The Effect of Sepsis on the Erythrocyte

Abstract

Sepsis induces a wide range of effects on the red blood cell (RBC). Some of the effects including altered metabolism and decreased 2,3-bisphosphoglycerate are preventable with appropriate treatment, whereas others, including decreased erythrocyte deformability and redistribution of membrane phospholipids, appear to be permanent, and factors in RBC clearance. Here, we review the effects of sepsis on the erythrocyte, including changes in RBC volume, metabolism and hemoglobin’s affinity for oxygen, morphology, RBC deformability (an early indicator of sepsis), antioxidant status, intracellular Ca2+ homeostasis, membrane proteins, membrane phospholipid redistribution, clearance and RBC O2-dependent adenosine triphosphate efflux (an RBC hypoxia signaling mechanism involved in microvascular autoregulation). We also consider the causes of these effects by host mediated oxidant stress and bacterial virulence factors. Additionally, we consider the altered erythrocyte microenvironment due to sepsis induced microvascular dysregulation and speculate on the possible effects of RBC autoxidation. In future, a better understanding of the mechanisms involved in sepsis induced erythrocyte pathophysiology and clearance may guide improved sepsis treatments. Evidence that small molecule antioxidants protect the erythrocyte from loss of deformability, and more importantly improve septic patient outcome suggest further research in this area is warranted. While not generally considered a critical factor in sepsis, erythrocytes (and especially a smaller subpopulation) appear to be highly susceptible to sepsis induced injury, provide an early warning signal of sepsis and are a factor in the microvascular dysfunction that has been associated with organ dysfunction.

Bacterial neuraminidase‐mediated erythrocyte desialylation provokes cell surface aminophospholipid exposure

“…15,34,37 Mounting evidence suggests that increased PS externalization, triggered by a host of bacterial components such as peptidoglycan, lipopeptides, sphingomyelinase, Pseudomonas aeruginosa pyocyanin, and α-hemolysin, shortens erythrocyte lifespan, thus, contributing to sepsis-associated anemia. 17,20,22,29,38 Along these lines, it may be conjectured that enhanced neuraminidase activity in septic patients contributes to aggravated eryptosis and anemia. Further insights on the putative biological implications of neuraminidase-induced erythrocyte desialylation may be garnered from previous studies on animal models of parasitic infections.…”

“…15,16 Escalated neuraminidase activity and increased plasma SA levels are associated with altered erythrocyte function in sepsis. 15,17 Artificial depletion of SA by neuraminidase treatment and subsequent autologous transfusion of erythrocytes in animal models was reported to result in their rapid clearance from the circulation by the mononuclear phagocyte system. 18 Accordingly, excessive loss of circulating desialylated erythrocytes has been directly linked to the pathogenesis of anemia.…”

A New Look at the Structures of Old Sepsis Actors by Exploratory Data Analysis Tools

“…Hemoglobin usually drops in septic patients, due to a large number of factors, most of them still now undefined. The concentration of Hb in blood samples is currently accepted as a potent prognostic marker [39][40][41][42][43]. It is one of the first proteins whose structure was resolved by X-ray crystallography since the 1960s [44].…”

The Clinical Value of Red Blood Cell Distribution Width as a Prognosis Factor and Severity Marker in Sepsis and Septic Shock

“…Red blood cells rheological changes can alter RDW in septic patients [13]. Mechanisms of changes in shape (sphericity), volume and deformability are still not completely understood [13], but several have been proposed in septic patients: phosphatidylserine redistribution on the outer red blood cell membrane leaflet [14,15], alterations of RBC sialic acid membrane content [16,17], band 3 protein phosphorylation [18], redox imbalances [19][20][21], calcium [22], 2,3-diphosphoglycerate [23] and adenosine triphosphate [24] homeostasis alterations and nitric oxide pathway modulation [25,26]. Also, inflammatory response indirectly modulates hematopoiesis through abnomal iron metabolism, increased hemolysis and decreased erythrocyte life span which will lead, in turn, to an increased release of the immature forms into the bloodstream [19].…”