Fibrinolytic system activation immediately following trauma was quickly and intensely suppressed in a rat model of severe blunt trauma

Abstract

In severe trauma, excessive fibrinolytic activation is associated with an increase in the transfusion volume and mortality rate. However, in the first several hours after a blunt trauma, changes in fibrinolytic activation, suppression, and activation–suppression balance have not yet been elucidated, which the present study aimed to clarify. Anesthetized 9-week-old male Wistar S/T rats experienced severe blunt trauma while being placed inside the Noble–Collip drum. Rats were randomly divided into four groups of seven. The no-trauma group was not exposed to any trauma; the remaining groups were analysed 0, 60, and 180 min after trauma. Immediately following trauma, total tissue-plasminogen activator (tPA) levels significantly increased in the plasma, and the balance of active tPA and active plasminogen activator inhibitor-1 (PAI-1) significantly tipped toward fibrinolytic activation. After trauma, both tPA and PAI-1 levels increased gradually in various organs and active and total PAI-1 levels increased exponentially in the plasma. Total plasma tPA levels 60 min after trauma returned quickly to levels comparable to those in the no-trauma group. In conclusion, fibrinolytic activation was observed only immediately following trauma. Therefore, immediately after trauma, the fibrinolytic system was activated; however, its activation was quickly and intensely suppressed.

Characterization and Usefulness of Clot-Fibrinolysis Waveform Analysis in Critical Care Patients with Enhanced or Suppressed Fibrinolysis

“…For example, in patients with trauma and out-ofhospital cardiac arrest, strong fibrinolytic activation is frequently observed on arrival at the emergency department. [30][31][32][33][34] The fibrinolytic activation in patients with outof-hospital cardiac arrest is induced by the massive release of tPA, with a level up to 250 times that of healthy individuals. 31 Fig.…”

“…For example, in patients with trauma and out-of-hospital cardiac arrest, strong fibrinolytic activation is frequently observed on arrival at the emergency department. 30 31 32 33 34 The fibrinolytic activation in patients with out-of-hospital cardiac arrest is induced by the massive release of tPA, with a level up to 250 times that of healthy individuals. 31 In patients with severe trauma, marked fibrinolytic activation is observed, but the total tPA concentration is increased by only approximately 30 times that in healthy individuals.…”

“…Understanding the fibrinolysis situation is important for the diagnosis and treatment of critically ill patients because strong fibrinolytic activation is observed in various clinical settings. For example, in patients with trauma and out-of-hospital cardiac arrest, strong fibrinolytic activation is frequently observed on arrival at the emergency department (30)(31)(32)(33)(34) . The fibrinolytic activation in patients with out-of-hospital cardiac arrest is induced by the massive release of tPA, with a level up to 250 times that of healthy individuals (31) .…”

Resuscitative Endovascular Balloon Occlusion of the Aorta: Zone 1 Reperfusion-Induced Coagulopathy

“…The hyperfibrinolysis associated with Zone 1 may be aggravated by endothelial activation following ischemia leading to tPA release and further accentuated by decreased tPA clearance from the liver. Polytrauma in rodent models show that tPA release occurs immediately after insult, and PAI-1 release occurs several hours later (35,36). Our tPA and PAI-1 findings are consistent with these observations.…”

Advances in the Management of Coagulopathy in Trauma: The Role of Viscoelastic Hemostatic Assays across All Phases of Trauma Care

“…Further studies to validate these newer fibrinolytic diagnostic assays and their ability to guide therapies (e.g., selective TXA use) are needed, and a focus on the molecular mechanisms (e.g., PAI-1 depletion or abundance) is needed to help advance our understanding as new treatment options are explored. 137,138 PAI-1 has been long appreciated as an acute phase reactant protein that increased following hemorrhagic shock. 139 PAI-1 appears to be the first phase of shutting down the fibrinolytic system, and when its levels have been depleted, hyperfibrinolysis occurs.…”