Activation patterns of coagulation and fibrinolysis in baboons following infusion with lethal or sublethal dose of Escherichia coli.
Administration of low doses endotoxin or tumor necrosis factor (TNF) in human experimental models for sepsis results in transient activation of both coagulation and fibrinolysis and subsequent inhibition of the fibrinolytic system by plasminogen activator inhibitor type 1 (PAI-1). We have investigated in a baboon model for sepsis, whether administration of a lethal or sublethal dose of living E. coli could induce similar activation patterns. Levels of thrombin-antithrombin III (TAT) complexes increased significantly to zeniths of 425 and 33 times the baseline values at t+360 in the lethal and sublethal group, respectively. Activation of fibrinolysis, as reflected by plasmin-alpha 2 antiplasmin (PAP) complexes, in the sublethal group was maximal at t+60 and was increasingly inhibited thereafter in spite of a sustained increase of tissue type plasminogen activator (t-PA) levels. In the lethal group PAP complexes increased to a zenith of 38 times the baseline values at t+240. PAI-1 levels increased to 15 times the baseline values at t+360 in the sublethal group, whereas in the lethal group they increased almost linearly to 20 times the baseline values at t+360. Despite high levels of PAI-1, effective inhibition of the fibrinolysis was not established until at T+240 in the lethal group. The difference in activation patterns of both mediator systems in the sublethal and lethal group of baboons indicate that extensive activation of coagulation contributes to the lethal complications in sepsis.
de Boer
J P
JP
Central Laboratory of the Netherlands Red Cross Blood Transfusion Services, Amsterdam.
Creasy
A A
AA
Chang
A
A
Roem
D
D
Brouwer
M C
MC
Eerenberg
A J
AJ
Hack
C E
CE
Taylor
F B
FB
D000818:Animals; D000933:Antifibrinolytic Agents; D001777:Blood Coagulation; D004927:Escherichia coli Infections / Q000097:blood* / Q000503:physiopathology; D005341:Fibrinolysin / Q000032:analysis; D005342:Fibrinolysis; D006439:Hemodynamics; D006801:Humans; D010215:Papio; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D010959:Tissue Plasminogen Activator / Q000097:blood; D000979:alpha-2-Antiplasmin / Q000032:analysis
D000933:Antifibrinolytic Agents; D017395:Plasminogen Activator Inhibitor 1; D000979:alpha-2-Antiplasmin; C037742:plasmin-plasmin inhibitor complex; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin