What are haemoglobin-based substitutes?
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Haemoglobin (Hb) is the molecule that gives red blood cells their characteristic red colour. It is defined as a 'respiratory pigment'. The red pigmentation arises from the four iron atoms it contains binding to oxygen in the lungs, which they subsequently release as they pass through the body's tissues. |
Hb-based substitutes currently under development use chemically modified haemoglobin. Such modifications are required since, if allowed to exist in the blood stream outside of the red blood cells, Hb causes problems. The two main problems associated with this 'cell free' Hb are:
| 1. Poor oxygen delivery to tissues - | As Hb behaves differently outside of red blood cells where enzymes and other substances control its oxygen binding and other characteristics. In many cases Hb has been shown to cause increases in patient blood pressure and constriction of blood vessels - this reduces oxygen delivery. |
| 2. Kidney damage - |
When existing freely in the bloodstream, Hb tends to rapidly break up into its components, which can damage the kidneys.
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Combating the problems of cell free haemoglobin
To improve the oxygen delivery of Hb and its stability in the bloodstream, so that it can act more effectively as a blood substitute, scientists have used a number of strategies for chemically-modifying the molecule. There are four main options for modifying Hb:
- Conjugation
- Cross-linking
- Polymerisation
- Encapsulation
The scientific background behind these modifications can be found at the 'Want to know more?' link above.
Where does the haemoglobin for substitutes come from?
There has been some concern over finding a suitable, cheap, plentiful and safe source of Hb, which can undergo any of the four chemical modifications to produce an effective blood substitute.
To-date there are
four potential sources of Hb:
| Haemoglobin source | Explanation | Advantages | Disadvantages |
| Human Blood | Involves extraction of Hb from outdated waste donor blood | Makes a resource from discarded, waste blood, therefore it is a cheap resource | Waste blood is diminishing as donor numbers fall and our handling/storage of donated blood improves. |
| Cow Blood | Uses Hb from cow slaughterhouse blood | Cheap, plentiful resource. Reduced need for the chemical modifications required with human Hb. | Unknown long-term effects on human immune system with repeat infusions. Concerns over disease transmission from UK cows infected with BSE |
| Micro-organisms | Genetically modified bacteria, fungi and even some plants can be made to produce Hb | Infinite supply. Avoids use of human or animal blood, thus avoiding cultural/ethical objections by certain religous groups. Potentially a source of pure Hb, free of virus and other blood components | Potentially high costs associated with large-scale production |
| Transgenic Animals | Genes responsible for human Hb production introduced into developing animal eggs. Animal then able to produce Hb when it matures | Potential infinite supply of large volumes of Hb | Potential ethical objections to using animals as 'Hb factories'. Possible processing difficulties with Hb extraction |