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Biomolecules 2017, 7(1), 2; doi:10.3390/biom7010002

Hemoglobin-Based Blood Substitutes and the Treatment of Sickle Cell Disease: More Harm than Help?

Laboratory of Biochemistry and Vascular Biology, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD 20993, USA
Academic Editor: Jürg Bähler
Received: 16 November 2016 / Revised: 20 December 2016 / Accepted: 26 December 2016 / Published: 4 January 2017
View Full-Text   |   Download PDF [992 KB, uploaded 4 January 2017]   |  

Abstract

Intense efforts have been made by both industry and academia over the last three decades to produce viable hemoglobin (Hb)-based oxygen carriers (HBOCs), also known as “blood substitutes”. Human trials conducted so far by several manufactures in a variety of clinical indications, including trauma, and elective surgeries have failed and no product has gained the Food and Drug Administration approval for human use. Safety concerns due to frequent incidences of hemodynamic, cardiac events, and even death led to the termination of some of these trials. Several second generation HBOC products that have been chemically and/or genetically modified (or in some cases ligated with carbon monoxide (CO)) found a new clinical application in conditions as complex as sickle cell disease (SCD). By virtue of higher oxygen affinity (P50) (R-state), and smaller size, HBOCs may be able to reach the microvasculature unload of oxygen to reverse the cycles of sickling/unsickling of the deoxy-sickle cell Hb (HbS) (T-state), thus preventing vaso-occlusion, a central event in SCD pathophysiology. However, biochemically, it is thought that outside the red blood cell (due to frequent hemolysis), free HbS or infused HBOCs are capable of interfering with a number of oxidative and signaling pathways and may, thus, negate any benefit that HBOCs may provide. This review discusses the advantages and disadvantages of using HBOCs in SCD. View Full-Text
Keywords: hemoglobin; blood substitutes; sickle cell disease; heme oxidation hemoglobin; blood substitutes; sickle cell disease; heme oxidation
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Alayash, A.I. Hemoglobin-Based Blood Substitutes and the Treatment of Sickle Cell Disease: More Harm than Help? Biomolecules 2017, 7, 2.

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