Rats; D011919:Rats, Inbred Strains
D006496:Heparinoids; D000990:Antithrombin III; D006493:Heparin