Hemorrhagic blood failure: Oxygen debt, coagulopathy, and endothelial damage

Nathan J White, Kevin R Ward, Shibani Pati, Geir Strandenes, Andrew P Cap, Nathan J White, Kevin R Ward, Shibani Pati, Geir Strandenes, Andrew P Cap

Abstract

Our understanding of the events taking place within the blood following severe injury with hemorrhagic shock is quickly evolving. Traditional concepts have given way to a detailed and nuanced understanding of coagulopathy, bleeding, and shock at the cellular and biochemical levels. In doing so, the tremendous complexity of events taking place within the blood have been illuminated and present an additional challenge. In this review, we seek to understand shock, endotheliopathy, and coagulopathy not as isolated events, but rather as the result of changes taking place within a single dynamic organ system. This review will highlight the key linkages existing between blood and endothelium and how these processes are perturbed by hemorrhagic shock to produce a syndrome that we call “hemorrhagic blood failure.” From this perspective, it may be regarded that the blood organ system fails in providing its vital functions predictably after injury. We review how accumulation of oxygen debt during shock leads to endotheliopathy and coagulopathy, and how current transfusion strategies may impact the syndrome of hemorrhagic blood failure.

Conflict of interest statement

Conflicts of Interest Statement: N.J.W holds intellectual property regarding detection methods for oxidative modifications of fibrinogen. K.R. Ward has a number of invention disclosures and patents pending for coagulation and oxidative stress monitoring technologies through the University of Michigan and no direct conflicts with the information contained in this manuscript. S. Pati, G. Strandenes, and A. Cap report no direct conflicts of interest with the information contained in this manuscript. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the US Department of the Army or the US Department of Defense.

Figures

Figure 1
Figure 1
Schematic representing the components of hemorrhagic blood failure.
Figure 2
Figure 2
Schematic of key linkages between oxygen debt, cellular dysfunction, and coagulopathy during hemorrhagic blood failure.
Figure 3
Figure 3
Schematic summarizing the effects of individual blood products on the three components of hemorrhagic blood failure. PRBC= packed red blood cells, Cryo= cryoprecipitate

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