Current Status and Future of Artificial Blood: Focusing on Red Blood Cell Substitutes

Jong-Hoon Kim; Ki-Young Lee

doi:10.5124/jkma.2009.52.2.168

J Korean Med Assoc > Volume 52(2); 2009 > Article

Kim and Lee: Current Status and Future of Artificial Blood - Focusing on Red Blood Cell Substitutes

Continuing Education Column

J Korean Med Assoc 2009; 52(2): 168-181.

Published online: January 10, 2009

DOI: http://dx.doi.org/10.5124/jkma.2009.52.2.168

Current Status and Future of Artificial Blood - Focusing on Red Blood Cell Substitutes

Jong-Hoon Kim, MD, Ki-Young Lee, MD

Department of Anesthesiology and Pain Medicine, and Anesthesia and Pain Research Institute, Yonsei University College of Medicine E - mail: kylee504@yuhs.ac

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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.

Key words: Blood substitute; Red blood cell substitute; Hemoglobin based oxygen carrier

Table 1.

Artificial O₂ carriers (9)

Hemoglobin based O₂ carriers

• Diaspirin cross-linked hemoglobin (DCLHb, HemAssist^®)

• Human recombinant hemoglobin version 1.1 (rHb1.1)

• Human recombinant hemoglobin version 2.0 (rHb2.0)

• Polymerized bovine hemoglobin (HBOC-201, Hemopure^®)

• Human polymerized hemoglobin (PolyHeme^®)

• Hemoglobin raffimer (Hemolink^??)

• Maleimide-activated polyethylene glycol-modified hemoglobin (MP4, Hemospan^®)

• Enzyme cross-linked polyhemoglobin

Perfluorocarbon emulsions

Perflubron emulsion (Oxygent^TM)

Nano-dimension artificial red blood cells

Allosteric modifier (RSR13)

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
Hemolink^TM	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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