The effect of fibrinogen concentrate administration on coagulation abnormalities in a rat sepsis model.
Disseminated intravascular coagulation is a disorder that affects the function of the clotting system and is frequently associated with sepsis or septic shock. One of its leading symptoms is the decrease in circulating fibrinogen. We investigated the effect of fibrinogen concentrate (Haemocomplettan P) on fibrinogen plasma levels, coagulation parameters and mortality in a rat model of sepsis-induced disseminated intravascular coagulation. The disseminated intravascular coagulation was characterized by elevated thrombin-antithrombin complex and a sharp drop in circulating fibrinogen. Coagulation abnormalities were evaluated by thrombelastography. Plasma fibrinogen levels decreased from 2.06 +/- 0.2 to 0.16 +/- 0.1 g/l following administration of bacterial lipopolysaccharide. Thrombelastographic measurements revealed a concurrent decrease in maximum amplitude and an increase in reaction time. Treatment with fibrinogen concentrate (Haemocomplettan P, 25-200 mg/kg body weight intravenously) resulted in a statistically significant dose-dependent increase in fibrinogen plasma levels and amelioration of the measured coagulation abnormalities. Fibrinogen plasma concentrations were restored to normal levels when 200 mg/kg body weight fibrinogen concentrate was administered. A significant decrease in sepsis-induced mortality was observed in animals treated with Haemocomplettan P.
Kaspereit
Franz
F
Aventis Behring GmbH, Pharmacology/Toxicology, Marburg, Germany.
Doerr
Baerbel
B
Dickneite
Gerhard
G
D000818:Animals; D000990:Antithrombin III; D001777:Blood Coagulation; D004195:Disease Models, Animal; D005260:Female; D005340:Fibrinogen / Q000008:administration & dosage* / Q000032:analysis*; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity; D010447:Peptide Hydrolases / Q000097:blood*; D010949:Plasma / Q000737:chemistry; D051381:Rats; D012772:Shock, Septic / Q000097:blood* / Q000139:chemically induced / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D013916:Thrombelastography
D008070:Lipopolysaccharides; C046193:antithrombin III-protease complex; D000990:Antithrombin III; D005340:Fibrinogen; D010447:Peptide Hydrolases