A blood substitute (also
called artificial blood or blood surrogate) is a substance used
to mimic and fulfill some functions of biological blood. It aims to provide an
alternative to blood transfusion, which is transferring blood or blood-based
products from one person into another. Thus far, there are no well-accepted oxygen-carrying
blood substitutes, which is the typical objective of a red blood cell
transfusion; however, there are widely available non-blood volume expanders for
cases where only volume restoration is required. These are helping doctors and
surgeons avoid the risks of disease transmission and immune suppression,
address the chronic blood donor shortage, and address the concerns of Jehovah's
Witnesses and others who have religious objections to receiving transfused
blood.
The main categories of 'oxygen-carrying' blood substitutes being pursued are hemoglobin-based oxygen carriers (HBOC) and perfluorocarbon-based oxygen carriers (PFBOC). Oxygen therapeutics are in clinical trials in theU.S.
and Europe, and Hemopure is available in South Africa
An oxygen-carrying blood substitute, sometimes called artificial haemoglobin, is an artificially made red blood cell substitute whose main function is to carry oxygen, as does natural hemoglobin. The use of oxygen-carrying blood substitutes is often called oxygen therapeutics to differentiate from true blood substitutes. The initial goal of oxygen carrying blood substitutes is merely to mimic blood's oxygen transport capacity. There is additional longer range research on true artificial red and white blood cells which could theoretically compose a blood substitute with higher fidelity to human blood. Unfortunately, oxygen transport, one function that distinguishes real blood from other volume expanders, has been very difficult to reproduce.
There are two basic approaches to constructing an oxygen therapeutic. The first is perfluorocarbons (PFC), chemical compounds which can carry and release oxygen. The specific PFC usually used is either perfluorodecalin or dodecafluoropentane emulsion (DDFPe). The second approach is haemoglobin derived from humans, animals, or artificially via recombinant technology, or via stem cell production of red blood cells in vitro.
Oxygen therapeutics, even if widely available, would not eliminate the use of human blood, which performs various functions besides oxygen transport. However oxygen therapeutics have major advantages over human blood in various situations, especially trauma.
Blood substitutes are useful for the following reasons. Although the blood supply in many countries is very safe, this is not the case for all regions of the world. Blood transfusion is the second largest source of new HIV infections inNigeria Africa , it is believed that as much
as 40% of the population has HIV/AIDS, although testing is not financially
feasible. A disease-free source of blood substitutes would be incredibly
beneficial in these regions.
In battlefield scenarios, it is often impossible to administer rapid blood transfusions. Medical care in the armed services would benefit from a safe, easy way to manage blood supply.
Great benefit could be derived from the rapid treatment of patients in trauma situations. Because these blood substitutes do not contain any of the antigens that determine blood type, they can be used across all types without immunologic reactions.
While it is true that receiving a unit of transfused blood in theUS
Transfused blood is currently more cost effective, but there are reasons to believe this may change. For example, the cost of blood substitutes may fall as manufacturing becomes refined.
Blood substitutes can be stored for much longer than transfusable blood, and can be kept at room temperature. Most haemoglobin-based oxygen carriers in trials today carry a shelf life of between 1 and 3 years, compared to 42 days for donated blood, which needs to be kept refrigerated.
Blood substitutes allow for immediate full capacity oxygen transport, as opposed to transfused blood which can require about 24 hours to reach full oxygen transport capacity due to 2,3‑diphosphoglycerate depletion. Also, in comparison, natural replenishment of lost red blood cells usually takes months, so an oxygen-carrying blood substitute can perform this function until blood is naturally replenished.
Oxygen-carrying blood substitutes also would become an alternative for those patients that refuse blood transfusions for religious or cultural reasons, such as Jehovah's Witnesses.
Synthetic oxygen carriers may also show potential for cancer treatment, as their reduced size allows them to diffuse more effectively through poorly vasculated tumour tissue, increasing the effectiveness of treatments like photodynamic therapy and chemotherapy.
TheU.S.
Haemoglobin-based blood substitutes may increase the odds of deaths and heart attacks.
According to studies of outcomes of transfusions given to trauma patients in 2008, blood substitutes yielded a 30% increase in the risk of death and about a threefold increase in the chance of having a heart attack for the recipients. More than 3,711 patients were tested in sixteen studies using five types of artificial blood. Public Citizen sued the U.S. Food and Drug Administration (FDA) to obtain information on the duration of these studies which were found to have been conducted from 1998 until 2007. The FDA permits artificial blood transfusions in theUS
The functions of blood are many. Normally, for example, white blood cells defend against disease, platelets allow clotting, and blood proteins perform various functions. In addition, the blood composition includes additional molecules and electrolytes to function properly. Some of these components are substitutable with modern technology, and may, at least, be added to an oxygen-carrying blood substitute to create a more complete blood substitute.
Volume expanders could conceptually be called blood substitutes as well, but they are usually not within the scope of blood substitutes. Still, they are sometimes called "plasma substitutes".
The main categories of 'oxygen-carrying' blood substitutes being pursued are hemoglobin-based oxygen carriers (HBOC) and perfluorocarbon-based oxygen carriers (PFBOC). Oxygen therapeutics are in clinical trials in the
Oxygen Carrying Substitutes
An oxygen-carrying blood substitute, sometimes called artificial haemoglobin, is an artificially made red blood cell substitute whose main function is to carry oxygen, as does natural hemoglobin. The use of oxygen-carrying blood substitutes is often called oxygen therapeutics to differentiate from true blood substitutes. The initial goal of oxygen carrying blood substitutes is merely to mimic blood's oxygen transport capacity. There is additional longer range research on true artificial red and white blood cells which could theoretically compose a blood substitute with higher fidelity to human blood. Unfortunately, oxygen transport, one function that distinguishes real blood from other volume expanders, has been very difficult to reproduce.
There are two basic approaches to constructing an oxygen therapeutic. The first is perfluorocarbons (PFC), chemical compounds which can carry and release oxygen. The specific PFC usually used is either perfluorodecalin or dodecafluoropentane emulsion (DDFPe). The second approach is haemoglobin derived from humans, animals, or artificially via recombinant technology, or via stem cell production of red blood cells in vitro.
Motivation for Research on
Substitutes for Blood
Oxygen therapeutics, even if widely available, would not eliminate the use of human blood, which performs various functions besides oxygen transport. However oxygen therapeutics have major advantages over human blood in various situations, especially trauma.
Blood substitutes are useful for the following reasons. Although the blood supply in many countries is very safe, this is not the case for all regions of the world. Blood transfusion is the second largest source of new HIV infections in
In battlefield scenarios, it is often impossible to administer rapid blood transfusions. Medical care in the armed services would benefit from a safe, easy way to manage blood supply.
Great benefit could be derived from the rapid treatment of patients in trauma situations. Because these blood substitutes do not contain any of the antigens that determine blood type, they can be used across all types without immunologic reactions.
While it is true that receiving a unit of transfused blood in the
Transfused blood is currently more cost effective, but there are reasons to believe this may change. For example, the cost of blood substitutes may fall as manufacturing becomes refined.
Blood substitutes can be stored for much longer than transfusable blood, and can be kept at room temperature. Most haemoglobin-based oxygen carriers in trials today carry a shelf life of between 1 and 3 years, compared to 42 days for donated blood, which needs to be kept refrigerated.
Blood substitutes allow for immediate full capacity oxygen transport, as opposed to transfused blood which can require about 24 hours to reach full oxygen transport capacity due to 2,3‑diphosphoglycerate depletion. Also, in comparison, natural replenishment of lost red blood cells usually takes months, so an oxygen-carrying blood substitute can perform this function until blood is naturally replenished.
Oxygen-carrying blood substitutes also would become an alternative for those patients that refuse blood transfusions for religious or cultural reasons, such as Jehovah's Witnesses.
Synthetic oxygen carriers may also show potential for cancer treatment, as their reduced size allows them to diffuse more effectively through poorly vasculated tumour tissue, increasing the effectiveness of treatments like photodynamic therapy and chemotherapy.
The
Risks
Haemoglobin-based blood substitutes may increase the odds of deaths and heart attacks.
According to studies of outcomes of transfusions given to trauma patients in 2008, blood substitutes yielded a 30% increase in the risk of death and about a threefold increase in the chance of having a heart attack for the recipients. More than 3,711 patients were tested in sixteen studies using five types of artificial blood. Public Citizen sued the U.S. Food and Drug Administration (FDA) to obtain information on the duration of these studies which were found to have been conducted from 1998 until 2007. The FDA permits artificial blood transfusions in the
Other Functions than Carrying
Oxygen
The functions of blood are many. Normally, for example, white blood cells defend against disease, platelets allow clotting, and blood proteins perform various functions. In addition, the blood composition includes additional molecules and electrolytes to function properly. Some of these components are substitutable with modern technology, and may, at least, be added to an oxygen-carrying blood substitute to create a more complete blood substitute.
Volume expanders could conceptually be called blood substitutes as well, but they are usually not within the scope of blood substitutes. Still, they are sometimes called "plasma substitutes".
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