Hemoglobin-based oxygen carriers
Haemoglobin-based oxygen carriers are one of two main types of oxygen-carrying blood substitutes in development, the other one being perfluorocarbon emulsions (such as Fluosol). As of 2011 there are no haemoglobin-based oxygen carriers or perfluorocarbon emulsions approved for commercial use in North America or Europe. The only countries where these products are approved for general use is South Africa and Russia.
This is because they significantly increase the risk of death and myocardial infarction. It has been recommended that further phase III trials not be conducted until these products are as effective as the current standard of care.
Optimism about near term approval of oxygen carriers has decreased recently due to poor result from a number of clinical trials.
The development of a "perfect" blood substitute has been going on for many years. It is hoped that such a product would have certain advantages over human red cells, including rapid and widespread availability, fewer requirements with regard to storage, transport, and compatibility testing, a longer shelf life, and a more consistent supply. An ideal substitute would be less antigenic than allogenic red cells, and would have less risk of disease transmission.
Two main types of blood substitutes are in development: haemoglobin-based oxygen carrier (HBOCs) and perfluorocarbon emulsions.
The general task of blood within the frame of classic transfusion medicine is oxygen tissue supply (oxygen transport from lung to tissue, oxygen release and picking up carbon dioxide). All of this is accomplished with haemoglobin (Hb), the oxygen carrier protein contained within red cells. According to this simplified postulation, early attempts to develop blood substitutes was focused on simple cell-free solution of haemoglobin.
Haemoglobin is a tetramer of two a and two b polypeptide chains, each of which is bound to an iron-containing heme group which each bind one oxygen molecule. This oxygen heme bond results in a conformational change in haemoglobin molecule, which progressively increases the affinity of haemoglobin for additional oxygen molecules. The main consequence is that the small change in oxygen partial pressure results in a large change in the amount of oxygen bound or released by the haemoglobin. This is widely known as oxygen–haemoglobin dissociation curves. Under conditions of increased pH or decreased temperature or 2,3–diphosphoglycerate (2,3-DPG, product of RBC glycolytic pathway) oxygen-haemoglobin dissociation curve is shifted to the left resulting in an increased affinity of haemoglobin for oxygen. In contrast, by decreased pH increased of temperature or an increase of 2,3-DPG-concentration curve is shifted to the right allowing the release of oxygen to tissue at higher than normal oxygen partial pressure. According to modern trends this ability today could be termed the "intelligent natural nanotechnique product". However, it is of great importance that cell free haemoglobin maintains its ability to transport oxygen outside of the RBC. Stroma-free haemoglobin has been investigated as an oxygen carrier since the 1940s, when researchers realized that native haemoglobin is not antigenic. The ability to transport oxygen outside of the RBC and that application of haemoglobin solution did not require compatibility testing and allowed sterilisation promote isolated Hb as a substitute for red cells.
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