Introduction
Systemic hyperfibrinolysis (accelerated clot degradation) and fibrinolysis shutdown (impaired clot degradation) are associated with increased mortality compared to physiologic fibrinolysis following trauma. Animal models have not reproduced these changes. We hypothesize rodents have a shutdown phenotype that require an exogenous profibrinolytic to differentiate mechanisms that promote or inhibit fibrinolysis.
Methods
Fibrinolysis resistance was assessed by thrombelastography (TEG) using exogenous tissue plasminogen activator (tPA) titrations in whole blood. There were three experimental groups: 1)tissue injury (laparotomy/bowel crush), 2)shock (hemorrhage to mean arterial pressure 20 mmHg), and 3)control (arterial cannulation and tracheostomy). Baseline and 30-minute post-intervention blood samples were collected, and assayed with TEG challenged with taurocholic acid (TUCA).
Results
Rats were resistant to exogenous tPA; CL30 (Percent clot remaining 30 minutes after maximum amplitude) at 150ng/ml (p=0.511) and 300ng/ml (p=0.931) was similar to baseline, while 600ng/ml (p=0.046) provoked fibrinolysis. Using the TUCA challenge, the percent change in CL30 from baseline was increased in tissue injury compared to control (p=0.048.), whereas CL30 decreased in shock versus control (p=0.048). TPA increased in the shock group compared to tissue injury (p=0.009) and control (p=0.012).
Conclusion
Rats have an innate fibrinolysis shutdown phenotype. The TEG TUCA challenge is capable of differentiating changes in clot stability with rats undergoing different procedures. Tissue injury inhibits fibrinolysis while shock promotes tPA-mediated fibrinolysis.
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