title: Formation of fibrin monomers in experimental disseminated intravascular coagulation and its inhibition by recombinant hirudin.
abstract: An experimental disseminated intravascular coagulation (DIC) was induced in female CD rats by the intravenous administration of living bacteria (9.5 x 10(7) cfu Klebsiella pneumoniae), sublethal (5 mg/kg) or lethal (50 mg/kg) lipopolysaccharide (LPS), or tissue factor (1.5 micrograms/kg i.v. bolus or 0.4 micrograms/kg x hr i.v. infusion). We used a new fibrin monomer (FM) assay to follow the course of DIC. FM were detected by their ability to stimulate the tissue-type (t-PA) plasminogen activator dependent conversion of plasminogen to plasmin by a chromogenic assay. Miniplasminogen was used instead of plasminogen to avoid interference of the assay by alpha 2-antiplasmin. As a marker of DIC, elevated levels of FM were observed with all DIC-inducing agents (plasma levels were up to 90 micrograms/ml). The kinetics of FM formation were similar to the course of thrombin-antithrombin III (TAT) levels (maximal plasma levels 70 ng/ml); however, in the bacterial infection group, both parameters rose after a lag phase of about 1 hr. A 4 hr infusion of the highly specific thrombin inhibitor recombinant (rec.) hirudin (0.125 mg/kg x hr) resulted in a decrease of FM levels from 89.2 +/- 14.4 micrograms/ml in the LPS group (n = 10) to 27.4 +/- 11.2 micrograms/ml in the rec. hirudin group (n = 10; P < 0.001). The respective values for TAT levels were 73.1 +/- 19.7 micrograms/ml in the LPS group and 52.7 +/- 15.7 ng/ml in the rec. hirudin group (P < 0.001). Other coagulation parameters, such as platelets, fibrinogen, and fibrin(ogen) degradation products, were ameliorated accordingly.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Research Laboratories of Behringwerke AG, Marburg, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Dickneite
authors.forename: J
authors.initials: J
authors.lastname: Czech
authors.forename: H
authors.initials: H
authors.lastname: Keuper
mesh_terms: D000818:Animals; D000990:Antithrombin III / Q000378:metabolism; D004211:Disseminated Intravascular Coagulation / Q000097:blood* / Q000139:chemically induced / Q000401:mortality; D005260:Female; D005337:Fibrin / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D006629:Hirudins / Q000494:pharmacology*; D008070:Lipopolysaccharides; D010447:Peptide Hydrolases / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins; D016019:Survival Analysis; D013997:Time Factors
chemical_list: D006629:Hirudins; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; C046193:antithrombin III-protease complex; D000990:Antithrombin III; D005337:Fibrin; D010447:Peptide Hydrolases