Fibrinolysis shutdown phenotype masks changes in rodent coagulation in tissue injury versus hemorrhagic shock.


INTRODUCTION Systemic hyperfibrinolysis (accelerated clot degradation) and fibrinolysis shutdown (impaired clot degradation) are associated with increased mortality compared with physiologic fibrinolysis after 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 3 experimental groups: (1) tissue injury (laparotomy/bowel crush), (2) shock (hemorrhage to mean arterial pressure of 20 mmHg), and (3) control (arterial cannulation and tracheostomy). Baseline and 30-minute postintervention blood samples were collected, and assayed with TEG challenged with taurocholic acid (TUCA). RESULTS Rats were resistant to exogenous tPA; the percent clot remaining 30 minutes after maximum amplitude (CL30) at 150 ng/mL (P = .511) and 300 ng/mL (P = .931) was similar to baseline, whereas 600 ng/mL (P = .046) provoked fibrinolysis. Using the TUCA challenge, the percent change in CL30 from baseline was increased in tissue injury compared with control (P = .048.), whereas CL30 decreased in shock versus control (P = .048). tPA increased in the shock group compared with tissue injury (P = .009) and control (P = .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, whereas shock promotes tPA-mediated fibrinolysis.

DOI: 10.1016/j.surg.2015.04.008
Citations per Year

614 Citations

Semantic Scholar estimates that this publication has 614 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Moore2015FibrinolysisSP, title={Fibrinolysis shutdown phenotype masks changes in rodent coagulation in tissue injury versus hemorrhagic shock.}, author={Hunter B Moore and Ernest Eugene Moore and Peter J. Lawson and Eduardo C Gonzalez and Miguel C Fragoso and Alex P Morton and Fabia Gamboni and Michael P Chapman and Angela Sauaia and Anirban Banerjee and Christopher C. Silliman}, journal={Surgery}, year={2015}, volume={158 2}, pages={386-92} }