E. Gonzalez1, H. B. Moore1, M. P. Chapman1, M. Fragoso1, A. P. Morton1, C. C. Silliman1,2, A. Banerjee1, E. E. Moore1,3 1University Of Colorado Denver,Department Of Surgery,Aurora, CO, USA 2Bonfils Blood Center,Department Of Researcj,Denver, CO, USA 3Denver Health Medical Center,Department Of Surgery,Denver, CO, USA
Introduction: The fibrinolytic response to trauma and hemorrhagic shock has been thus far characterized as a hyper-fibrinolytic state, which exacerbates coagulopathic bleeding. However, recently we have identified a subpopulation of patients with impaired fibrinolysis, also referred to as fibrinolysis shutdown, which favors unregulated clotting, particularly in the microvasculature. This spectrum of fibrinolysis may occur with simultaneous heterogeneity throughout tissue beds. We hypothesized that the response to ischemia is organ specific, with distinct patterns of fibrinolysis.
Methods: Six Yorkshire swine were anesthetized, and after laparotomy, the kidney, small bowel, liver, and spleen were subjected to controlled ischemia by arterial clamping. Venous samples were obtained from these organs at baseline (before ischemia), then at 15 and 30 min. after clamping, and 5 min. after reperfusion. A systemic sample from the saphenous vein was also obtained at theses time points. A systemic mean arterial pressure of 35 mmHg was induced after clamping during this period of time. Thrombelastography (TEG) was performed from re-calcified citrated samples between 20-40 min. from collection. Changes in TEG variables for each organ along these time-points were compared by the Friedman test for significance (p<0.05), with post-hoc pairwise comparisons (Bonferroni adjusted p-value).
Results: The TEG variables R-time, alpha-angle, and maximal amplitude (MA), all progressively demonstrated a coagulopathic profile with ischemia time, and did not normalize after reperfusion, for all organs and for the systemic venous samples. Fibrinolysis quantified by TEG (%LY30: percent of clot lysis 30 min. after reaching MA) progressively decreased with ischemia, demonstrating fibrinolysis shutdown; this was statistically significant for the kidney and liver (Fig. 1). However, the systemic venous samples demonstrated hyper-fibrinolysis proportional to ischemia time, which was also statistically significant. All organs had statistically significantly less fibrinolysis than the systemic venous sample at 15 min. and 30 min. of ischemia, and after reperfusion (Fig. 1).
Conclusion: Despite evidence of systemic hyper-fibrinolysis during shock, paradoxically, fibrinolysis shutdown occurs simultaneously at an organ level, particularly in the kidney and liver. Consequently, treatment of hyperfibrinolysis with anti-fibrinolytics, such as tranexamic acid, may have adverse effects in certain organs’ microvasculature. These differences in the spectrum of fibrinolysis provide further insight into the pathophysiology of trauma-induced coagulopathy, allowing for study of its optimal diagnosis and management.
