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. 2024 Feb 1;61(2):322-329.
doi: 10.1097/SHK.0000000000002299. Epub 2023 Dec 28.

RESUSCITATIVE ENDOVASCULAR BALLOON OCCLUSION OF THE AORTA: ZONE 1 REPERFUSION-INDUCED COAGULOPATHY

Alexis L Cralley  1 , Ernest E Moore, Ian LaCroix  2 , T J Schaid  1 , Otto Thielen  1 , William Hallas  1 , Patrick Hom  1 , Sanchayita Mitra  1 , Marguerite Kelher  3 , Kirk Hansen  2 , Mitchell Cohen  1 , Christopher Silliman, Angela Sauaia  4 , Charles J Fox  5
Affiliations

RESUSCITATIVE ENDOVASCULAR BALLOON OCCLUSION OF THE AORTA: ZONE 1 REPERFUSION-INDUCED COAGULOPATHY

Alexis L Cralley et al. Shock. .

Abstract

Objective: We sought to identify potential drivers behind resuscitative endovascular balloon occlusion of the aorta (REBOA) induced reperfusion coagulopathy using novel proteomic methods. Background: Coagulopathy associated with REBOA is poorly defined. The REBOA Zone 1 provokes hepatic and intestinal ischemia that may alter coagulation factor production and lead to molecular pathway alterations that compromises hemostasis. We hypothesized that REBOA Zone 1 would lead to reperfusion coagulopathy driven by mediators of fibrinolysis, loss of coagulation factors, and potential endothelial dysfunction. Methods: Yorkshire swine were subjected to a polytrauma injury (blast traumatic brain injury, tissue injury, and hemorrhagic shock). Pigs were randomized to observation only (controls, n = 6) or to 30 min of REBOA Zone 1 (n = 6) or REBOA Zone 3 (n = 4) as part of their resuscitation. Thromboelastography was used to detect coagulopathy. ELISA assays and mass spectrometry proteomics were used to measure plasma protein levels related to coagulation and systemic inflammation. Results: After the polytrauma phase, balloon deflation of REBOA Zone 1 was associated with significant hyperfibrinolysis (TEG results: REBOA Zone 1 35.50% versus control 9.5% vs. Zone 3 2.4%, P < 0.05). In the proteomics and ELISA results, REBOA Zone 1 was associated with significant decreases in coagulation factor XI and coagulation factor II, and significant elevations of active tissue plasminogen activator, plasmin-antiplasmin complex complexes, and syndecan-1 (P < 0.05). Conclusion: REBOA Zone 1 alters circulating mediators of clot formation, clot lysis, and increases plasma levels of known markers of endotheliopathy, leading to a reperfusion-induced coagulopathy compared with REBOA Zone 3 and no REBOA.

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Conflict of interest statement

EEM has patents pending related to coagulation and fibrinolysis diagnostics and therapeutic fibrinolytics and was a cofounder of ThromboTherepeutics. EEM has received grant support from Haemonetics, Hemosonics, Werfen, Stago, and Prytime outside the submitted work. CJF is a clinical consultant for Prytime Medical. The remaining authors report no conflict of interests.

Figures

Figure 1.
Figure 1.. Global Proteomic Changes Depended Upon Intervention.
Normalization and statistical analyses were performed using MetaboAnalyst software. A) Partial least squares – discriminant analysis (PLS-DA) of swine proteomes across the monitored time course showed distinct clustering dependent on the intervention. The highest separation was observed on component 2 (15.4%) which was driven by the Zone 1 REBOA intervention. B) Heat map of the top 50 proteins that were significantly different between interventions as measured by ANOVA. Protein intensities were normalized and exhibited on a scale from −4 (blue) to 4 (red). Time points were ordered from left to right per swine for each intervention. Proteins were hierarchically clustered to show groups with similar intensities.
Figure 2.
Figure 2.. Changes in Thrombin (ELISA) and FII (Mass Spectrometry).
Mean Thrombin concentrations determined by ELISA plotted with standard deviation. Proteomic levels of Factor II (reflecting both prothrombin and thrombin) are graphed as mean change from baseline plotted with standard deviation. Plotted p-values represent significant differences of Zone 1 REBOA group at that time compared to baseline.
Figure 3.
Figure 3.. Changes in the concentrations of tPA, PAP, tPA-PAI complex, and plasminogen from ELISA results.
Mean ELISA concentrations are plotted with standard deviations.
See this image and copyright information in PMC

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