Emerging Role of Hemoglobin Solutions in Trauma Care

Moore, Ernest E.

doi:10.1111/j.1778-428x.2005.tb00134.x

Cited by 2 publications

(3 citation statements)

References 82 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%

“…They are analogous to non-rHBOCs, which are constructed from human or animal Hb obtained from whole blood. Both types of products can be transfused in place of packed red blood cells to restore impaired oxygen transport and offer the following advantages: (i) universal compatibility; (ii) longer shelf-life; (iii) diminished risk of disease transmission; (iv) enhanced oxygen delivery; (v) improved rheological properties; (vi) improved uniformity in composition; (vii) more reliable availability; and (viii) use by individuals who cannot receive conventional blood transfusions for clinical, geographical, or religious reasons (55,88,94,143,147). 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).…”

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confidence: 99%

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Development of Recombinant Hemoglobin-Based Oxygen Carriers

Varnado

Mollan

Birukou

et al. 2013

Antioxidants & Redox Signaling

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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%

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Development of Recombinant Hemoglobin-Based Oxygen Carriers

Varnado

Mollan

Birukou

et al. 2013

Antioxidants & Redox Signaling

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“…The alternative oxygen carriers under active clinical testing are two polymerized hemoglobins [33,34]. They do carry sufficient oxygen to support life, but little is known about their toxicities.…”

Section: New Technology For Hemorrhage Treatmentmentioning

confidence: 99%