A. P. Morton3, H. B. Moore3, E. Gonzalez3, G. Wiener3, P. Lawson2, M. Chapman3, C. Silliman3, E. Peltz1,3, A. Banerjee3, E. E. Moore2,3 1University Of Colorado Hospital,Surgery,Aurora, CO, USA 2Denver Health Medical Center,Surgery,Denver, CO, USA 3University Of Colorado School Of Medicine,Surgery,Aurora, CO, USA
Introduction: Hyperfibrinolysis plays an integral role in the genesis of trauma induced coagulopathy (TIC). Recent data demonstrates that red blood cell (RBC) lysis promotes fibrinolysis; however, the mechanism is unclear. Hemoglobin-based oxygen carriers (HBOC) have been developed for resuscitation and have been associated with coagulopathy. We hypothesize that replacement of whole blood (WB) using an HBOC results in a coagulopathy due to the presence of free hemoglobin.
Methods: Whole blood was sampled from healthy donors (n=6). The clotting profile of each citrated sample was evaluated using native thromboelastography (TEG). Serial titrations were performed using both HBOC (Polyheme) and normal saline (NS) (5%, 25%, and 50%) and evaluated both with and without a 75 ng/microliter tissue-plasminogen activator (tPA) challenge. Tranexamic acid (TXA) was added to inhibit plasmin dependent fibrinolysis. Fibrinolysis was measured and recorded as LY30, the percentage of clot lysis at 30 minutes after maximal clot strength. Statistics were calculated using SPSS software. Dilution of WB with NS or HBOC was correlated using LY30 via Spearman Rho coefficients. Groups were also compared using a Friedman test and post-hoc analysis with a Bonferroni adjustment.
Results: TPA-provoked fibrinolysis was enhanced by both HBOC (median LY30 at 5%, 25%, 50% titrations: 11%, 21%, 44%; Spearman=0.94; p<0.001) and NS (11%, 28%, 58%; Spearman=0.790; p<0.001). However, HBOC also enhanced fibrinolysis without the addition of tPA (1%,4%,5%; Spearman=0.735; p=0.001) and NS did not (1%,2%,1%; r=0.300; p=0.186; Figure 1). Moreover, addition of TXA did not alter or inhibit this fibrinolysis (WB vs 50% HBOC: 1.8% vs 5.65%, p=0.04). There was no significant difference in fibrinolysis of HBOC with or without TXA (50% HBOC vs 50% HBOC +TXA: 5.55% vs 5.65%, p=0.92). Additionally, the increased fibrinolysis seen with NS was reversed when TXA was present (WB vs 50% NS: 1.8% vs 1.65%, p=1.0).
Conclusion: HBOCs enhance fibrinolysis without the addition of tPA; moreover, this is independent of plasmin as the phenomenon persists in the presence of TXA. Our findings implicate the hemoglobin molecule or its components in stimulating fibrinolysis
