Activation and inhibition of fibrinolysis in septic patients in an internal intensive care unit

Abstract

Disseminated thrombotic processes in the microcirculation are considered to be an important cause of multiple organ failure in septic patients. Fibrinolysis is one endogenous mechanism protecting the circulation from overwhelming thrombosis. Therefore, we looked for alterations of fibrinolytic parameters (tissue plasminogen activator (t-PA), tissue plasminogen activator inhibitor (PAI), D-dimer, euglobulin-clot-lysis-time (ECLT), plasminogen, alpha 2-antiplasmin) and of some coagulation parameters (prothrombin time, fibrinogen, platelets, antithrombin III, protein C, factor XII) in clearly defined septic patients and for the relations of these values to the severity of the disease (APACHE II-score). An increase in D-dimer and t-PA-antigen was registered in all patients, while factor XII and plasminogen were decreased, indicating an activated fibrinolysis. In contrast the systemic fibrinolytic capacity of the blood was strongly inhibited: t-PA-activity was not detectable, PAI-function was elevated, the ECLT was prolonged and alpha 2-antiplasmin was normal. Coagulation was moderately activated: the platelets, antithrombin III and protein C were decreased, the prothrombin time was prolonged and fibrinogen was normal. The changes in t-PA-antigen, PAI-function, factor XII, prothrombin time and antithrombin III were significantly related to the APACHE II-score of the patients. We conclude that the activation of coagulation is accompanied by an activation of fibrinolysis in the microcirculation, but that systemically the increased inhibitors of fibrinolysis (PAI, alpha 2-antiplasmin) induce a decrease of the fibrinolytic capacity of the blood. The severity of the disease determines the extent of the alterations.

Coagulation, Fibrinolytic and Kallikrein Systems in Neonates with Uncomplicated Sepsis and Septic Shock

“…Fibrinolysis activation had been reported in patients with severe sepsis [28], We have found similar changes in our ill newborns, with an elevation of t-PA and PAI-1 levels. While the decrease in plasminogen levels sug gests a depletion of this factor, the normal antiplasmin values were compatible with sys temic inhibition of fibrinolysis or with an acute-phase response, as it has been pre viously reported by others [29], In our study, PAI-1 levels increased.…”

Immunohematologic characteristics of infection-associated cerebral infarction.

“…[6][7] As a group, stroke patients with infection had an increased level of fibrin D-dimer, indicating some procoagulant tendencies. To place these fibrin D-dimer levels into context, our patients with infectionassociated stroke had levels roughly comparable to those of other recently reported stroke 7 and myocardial infarction 13 cohorts; these fibrin D-dimer levels were, however, substantially lower than those of a group of septic patients hospitalized in an intensive care unit. 13 It is uncertain whether patients without stroke and with the generally mild infections of the current study might have similar hemostatic findings.…”

“…Hemostasis alterations are known to be present in both patients with stroke 6 -7 and patients with infection, particularly sepsis and other severe infections. 12 " 13 This has led us and others 14 to postulate that altered coagulation may represent a link between infection and stroke, perhaps via cytokines (e.g., interleukin-1 and rumor necrosis factor) known to have procoagulant effects. 14 - 17 In our series of patients with cerebral infarction, 34% (17 of 50) had evidence of infection, most commonly relatively mild respiratory infections, ^1 month before the stroke.…”

Interférences avec l’hémostase

“…Cette insuffi sance est secondaire à la présence de cytokines pro-infl ammatoires comme le TNF_ et l'interleukine 1. La consommation de plasminogène et d'_-2 antiplasmine est responsable d'une baisse de leur taux corrélée à la gravité du sepsis [17]. Alors que le taux de t-PA diminue, le taux de PAI-1 s'élève progressivement pour atteindre un plateau de plusieurs heures contribuant à une inhibition complète de la fi brinolyse.…”