Tissue injury suppresses fibrinolysis after hemorrhagic shock in nonhuman primates (rhesus macaque)

Background Hypoperfusion is associated with hyperfibrinolysis and early death from exsanguination, whereas tissue trauma is associated with hypofibrinolysis and delayed death from organ failure. We sought to elucidate the effects of injury patterns on fibrinolysis phenotypes using a nonhuman primate (NHP) model. Methods NHPs were randomized to three injury groups (n = 8/group): 60 minutes severe pressure-targeted controlled hemorrhagic shock (HS); HS + soft tissue injury (HS+); or HS + soft tissue injury + femur fracture (HS++). Animals were resuscitated and monitored for 360 minutes. Blood samples were collected at baseline, end-of-shock, end-of-resuscitation (EOR), and T = 360 minutes for assessments of: severity of shock (lactate) and coagulation via prothrombin time, partial thromboplastin time, D-dimer, fibrinogen, antithrombin-III, von Willebrand factor, and viscoelastic testing (ROTEM). Results are reported as mean ± SEM; statistics: two-way analysis of variance and t-tests (significance: p < 0.05). Results Blood loss, prothrombin time, partial thromboplastin time, antithrombin-III, fibrinogen, and von Willebrand factor were equivalent among groups and viscoelastic testing revealed few differences throughout the study. D-dimer increased approximately threefold, at EOR in the HS group, and at T = 360 minutes in the HS+ and HS++ groups (p < 0.05). At EOR, in the HS group compared with the HS+ and HS++ groups; the D-dimer-lactate ratio was twofold greater (2.2 ± 0.3 vs. 1.1 ± 0.3 and 1.1 ± 0.2, respectively; p < 0.05) and tissue factor-activated fibrin clot 30-minute lysis index was lower (98 ± 1% vs. 100 ± 0% and 100 ± 0%, respectively; p < 0.05). Conclusion NHPs in HS exhibit acute suppression of fibrinolysis in the presence of tissue injury. Additional assessments to more comprehensively evaluate the mechanisms linking tissue injury with the observed fibrinolysis shutdown response are warranted.