“Donate blood to save lives” is a popular poster commonly seen in front of hospitals. Furthermore, a sorry state of affairs at blood banks, raises the alarm for something that can work as a replacement for natural human blood. Yes, Blood Substitute (BS) is the answer. BS is an infusible fluid that eliminates the need for crossmatching and refrigeration, has a long shelf life, reduces the risk of iatrogenic infection and would provide a potentially lifesaving option for severe hemorrhage, chronic symptomatic anemia and surgical patients especially in rural areas and military settings. People have been searching for blood substitutes since 1616, when William Harvey discovered how blood circulates in the body. An artificial blood would relieve shortages and prevent patients being infected by contaminated supplies. Ideally, it could be given to anyone to restore life when blood supply is limited.
Modified hemoglobin and perfluorochemicals are the two major groups of BS. Hemoglobin is the major metalloprotein of red blood cells (RBC) responsible for transporting oxygen from the lungs to the rest of the body. Purified hemoglobin solutions may form an interesting class of BS. However,
it suffers from some limitations such as the presence of any contaminated RBC during purification which can make it toxic. Moreover, purified hemoglobin may also suffer from rapid clearance (due to the formation of haemoglobinhaptoglobin complex) from circulation, high colloidial osmotic pressure and finally the availability of natural human blood. Thus, to overcome such limitations, modified hemoglobin was generated using modern biotechnological techniques of polymerization, pegylation (using glutaraldehyde), cross linking (oraffinose, dextranbenzenetetracarboxylate), Bovine hemoglobin, recombinant modification, transgenic human hemoglobin and microencapsulation of hemoglobin. To date, hemoglobinbased products constitutes a large fraction of BS.
Clinical trials (Phase I, II and III) in humans on cross linked hemoglobin and recombinant hemoglobin are ongoing. Nonetheless, at least 1 of these products is approved for use outside the United States and new clinical trials are being conducted or planned worldwide. Winslow’s company has put these ideas to test with a blood substitute called “MP4”. It contains hemoglobin molecules coated with polyethylene glycol to make them bulkier, so that the resulting fluid is thicker or more viscous than normal blood. The coating also gives MP4 a higher affinity for oxygen than other substitutes. Similarly, artificial blood made up of plastic molecules has been created by researchers at Sheffield University in the UK. The new artificial blood consists of plastic molecules with an iron atom at their core, this allows it to simulate the oxygencarrying hemoglobin in real RBCs.
Perfluorochemicals (PF) are synthetic fluids capable of carrying dissolved oxygen. They are made into fine emulsions for use as oxygen carriers. PFs have certain advantages like: they do not react with other gases, increases the oxygen solubility in the plasma compartment and facilitates efficient oxygen transfer. Furthermore, PFs can be produced in large amounts and purity can be more easily controlled. As compared to the modified hemoglobin, PFs have a much lower capacity for carrying oxygen.
The first commercially available PF was FluosaolDA 20%. The second generation PFs includes perfluorooctyl bromide and bis (perfluorobutyl) ethylene. But the major risks associated with PFs are acute toxicity or side effects.
Phase II clinical trials are being carried out especially to study whether a few novel BSs can be used to delay the need for blood transfusion in surgery when used with autologous blood techniques. “Hemoglobin based oxygen carrier201” has been tested for trauma subjects and myocardial oxygenation. Other recent members undergoing trials are “Hemospan”, “DCLHb”, “Oxyglobin” and “Hemopure”. The prospect of the current BS systems are difficult to envision as it is in its infancy but the use of BS may be considered to be immense as in battlefield resuscitation or in countries where supply of safe blood is under potential threat. But a question definitely arises; whether creating replacements for human body parts or organs that perform better than our normal bits may lead to a world of ‘superhumans’!