title: Massive amounts of tissue factor induce fibrinogenolysis without tissue hypoperfusion in rats.
abstract: Trauma-induced tissue factor (TF) release into the systemic circulation is considered to play an important role in the development of disseminated intravascular coagulation (DIC) immediately after severe trauma. However, the relationship between TF and hyperfibrinolysis, especially fibrinogenolysis, has been unclear. A total of 18 rats were divided into three groups: (a) the control group was infused with normal saline; (b) the low-dose group was infused with 4 U/kg TF; and (c) the high-dose group was infused with 16 U/kg TF. Arterial blood was drawn immediately and 2 and 4 h after the start of TF infusion. At each sampling point, arterial blood gases, platelet counts, and coagulation variables were measured. The fibrinogen degradation products were evaluated by a Western blot analysis. Hypotension, hypoxemia, and lactic acidosis were not observed in any of the three groups. In proportion to the doses of TF, the platelet counts, coagulation, and fibrinolysis variables deteriorated in line with DIC. The α2-plasmin inhibitor levels significantly decreased in the high-dose group compared with the other groups. The amounts of fibrinogen degradation products increased in proportion to the doses of TF. The plasmin-α2-plasmin inhibitor complex level in the high-dose group increased more than that of the other groups. In conclusion, TF can induce DIC associated with fibrinolysis and fibrinogenolysis without tissue hypoperfusion. The decrease in the α2-plasmin inhibitor level and the significant increase in the plasmin level may be the two main factors underlying the pathogenesis of hyperfibrin(ogen)olysis after TF administration.
authors.affiliation: Division of Acute and Critical Care Medicine, Department of Anesthesiology and Critical Care Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan. mineji@dream.com
authors.forename: Mineji
authors.initials: M
authors.lastname: Hayakawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Gando
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ieko
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Honma
authors.forename: Taeko
authors.initials: T
authors.lastname: Homma
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Yanagida
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Kubota
authors.forename: Shinji
authors.initials: S
authors.lastname: Uegaki
authors.forename: Atsushi
authors.initials: A
authors.lastname: Sawamura
authors.forename: Hidesaku
authors.initials: H
authors.lastname: Asakura
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D004211:Disseminated Intravascular Coagulation / Q000097:blood* / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects*; D006454:Hemoglobins / Q000378:metabolism; D008297:Male; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D010976:Platelet Count; D051381:Rats; D017208:Rats, Wistar; D013925:Thromboplastin / Q000008:administration & dosage / Q000494:pharmacology*; D000979:alpha-2-Antiplasmin / Q000378:metabolism
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; D006454:Hemoglobins; D000979:alpha-2-Antiplasmin; D005340:Fibrinogen; D013925:Thromboplastin; D010100:Oxygen