Blood transfusion is a life-saving procedure, but is not always feasible due to the risks associated, and the limited supply of blood. This has resulted in the development of several alternatives to blood transfusion, like blood substitutes, volume expanders, growth factors, etc.
Did You Know?
Every two seconds, someone in the US needs blood, and to satisfy the entire nation’s blood demand for one minute, about three gallons of blood is required.
Allogeneic blood transfusion (transfusion of blood donated by someone else) is a routine procedure in patient blood management to combat blood loss and the resulting iron-deficiency anemia. It may be required in the event of heavy blood loss due to accidents, during exhaustive surgeries, or as a part of the treatment for diseases like sickle cell anemia and certain cancers.
However, blood transfusion has its own set of risks and hurdles, like transmission of infectious agents and allergies, altered immune function of the recipient, short shelf-life of blood, costs involved, huge lag in the supply and demand for blood, and violation of certain religious beliefs that consider blood as a sacred substance.
Owing to these difficulties, it becomes imperative to manage patient blood efficiently and reduce the need for transfusion; as well as develop alternatives for blood and/or blood components. The loss of blood disrupts the fluid balance of the body, and leads to iron deficiency anemia, and reduced oxygen transport to the body tissues. The alternatives to blood transfusion are developed with the aim to combat these effects of blood loss.
Nevertheless, till today, there is no substance or fluid that can completely substitute human blood. Given below is a brief overview of the autologous blood transfusion methods used as a part of bloodless medicine, and other available alternatives to blood transfusion.
Bloodless medicine refers to a collection of methods that reduce the need for transfusion, and adopt autologous blood if blood transfusion is required. These are being commonly explored as an alternative to allogeneic blood transfusion.
Bloodless medicine involves a combination of one or more of the following options:
► Pre- and post-operative administration of growth factors like erythropoietin, and specific diet to enhance formation of red blood cells, as well as iron supplements to avoid iron-deficiency anemia.
► Use of chemical agents like Novoseven, Tranexamic Acid, etc., that prevent excessive bleeding during the surgery.
► Preoperative blood salvage, or collection of patient’s blood before the surgery, so that it can be transfused if required during surgery. The practice of such autologous transfusion is now declining due to the risk of inducing perioperative anemia in the patient.
► Perioperative blood salvage (or cell salvage technique) involves collection of the patient’s blood from the incision site during surgery, followed by washing or filtering it for toxins and contaminants, and reinfusing it into the patient.
Note: In case of cancer patients, autologous transfusion carries a high risk of introducing cancer cells back in the body.
Non-blood Volume Expanders
The volume of body fluids needs to be maintained for the efficient circulation of blood throughout the body. In addition, the oxygen-carrying capacity of the blood is always in excess than that required for daily activities. Hence, in patients where a modest amount of blood is lost, compensating the volume of fluid seems to be a less risky option than blood transfusion. This lost volume is compensated by a set of substances called volume expanders.
Volume expanders are intravenously administered fluids that help to maintain the circulatory volume. Moreover, the reduced concentration of hemoglobin due to such dilution of blood, triggers the natural mechanisms for red blood cell synthesis. The two major types of non-blood volume expanders available are:
► Crystalloids: These are solutions containing water, mineral salts, electrolytes, and other water-soluble substances. Normal saline, a solution of salt and water, is an example of such volume expanders. Other commonly used ones are Ringer’s solution (aqueous solution of calcium chloride, potassium chloride, sodium chloride, and sodium lactate), and intravenous sugar solutions containing dextrose.
► Colloids: This set of volume expanders contains macromolecules, like proteins, starch, and other insoluble molecules. Colloids may be prepared using hydroxyethyl starch (HES) like pentastarch and hetastarch, purified protein fractions, albumin, and the biopolymer dextran.
Although there is no real substitute for blood; certain substances that can perform the main function of blood—oxygen transport—are being developed. These are also known as oxygen-carrying blood substitutes, or artificial blood. Most of them are still under clinical trials, and those approved are rarely used. These blood substitutes are currently being developed from perfluorocarbons or are derived from hemoglobin.
► Hemoglobin-based Substitutes: Hemoglobin is the protein that confers the ability of oxygen-transport to the blood. But the administration of pure hemoglobin solution induces renal toxicity, and hence the need to modify the hemoglobin molecules in such a way that they are nontoxic, but still retain the oxygen-carrying capacity, is required. This is achieved by introducing internal cross-linking in the hemoglobin molecule (intramolecular cross-linking), polymerizing hemoglobin molecules together using agents like O-raffinose and glutaraldehyde, and by encapsulating hemoglobin molecules inside artificially prepared membranous vesicles called liposomes or artificial red blood cells called neohemocytes.
Examples: Hemopure (Phase III trials in USA), Hemospan (Phase II trials in USA), Hemotech (Phase I trials in USA), Oxyglobin (approved for veterinary use in USA and Europe)
► Perfluorocarbon-based Substitutes: Perfluorocarbons (PFCs) are compounds containing carbon and fluorine, and are useful because they are non-toxic, chemically inactive, and are not metabolized by the body tissues. The unique property of these colorless fluids is that they can easily carry oxygen in the dissolved state. Moreover, PFCs are merely 0.2 µm in diameter, and are much smaller in size than red blood cells which have a diameter of 7–8 µm. Hence, they can reach the small capillaries more efficiently as compared to RBCs.
Examples: Perftoran (Approved for use in Mexico), Oxygent (Phase II trials in USA), PHER-O2 (under development in USA).
Blood pharming refers to the process of obtaining red blood cells from stem cells isolated from umbilical cord blood. O negative RBCs are currently being manufactured on a large scale by a Cleveland-based company called Arteriocyte. These RBCs contain a hemoglobin concentration similar to normal RBCs, and can be transfused into individuals of any blood type. Although the FDA has approved the safety of this O negative blood, human trials are still pending. Nevertheless, if successful, one can hope that large-scale manufacturing will reduce the costs associated, as well as meet the ever-rising demand for blood.
Although several alternatives are available to compensate for the loss in volume and functionality of blood, there remain cases where blood transfusion cannot be avoided. The feasibility of using alternatives like those mentioned above, depends on several parameters, including the general physiology of the patient, his initial blood volume, the type of surgery or medical procedure to be implemented, and the precise vital stats during surgery. On the contrary, they remain a questionable option in case of accidents and mishaps that lead to severe blood loss.
The hunt for an appropriate alternative to blood transfusion that began about 150 years ago, continues even today.