Oxygen Therapeutics: Pursuit of an Alternative to the Donor Red Blood Cell

2007 ◽  
Vol 131 (5) ◽  
pp. 734-741
Author(s):  
Paul M. Ness ◽  
Melissa M. Cushing
Keyword(s):  
Blood Donation ◽  
Blood Substitute ◽  
Blood Substitutes ◽  
Red Cells ◽  
Phase Iii ◽  
Red Cell ◽  
Oxygen Carriers ◽  
Term Survival ◽  
Phase Iii Clinical Trials ◽  
Human Red Blood Cells

Abstract Context.—There is no true substitute for the many functions of human red blood cells, and synthetic products will not replace the need for blood donation in the foreseeable future. Hemoglobin-based oxygen carriers have many characteristics that would serve as a useful adjunct to red cells in clinical settings. Over time, these technologies have the potential to dramatically reshape the practice of transfusion medicine. Objective.—To review the characteristics and potential utility of hemoglobin-based oxygen carriers and perfluorocarbon-based oxygen carriers. Several hemoglobin-based oxygen carriers are under study in phase III clinical trials. Novel uses for synthetic oxygen therapeutics are emphasized. Data Sources.—All published reports with the key words oxygen therapeutics, blood substitutes, and red cell substitutes from 1933 until March 2006 were searched through Medline. Significant findings were synthesized. Conclusions.—Recognition of the true impact of red cell substitutes is still several years away. The most compelling products, hemoglobin-based oxygen carriers, have potential use in trauma, providing immediate oxygen-carrying support in the face of alloantibodies or autoantibodies, and in other clinical situations in which long-term survival of red cells is not essential. In the interim, efforts should be focused on enhancing the current blood supply system while supporting ongoing and planned blood substitute research efforts, including trials assessing novel clinical indications for these products.

scholarly journals Kinetics and stoichiometry of Na-dependent Li transport in human red blood cells.

1978 ◽  
Vol 72 (2) ◽  
pp. 249-265 ◽  
Author(s):  
B Sarkadi ◽  
J K Alifimoff ◽  
R B Gunn ◽  
D C Tosteson
Keyword(s):  
Transport System ◽  
Red Cells ◽  
Normal Male ◽  
Red Cell ◽  
Red Cell Membrane ◽  
Human Red Blood Cells ◽  
Na Efflux ◽  
Tightly Coupled ◽  
Male Subjects ◽  
Human Red Cells

This paper describes the kinetics and stoichiometry of a tightly coupled Na-Li exchange transport system in human red cells. The system is inhibited by phloretin and furosemide but not by ouabain. Li influx by this system increases and saturates with increasing concentrations of external Li and internal Na and is inhibited competitively by external Na. Comparable functions relate Li efflux and Na efflux to internal and external Li and Na concentrations. Analysis of these relations yields the following values for the ion concentrations required to half-maximally activate the transport system: internal Na and Li 9.0 and 0.5 mM, respectively, external Na and Li 25 and 1.5 mM, respectively. The system performs a 1:1 exchange of Na and Li moving in opposite directions across the red cell membrane. We found no evidence for a simultaneous transport of more than one Na and Li by the system. The maximum transport rate of Na-dependent Li transport varied between 0.1 and 0.37 mmol/(liter of cells X h) in the red cells of the five normal male subjects studied. No significant variations between individual subjects were observed for bicarbonate-stimulated Li transport and for the residual Li fluxes which occur in the absence of bicarbonate and in the presence of ouabain plus phloretin.

scholarly journals How Do Red Blood Cells Die?

2021 ◽  
Vol 12 ◽  
Author(s):  
Perumal Thiagarajan ◽  
Charles J. Parker ◽  
Josef T. Prchal
Keyword(s):  
Red Blood Cells ◽  
Blood Cells ◽  
Red Cells ◽  
Cell Labeling ◽  
Red Cell ◽  
Average Life Span ◽  
Human Red Blood Cells ◽  
Physicochemical Changes ◽  
Cell Clearance

Normal human red blood cells have an average life span of about 120 days in the circulation after which they are engulfed by macrophages. This is an extremely efficient process as macrophages phagocytose about 5 million erythrocytes every second without any significant release of hemoglobin in the circulation. Despite large number of investigations, the precise molecular mechanism by which macrophages recognize senescent red blood cells for clearance remains elusive. Red cells undergo several physicochemical changes as they age in the circulation. Several of these changes have been proposed as a recognition tag for macrophages. Most prevalent hypotheses for red cell clearance mechanism(s) are expression of neoantigens on red cell surface, exposure phosphatidylserine and decreased deformability. While there is some correlation between these changes with aging their causal role for red cell clearance has not been established. Despite plethora of investigations, we still have incomplete understanding of the molecular details of red cell clearance. In this review, we have reviewed the recent data on clearance of senescent red cells. We anticipate recent progresses in in vivo red cell labeling and the explosion of modern proteomic techniques will, in near future, facilitate our understanding of red cell senescence and their destruction.

scholarly journals Red blood cell size is important for adherence of blood platelets to artery subendothelium

Blood ◽  
1983 ◽  
Vol 62 (1) ◽  
pp. 214-217 ◽  
Author(s):  
PA Aarts ◽  
PA Bolhuis ◽  
KS Sakariassen ◽  
RM Heethaar ◽  
JJ Sixma
Keyword(s):  
Red Blood Cells ◽  
Cell Size ◽  
Blood Cells ◽  
Blood Platelets ◽  
Red Cells ◽  
Cell Diameter ◽  
Red Cell ◽  
Human Red Blood Cells ◽  
Platelet Adherence ◽  
Order Of Magnitude

Abstract The hematocrit is one of the main factors influencing platelet adherence to the vessel wall. Raising the hematocrit causes an increase of platelet accumulation of about an order of magnitude. Our studies concern the role of red cell size. We have studied this effect using an annular perfusion chamber, according to Baumgartner, with human umbilical arteries and a steady-flow system. Normal human red blood cells (MCV 95 cu mu) increased platelet adherence sevenfold, as the hematocrit increases from 0 to 0.6. Small erythrocytes from goats (MCV 25 cu mu) caused no increment in adherence in the same hematocrit range. Rabbit erythrocytes (MCV 70 cu mu) caused an intermediate increase in adherence. Red blood cells from newborns (MCV 110–130 cu mu) caused a larger increase in platelet adherence than normal red cells at hematocrit 0.4. These results were further confirmed with large red blood cells from two patients. Experiments with small red cells (MCV 70 cu mu) of patients with iron deficiency showed that platelet adherence was similar to normal red cells, provided the red cell diameter was normal. Small red blood cells of a patient with sideroblastic anemia caused decreased adherence. These data indicate that red cell size is of major importance for platelet adherence. Red cell diameter is more important than average volume. However, for size differences in the human range, the hematocrit remains the dominant parameter.

scholarly journals A REVIEW ON ARTIFICIAL BLOOD: A SOURCE WE NEED

2017 ◽  
Vol 10 (9) ◽  
pp. 38 ◽  
Author(s):  
Krishna Veni R ◽  
Brindha Devi P ◽  
Ivo Romauld S
Keyword(s):  
Human Blood ◽  
Oxygen Carrier ◽  
Blood Substitute ◽  
Blood Substitutes ◽  
Blood Collection ◽  
Oxygen Carriers ◽  
Blood Products ◽  
Artificial Blood ◽  
Normal Human ◽  
Normal Human Blood

Blood is a liquid tissue, in which abundant chemical factors and millions of different cells are dissolved. It is one of the most demanding sources in clinical and medical aspects. The issues and cost of human blood collection and storage directed this procedure toward the use of alternative blood. Thus, came an invention of artificial blood and blood substitutes. These alternative blood or blood substitute is a substance which is made to play as a substitute of erythrocytes. Thus, the main objective is to replace the normal human blood with artificial blood substitutes in the place of blood transfusion during surgeries and organ transfusion. Two major and focused blood substitutes in pharmaceutical aspects are perfluorocarbons and hemoglobin-based oxygen carriers (HBOC’s). Among these HBOCs vaguely resemble normal human blood. These blood substitutes are to allow flow through the blood stream to carry the oxygen and supply it to heart and other parts of the blood. They are used to fill the lost fluid volume. They are also called as plastic blood with iron atom as the base. They are found to serve as a good oxygen carrier. The results showed by these products are discussed, and they proved that they can act as a blood substitute and also they can reach the human tissue easier than erythrocytes and can control oxygen directly. However, these artificial blood products are being processed in research laboratories for good outcome. Their important functions are oxygen carrying capacity and to replace the lost blood volume in the human body. Their special features are survivability over a wider range of temperatures, eliminating cross matching, cost efficient, pathogen free, long shelf life, minimal side effects. Thus, artificial blood products are really a good alternative source which we need for replacing normal human blood.

scholarly journals Red blood cell size is important for adherence of blood platelets to artery subendothelium

Blood ◽  
1983 ◽  
Vol 62 (1) ◽  
pp. 214-217 ◽  
Author(s):  
PA Aarts ◽  
PA Bolhuis ◽  
KS Sakariassen ◽  
RM Heethaar ◽  
JJ Sixma
Keyword(s):  
Red Blood Cells ◽  
Cell Size ◽  
Blood Cells ◽  
Blood Platelets ◽  
Red Cells ◽  
Cell Diameter ◽  
Red Cell ◽  
Human Red Blood Cells ◽  
Platelet Adherence ◽  
Order Of Magnitude

The hematocrit is one of the main factors influencing platelet adherence to the vessel wall. Raising the hematocrit causes an increase of platelet accumulation of about an order of magnitude. Our studies concern the role of red cell size. We have studied this effect using an annular perfusion chamber, according to Baumgartner, with human umbilical arteries and a steady-flow system. Normal human red blood cells (MCV 95 cu mu) increased platelet adherence sevenfold, as the hematocrit increases from 0 to 0.6. Small erythrocytes from goats (MCV 25 cu mu) caused no increment in adherence in the same hematocrit range. Rabbit erythrocytes (MCV 70 cu mu) caused an intermediate increase in adherence. Red blood cells from newborns (MCV 110–130 cu mu) caused a larger increase in platelet adherence than normal red cells at hematocrit 0.4. These results were further confirmed with large red blood cells from two patients. Experiments with small red cells (MCV 70 cu mu) of patients with iron deficiency showed that platelet adherence was similar to normal red cells, provided the red cell diameter was normal. Small red blood cells of a patient with sideroblastic anemia caused decreased adherence. These data indicate that red cell size is of major importance for platelet adherence. Red cell diameter is more important than average volume. However, for size differences in the human range, the hematocrit remains the dominant parameter.

scholarly journals Plasma-mediated alterations of erythrocyte deformability by perfluorochemical blood substitutes

Blood ◽  
1986 ◽  
Vol 67 (1) ◽  
pp. 173-176 ◽  
Author(s):  
GM Holloway ◽  
EA O'Rear ◽  
BM Fung
Keyword(s):  
Volumetric Flow Rate ◽  
Erythrocyte Deformability ◽  
Blood Substitutes ◽  
Red Cells ◽  
Red Cell ◽  
Cell Deformability ◽  
Red Cell Deformability ◽  
Filtration Method ◽  
Mean Cell Volume

Abstract The effect of perfluorochemical blood substitutes (eg, Oxypherol or Fluosol-DA) on red cell deformability was investigated because these emulsions are in direct contact with red cells when they are used as temporary circulatory aids. Erythrocyte deformability was assessed by a constant volumetric flow rate filtration method. The results of in vitro incubation experiments indicate that perfluorotributylamine causes the deformability of human red cells to decrease significantly in the presence of plasma. However, there is no obvious loss in the deformability when washed cells are used. Neither mean cell volume nor white cells appear to be responsible for the observed effects of perfluorotributylamine. Perfluorodecalin and perfluorotripropylamine, two perfluorochemical compounds that are widely applied clinically, do not induce significant changes in red cell deformability with or without plasma. These results indicate the need for in vitro testing in the development of perfluorochemicals as blood substitutes.

scholarly journals Plasma-mediated alterations of erythrocyte deformability by perfluorochemical blood substitutes

Blood ◽  
1986 ◽  
Vol 67 (1) ◽  
pp. 173-176
Author(s):  
GM Holloway ◽  
EA O'Rear ◽  
BM Fung
Keyword(s):  
Volumetric Flow Rate ◽  
Erythrocyte Deformability ◽  
Blood Substitutes ◽  
Red Cells ◽  
Red Cell ◽  
Cell Deformability ◽  
Red Cell Deformability ◽  
Filtration Method ◽  
Mean Cell Volume

The effect of perfluorochemical blood substitutes (eg, Oxypherol or Fluosol-DA) on red cell deformability was investigated because these emulsions are in direct contact with red cells when they are used as temporary circulatory aids. Erythrocyte deformability was assessed by a constant volumetric flow rate filtration method. The results of in vitro incubation experiments indicate that perfluorotributylamine causes the deformability of human red cells to decrease significantly in the presence of plasma. However, there is no obvious loss in the deformability when washed cells are used. Neither mean cell volume nor white cells appear to be responsible for the observed effects of perfluorotributylamine. Perfluorodecalin and perfluorotripropylamine, two perfluorochemical compounds that are widely applied clinically, do not induce significant changes in red cell deformability with or without plasma. These results indicate the need for in vitro testing in the development of perfluorochemicals as blood substitutes.

scholarly journals Re-evaluation of the structural integrity of red-cell glycoproteins during aging in vivo and nutrient deprivation

1987 ◽  
Vol 242 (1) ◽  
pp. 115-121 ◽  
Author(s):  
A Brovelli ◽  
C Seppi ◽  
A Bardoni ◽  
C Balduini ◽  
H U Lutz
Keyword(s):  
Blood Cells ◽  
Structural Integrity ◽  
Elevated Temperatures ◽  
White Cell ◽  
Red Cells ◽  
Glycophorin A ◽  
Red Cell ◽  
Density Separation ◽  
Human Red Blood Cells

Results presented in this paper show that removal of white-cell contaminations from human red blood cells by filtration through cellulose [Beutler, West & Blume (1976) J. Lab. Clin. Med. 88, 328-333] is a necessity whenever red cells are incubated at elevated temperatures or haemolysed after density separation. Omission of this precaution results in proteolysis of sialoglycoproteins in membranes from less-dense (young), but not dense (old), subpopulations. This proteolytic damage occurs during haemolysis of the cytoplasmic domain of glycophorin. A different type of proteolysis occurs if white-cell-contaminated red cells are incubated in the absence of glucose at elevated temperatures. Red cells release sialoglycopeptides. This process is stimulated by Ca2+ ions and is accompanied by the release of vesicles that differ from spectrin-free vesicles [Lutz, Liu & Palek (1977) J. Cell Biol. 73, 548-560]. This sialoglycopeptide release is dependent on white-cell contamination and is not required for the release of spectrin-free vesicles.

scholarly journals Artificial Blood: A Futuristic Dimension of Modern Day Transfusion Sciences

2019 ◽  
Vol 17 (1) ◽  
pp. 11-16 ◽  
Author(s):  
Rudrashish Haldar ◽  
Devendra Gupta ◽  
Shweta Chitranshi ◽  
Manish Kumar Singh ◽  
Sumit Sachan
Keyword(s):  
Blood Substitute ◽  
Blood Substitutes ◽  
The Body ◽  
Oxygen Carriers ◽  
Artificial Blood ◽  
Blood Haemoglobin ◽  
Available Technology ◽  
Donated Blood ◽  
Made In ◽  
The Ideal

Artificial blood is an innovative concept of transfusion medicine where specifically designed compounds perform the task of transport and delivery of oxygen in the body to replace this function of allogenic human blood transfusion. Several molecules have been developed in the past few decades to achieve this objective and continous refinements are being continuously made in the quest of the ideal blood substitute. Currently, available technology manufactures artificial blood from haemoglobin obtained from outdated human/bovine blood (Haemoglobin Based Oxygen Carriers) or utilizing Perfluorocarbons. These synthetic blood substitutes are advantageous in that they do not require compatibility testing, are free from blood borne infections, have prolonged shelf life and do not require refrigeration. Artificial blood is projected to have a significant impact on the development of medical care in the future. It can complement the current blood products for transfusion and create a stable supply of safe and effective products. It is likely to reduce the requirements of blood transfusions drastically especially in settings of trauma and surgery thereby reducing the reliance on banked donated blood.

scholarly journals Osmotic Hemolysis of Chemically Modified Red Blood Cells

Blood ◽  
1969 ◽  
Vol 33 (2) ◽  
pp. 170-178 ◽  
Author(s):  
RICHARD F. BAKER ◽  
NAOMI R. GILLIS
Keyword(s):  
Red Blood Cells ◽  
Blood Cells ◽  
Red Cells ◽  
Red Cell ◽  
Membrane Repair ◽  
Chemically Modified ◽  
Osmotic Hemolysis ◽  
Human Red Blood Cells ◽  
Single Membrane ◽  
Crown Formation

Abstract The mechanism of osmotic hemolysis of human red blood cells has been investigated after mild fixation in glutaraldehyde. A mass of precipitated hemoglobin (crown) is seen around a single membrane break which may be as large as 2µ in diameter. Ghosts with large holes are not seen and it is believed that membrane repair takes place. Hemoglobin extrusion by this mechanism takes place only around the rim of the red cell. Both old and young red cells exhibit crown formation, but old cells require longer fixation than do young cells. A correlation with previous work on mode of osmotic hemolysis of red cells is discussed.

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