Investigating the Relationship between Bleeding, Clotting, and Coagulopathy During Automated Partial REBOA Strategies in a Highly Lethal Porcine Hemorrhage Model

Abstract

Abstract Background Death due to hemorrhagic shock, particularly, non-compressible truncal hemorrhage (NCTH), remains one of the leading causes of potentially preventable deaths. Automated partial and intermittent resuscitative endovascular balloon occlusion of the aorta (i.e., pREBOA and iREBOA, respectively) are lifesaving endovascular strategies aimed to achieve quick hemostatic control while mitigating distal ischemia. In iREBOA, the balloon is titrated from full occlusion to no occlusion intermittently whereas in pREBOA, a partial occlusion is maintained. Therefore, these two interventions impose different hemodynamic conditions, which may impact coagulation and the endothelial glycocalyx layer (EGL). In this study, we aimed to characterize the clotting kinetics and coagulopathy associated with iREBOA and pREBOA, using thromboelastography (TEG). We hypothesized that iREBOA would be associated with a more hypercoagulopathic response compared to pREBOA due to more oscillatory flow. Methods Yorkshire swine (n = 8/group) were subjected to an uncontrolled hemorrhage by liver transection, followed by 90 minutes of automated partial REBOA (pREBOA), intermittent REBOA (iREBOA), or no balloon support (Control). Hemodynamic parameters were continuously recorded, and blood samples were serially collected during the experiment (i.e., 8 key time points: baseline (BL), T0, T10, T30, T60, T90, T120, T210 minutes). Citrated kaolin heparinase (CKH) assays were run on a TEG 5000 (Haemonetics, Niles, IL). General linear mixed models were employed to compare differences in TEG parameters between groups and over time using STATA (v17; College Station, TX), while adjusting for sex and weight. Results As expected, iREBOA was associated with more oscillations in proximal pressure (and greater magnitudes of peak pressure) because of the intermittent periods of full aortic occlusion and complete balloon deflation, compared to pREBOA. Despite these differences in acute hemodynamics, there were no significant differences in any of the TEG parameters between iREBOA and pREBOA groups. However, animals in both groups experienced a significant reduction in clotting times (R-time: p < 0.001; K-time: p < 0.001) and clot strength (MA: p = 0.01; G: p = 0.02) over the duration of the experiment. Conclusions Despite observing acute differences in peak proximal pressures between iREBOA and pREBOA groups, we did not observe any significant differences in TEG parameters between iREBOA and pREBOA. The changes in TEG profiles were significant over time, indicating that a severe hemorrhage followed by both pREBOA and iREBOA can result in faster clotting reaction times (i.e., R-times). Nevertheless, when considering the significant reduction in transfusion requirements and more stable hemodynamic response in the pREBOA group, there may be some evidence favoring pREBOA usage over iREBOA.