Human Antithrombin Concentrates and Experimental Disseminated Intravascular Coagulation

Abstract

The effect of human antithrombin III concentrates was studied in a dog model in which DIC was produced by the infusion of 0.66 M lactic acid. In 35 animals infused with lactic acid only, platelet counts, fibrinogen levels, alpha 2-antiplasmin levels, and antithrombin levels decreased significantly over a 4-hour observation period. At the same time, the levels of fibrin(ogen) split products increased. At the end of the experimental period, the glomeruli of the dogs' kidneys contained significant quantities of fibrin. Hemodynamically, the dogs experienced a significant decrease in cardiac output, whereas the mean arterial blood pressures remained unchanged. Urine output seemed to decline during the time of study. Appreciable quantities of heparin could be measured in the dogs' plasmas. In 13 dogs that were treated in the same manner as the just described 35 animals, 1 U of human antithrombin concentrate per ml of calculated dog plasma was infused over a 90-minute time span, beginning after 1 hour of acidosis. Although no differences were noted in the decrease in platelet counts between the two groups, fibrinogen levels and alpha 2-antiplasmin levels declined less drastically in the antithrombin-treated group. Also the levels of fibrin(ogen) split products increased less in the treated group. The antithrombin activity levels increased markedly and remained at their high levels even after the infusion of antithrombin had ceased. The amount of human antithrombin circulating was followed by immunologic assays using a human antibody to antithrombin. Also, with this technique, the levels of infused antithrombin did not decrease. The amount of fibrin found in the glomeruli of this group of animals was significantly lower than in the nontreated group (p less than 0.001). Even cardiac output was higher in the treated group and urine production seemed to increase. Also, these dogs had appreciable quantities of heparin in their plasmas. In a control group of six animals who were infused with saline instead of lactic acid, no major changes were observed in the coagulation and cardiovascular parameters. These data seem to suggest that antithrombin concentrates exert a certain protective effect in this particular DIC animal model.