Editorial: Blood substitutes better than blood?

Intaglietta, Marcos

doi:10.1111/j.1778-428x.2008.00092.x

Cited by 2 publications

(2 citation statements)

References 11 publications

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“…Despite these advantages, significant efforts at developing HBOCs and rHBOCs have not yet resulted in therapeutic licensure in the United States, although HBOC 201 (HemopureÔ; OPK Biotech, Boston, MA) is approved for human use in South Africa and Russia (40,72). The lack of approval of these HBOC products in the United States is primarily due to reports of adverse cardiovascular and cerebrovascular events associated with hypertension (4,18,26,40,44,55,64,65,72,74,81,88,94,105,138,143). In the case of recombinant HBOCs, additional barriers to development include globin denaturation, misfolding, and heme-orientational disorder, issues that arise during expression of recombinant heme proteins (46,108).…”

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confidence: 99%

Development of Recombinant Hemoglobin-Based Oxygen Carriers

Varnado

Mollan

Birukou

et al. 2013

Antioxidants & Redox Signaling

102

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Significance: The worldwide blood shortage has generated a significant demand for alternatives to whole blood and packed red blood cells for use in transfusion therapy. One such alternative involves the use of acellular recombinant hemoglobin (Hb) as an oxygen carrier. Recent Advances: Large amounts of recombinant human Hb can be expressed and purified from transgenic Escherichia coli. The physiological suitability of this material can be enhanced using protein-engineering strategies to address specific efficacy and toxicity issues. Mutagenesis of Hb can (i) adjust dioxygen affinity over a 100-fold range, (ii) reduce nitric oxide (NO) scavenging over 30-fold without compromising dioxygen binding, (iii) slow the rate of autooxidation, (iv) slow the rate of hemin loss, (v) impede subunit dissociation, and (vi) diminish irreversible subunit denaturation. Recombinant Hb production is potentially unlimited and readily subjected to current good manufacturing practices, but may be restricted by cost. Acellular Hb-based O 2 carriers have superior shelf-life compared to red blood cells, are universally compatible, and provide an alternative for patients for whom no other alternative blood products are available or acceptable. Critical Issues: Remaining objectives include increasing Hb stability, mitigating iron-catalyzed and iron-centered oxidative reactivity, lowering the rate of hemin loss, and lowering the costs of expression and purification. Although many mutations and chemical modifications have been proposed to address these issues, the precise ensemble of mutations has not yet been identified. Future Directions: Future studies are aimed at selecting various combinations of mutations that can reduce NO scavenging, autooxidation, oxidative degradation, and denaturation without compromising O 2 delivery, and then investigating their suitability and safety in vivo. Antioxid. Redox Signal. 18, 2314-2328.

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confidence: 99%

Development of Recombinant Hemoglobin-Based Oxygen Carriers

Varnado

Mollan

Birukou

et al. 2013

Antioxidants & Redox Signaling

102

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“…It is not obvious that an optimal plasma expander has already been devised; and blood is probably not optimal in this context. Moreover, the design of a blood substitute that has the properties of native blood in the circulation may be unattainable, particularly because it is not possible to reproduce the biomechanical characteristics of blood (Intaglietta, 2008). The pro-inflammatory effects of artificial blood substitutes are an area of concern, although some of the early work with PolyHeme and levels of Interleukins (IL-6 and IL-8), seemed to suggest a possible attenuation of this response in early trauma resuscitation (Moore et al, 2005).…”

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confidence: 99%

Fluids as oxygen carriers and the potential role in trauma resuscitation

Shirley

2008

Trauma

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Patients with major trauma present a challenge, often using large quantities of banked blood both at the time of injury and during their hospital stay. Blood transfusion is not without risk and is associated with high costs; it is immunosuppressive, rendering patients more susceptible to infection. In the western world, banked blood is fully screened and relatively safe; the same is not true in parts of the developing world, where high rates of HIV carriage make blood transfusion a risky undertaking. Additionally, blood transfusion as a vector for transmission of illnesses such as prion disease is a distinct possibility, for both the developed and developing world alike. The introduction of artificial blood substitutes would ameliorate some risk and also remove the cost of extensive blood testing. For trauma outside hospital, blood substitutes could compete directly with fluid resuscitation as donated blood is not usually available. Patients with prolonged transport times would appear to be the most obvious beneficiaries and volume expansion, along with improvement in oxygen-carrying capacity would be the ultimate goal. All clinicians confronted with the need for transfusion of homologous blood would welcome the development of a safe and reliable alternative to red blood cells in order to ensure oxygen transport to the tissues. However, even though research on red cell substitutes started more than 100 years ago, even now none of the heavily investigated compounds based on haemoglobin or perfluorocarbons has been released in Europe or the USA for routine clinical use.

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Editorial: Blood substitutes better than blood?

Cited by 2 publications

References 11 publications

Development of Recombinant Hemoglobin-Based Oxygen Carriers

Development of Recombinant Hemoglobin-Based Oxygen Carriers

Fluids as oxygen carriers and the potential role in trauma resuscitation

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