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Abstract
Blood substitutes, especially red blood cell (RBC) substitutes, have been developed for the past five decades and have several advantages over allogenic packed RBCs, including a prolonged half-life, lack of a cross-matching requirement, and minimal infection risk or concerns about immunologic reactions. There are two main groups in RBC substitutes: perfluorochemicals and hemoglobin-based oxygen carriers (HBOCs). HBOCs are made of hemoglobins from: human, bovine or recombinant and undergo three modification types: chemical (intramolecular cross-linking, polymerization, conjugation to macromolecules and combination of several chemical modifications), genetic, or technological (microencapsulation). The types, side effects, current status of clinical trials, and the future of HBOCs are described in details.
References
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Table 1.
Artificial O2 carriers (9)
Table 2.
Physico-chemical characteristics of modified hemoglobin solutions
| Source of Hb | Intramolecular modification | Intermolecular cross-linking | Concentrattion (g/dL) | Met.Hb (%) | Viscosity (cP) | COP (mm Hg) | P50 (mm Hg) | T1/2 (h) | Non polymerized (%) | Clinical Develop. Phase | |
|---|---|---|---|---|---|---|---|---|---|---|---|
| DCLHb | ODB | diaspirin | none | 10 | < 5.0 | 1.3 | 42 | 32 | 24 | > 99 | stopped |
| rHb1.1 | Hum. rec. | glycine | none | 5∼10 | 1.9 | 42 | 33 | 2 | na | stopped | |
| rHb2.0 | Hum. rec. | fusion of α-chains* | PEG-based* | 10 | 2.4 | 68 | 31 | na | stopped | ||
| HBOC-201 | bovine | glutaraldehyde | 13? | < 5.0 | 1.3 | 17 | 32∼3 | 8 24 | < 5 | III finished | |
| PolyHeme® | ODB | pyridoxal phosphate | glutaraldehyde | 10 | < 8.0 | 26∼30 | 0 24 | 1 | III finished | ||
| HemolinkTM | ODB | o-raffinose | o-raffinose | 10 | < 15.0 | 34 | 20 | 30∼40 | stopped | ||
| MP4 | ODB | PEG conjugation | none | 4.2?.2 | <0.5 | 2.5?.0 | 55?0 | 10 | 24 | 100 | II / III |
Hb = hemoglobin, Met Hb = methemoglobin, COP = colloid oncotic pressure, P50 = 02 partial pressure associated with a 50% hemoglobin saturation, T1/2 = intravascular half life (maximal values listed), ODB = outdated donor blood, hum. rec.= human recombinant, PEG = polyethylene glycol, na = not applicable,
* no more precise information was available in June 2004 (6, 9, 85)
DCLHb = HemAssist® = diaspirin cross-linked hemoglobin (Baxter Healthcare Corp., Deerfield, IL)
rHb1.1 = human recombinant hemoglobin version 1.1 (Somatogen Inc., Boulder, CO, later Baxter Healthcare Corp.)
rHb2.0 = human recombinant hemoglobin version 2.0 (Baxter Healthcare Corp.)
HBOC-201= Hemopure® = polymerized bovine hemoglobin (Biopure Corp., Cambridge, MA)
PolyHeme® = human polymerized hemoglobin (Northfield Laboratories Inc., Evanston, IL)
Hemolink® = hemoglobin raffimer (Hemosol Inc., Toronto, Ontario, Canada)
MP4 = Hemospan® = Maleimide-activated polyethylene glycol-modified hemoglobin (Sangart Inc., San Diego, CA)
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