Blood substitutes or artificial blood or blood surrogates are substances used to carry out some functions of biological blood. The term blood substitute is also used with volume expanders but their scope is different. The better term for them is plasma substitutes and they are discussed later.
The use of oxygen-carrying blood substitutes is often called oxygen therapeutics.
The attempt to develop a viable blood substitute spans more than 7 decades.
The main types of oxygen-carrying blood substitutes [sometimes called artificial hemoglobin] being pursued are hemoglobin-based oxygen carriers (HBOC) and perfluorocarbon-based oxygen carriers (PFBOC).
Despite many years of research, the ideal blood substitute continues to elude researchers.
Different types of blood substitutes are still in trial stages.
A blood substitute, when developed can play a major role in trauma care, elective surgeries, conditions needing of long-term blood transfusions and chemotherapy etc.
Characteristics of an Ideal Blood Substitute
An ideal blood substitute
- Should lack antigenicity
- Eliminate or substantially reduce transmission of infection
- Be readily available
- Have a long half-life
- Should be capable of being stored at room temperature
- Carry a reasonable amount of oxygen
Oxygen-carrying Blood substitutes
The initial goal of oxygen carrying blood substitutes is to mimic blood’s oxygen transport capacity.
There are two types of oxygen therapeutics. The first is perfluorocarbons , chemical compounds which can carry and release oxygen.
The second type is haemoglobin derived from humans, animals, or artificially via recombinant technology, or via stem cell production of red blood cells in vitro.
Perfluorocarbons are chemically inert molecules containing fluorine and carbon atoms which can dissolve large amounts gases, including oxygen.
Perfluorocarbons are removed from the body by exhalation.
Oxygent was a perfluorocarbon that showed great promise initially but trials have been stopped due to increased incidence of stroke in treated patients.
Perftoran and Oxycyte are other products undergoing trials.
Hemoglobin-based products are called hemoglobin-based oxygen carriers. Pure hemoglobin are toxic to kidneys and not very useful to carry oxygen too.
cross-linking, polymerization, and encapsulation are the various processes to make hemoglobin useful.
Hemospan, is a PEG-conjugated human hemoglobin currently undergoing clinical trials in the US and Europe.
So is pyridoxylated hemoglobin polyoxyethylene conjugate (PHP) is a conjugated hemoglobin.
PolyHeme (Northfield Laboratories Inc., Evanston, Ill) is a first-generation pyridoxylated polymerized hemoglobin made from outdated human blood.
Hemopure [Biopure Corporation, Cambridge] and HemoLink (Hemosol Corporation, Mississauga, Canada) are other products.
Hemopure is a polymerized form of bovine hemoglobin and is approved in South Africa for the treatment anemia before surgery.
Hyperbranched polymer-protected porphyrins
University of Sheffield created this. It is called artificial blood which has a shelf life of 35 days.
The “plastic” blood consists of an iron-containing porphyrin which is permanently bonded to a hyperbranched polymer that protects the porphyrin.
Adverse Effects Related to Blood Substitutes
- Aabdominal pain
- Skin rash
- Elevation in lipase levels
Most of these side effects were transient.
One of the most urgent requirements in a patient suffering from acute blood loss is the re-establishment of a normal blood volume. This may be achieved satisfactorily with a number of plasma substitutes.
Human albumin 4.5 per cent can be used whilst cross-matching is being performed. Two to three units (1.2 litres) are given intravenously over 30 minutes. It is especially valuable in patients with burns with severe loss of protein.
Dextrans are polysaccharide polymers of varying molecular weight producing an osmotic pressure similar to that of plasma. They have the disadvantage of inducing rouleaux [stacks or aggregations of red blood cells ] of the red cells and this interferes with blood-grouping and cross-matching procedures.
Therefore, the blood sample should be drawn beforehand. Dextrans interfere with platelet function and may be associated with abnormal bleeding.
Total volume of dextran should not exceed 1000 ml.
Low-molecular-weight dextran has an immediate effect in a restoring plasma volume, but it is transitory because the small molecules are readily excreted by the kidney. It may be useful in preventing sludging of red cells in small blood vessels, for example of the kidney, and thus preventing the renal shutdown associated with severe hypotension. It is less likely to induce rouleaux formation than the high-molecular-weight compounds.
The high-molecular-weight dextrans are less effective in the early phase of hypovolemia but are longer acting as they are retained for some time within the circulation.
Gelatin in a degraded form is used as a plasma expander. Hemaccel and Gelafusine are contain gelatin and are given intravenously.