Is there a substitute for human blood?
While there is no synthetic substitute for human blood, current research largely focuses on developing substitute blood components, like platelets for clotting or red cells for oxygen/CO2 exchange.
Though some clinical trials of blood substitutes have shut down because of safety concerns, the field has come a long way since early doctors tried various disastrous experimental blood alternatives like animal blood, milk and wine.
Ongoing research to develop platelet substitutes was in pre-clinical animal testing in summer of 2020. Currently, the only clinical product in use are saline solutions to expand the volume of blood, which maintains blood pressure and allows red cells to keep working and regenerating.
The ultimate object of research is to create a substitute blood product that will be safe to use and can carry out all the human blood functions. Currently, there is no FDA-approved oxygen-carrying blood substitute product commercially available.
What is human blood made of?
- Red blood cells transport oxygen from the lungs to the various organs in the body and carry back carbon dioxide to the lungs to be expelled with exhalation.
- White blood cells fight infections.
- Platelets clot the blood in injuries, stop the bleeding and help heal the wounds.
- Plasma is composed of mostly water with salts and enzymes, and is the medium for the blood cells and platelets to circulate in the body.
What is artificial blood and why is it used instead of real blood?
Artificial blood is a theoretical substitute blood product that can carry out the most vital function of blood, which is the transport of oxygen and carbon dioxide. Artificial blood could be a life-sustaining measure, especially in times of serious blood loss during large disasters; however, the products in development right now cannot carry out secondary functions of blood such as fighting infections.
There are several reasons why the scientific community is working on developing artificial blood to use instead of real blood:
- Prevention of complications of real blood transfusion such as:
- Immune reactions to the blood.
- Risk of infections.
- Donor blood must match the blood type of the recipient.
- Blood must be refrigerated, and has a shelf-life of 42 days, while artificial blood products in development can be freeze-dried and stored at room temperature for up to two years.
- Donor blood requires tests for hepatitis, human immunodeficiency virus (HIV) and other such pathogens, which drive up the cost of transfusion.
- Though the tests are highly sophisticated, risk of infection cannot be entirely ruled out.
- With the number of surgeries on the increase, the number of people needing blood has gone up. With an aging population, the need for blood is not matched by the number of donors who are willing/able to donate.
- In emergency situations or in remote places, immediate availability of artificial blood could save lives, as it is sterile and no blood type matching is required.
- Artificial blood could potentially deliver oxygen faster than real blood during an emergency, and may minimize injury to the tissue, particularly during a heart attack.
- Blood substitutes could benefit people with blood disorders who need regular long-term blood transfusions, such as patients with:
- Blood substitutes may be used to preserve donor organs better, and prevent reperfusion injury (organ tissue injury from return of blood supply).
- Artificial blood may be of use for certain ethnic and religious groups of people who have concerns about human blood-derived products.
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Why are artificial blood products needed?
Artificial blood products could be potentially life-saving in emergency situations. Clinical trials are in progress for their use in specific medical situations that include:
- Delivery of oxygen after a traumatic brain injury, directly to the injured brain tissue.
- Providing oxygen after heavy blood loss from injury, while the body stabilizes.
- Providing oxygen during surgery that may cause significant blood loss.
- Maintaining oxygen flow to cancerous tissue, in order to make chemotherapy more effective.
- Oxygen delivery to tissues affected by sickle-cell anemia and as treatment of certain other severe kinds of anemia.
What is artificial blood made of?
Scientists are working on two types of artificial blood substitutes that carry out the function of transporting oxygen and carbon dioxide.
Perfluorocarbon emulsions (PFCs)
Perfluorocarbons (PFCs) are entirely synthetic, inert molecules containing fluorine and carbon atoms. These molecules are capable of dissolving many gases including oxygen. Perfluorocarbons can carry more oxygen than red blood cells do.
Perfluorocarbons are hydrophobic (water-repellant), so they are first emulsified in another substance before intravenous injection. The fine, emulsified droplets break down inside the blood vessel, and the PFC circulates in the blood releasing oxygen.
The PFC eventually is released through the lungs as the person exhales, like carbon dioxide is processed out of the lungs, and the liver and kidney eliminate the emulsifiers.
Hemoglobin-based oxygen carriers (HBOCs)
Hemoglobin, which is found in the blood is the natural oxygen carrier, and substitute blood products made with hemoglobin are a major area of research. Hemoglobin may be extracted from several sources such as:
- Human red blood cells from outdated blood
- Red blood cells from cow’s (bovine) blood
- Bacteria such as Escherichia coli genetically modified to produce hemoglobin
- Human placenta
Hemoglobin without the cell membrane (stroma-free hemoglobin), disintegrates very quickly and can cause clotting disorders, hypertension and kidney damage. Researchers developing this kind of experimental blood substitute must purify and modify the hemoglobin to make it more stable.
Many techniques have been used in the attempt to stabilize the hemoglobin, which include the following:
- Diaspirin cross-linked hemoglobin (DCLHb): Hemoglobin that is modified and stabilized by cross-linking portions of the hemoglobin molecule using a cross-linking agent.
- Recombinant hemoglobin: Genetically engineered variant of hemoglobin produced by using Escherichia coli.
- Polymerized hemoglobin: Multiple hemoglobin molecules bound together to form a polymer, using human or bovine hemoglobin.
Some of the next-generation blood products under research are:
- Conjugated hemoglobin: Hemoglobin bonded with a synthetic polymer to improve the efficacy of oxygen delivery. The types of conjugated hemoglobin are:
- Polyethylene glycol conjugated with bovine hemoglobin evaluated for use in cancer therapy, and now discontinued.
- Polyethylene glycol conjugated with human hemoglobin (MP4OX), currently undergoing clinical trials.
- Pyridoxylated hemoglobin polyoxyethylene conjugate (PHP), currently undergoing clinical trials on patients with shock from systemic inflammatory response syndrome.
- Hemoglobin cross-linked with enzymes: Other compounds synthesized with hemoglobin in order to create a blood product that can carry out other red blood cell functions such as removal of free radicals, besides carrying oxygen.
- Hemoglobin wrapped in a fatty capsule: To retain the hemoglobin for a longer period in the plasma and prevent its binding with nitric oxide which causes hypertension.
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What are the adverse effects of blood substitutes?
No blood substitute currently meets the criteria for approval of use in patients. Many are undergoing clinical trials, and some have been discontinued because of safety factors and serious side effects.
Perfluorocarbon emulsions
Only one perfluorocarbon product Fluosol-DA received FDA approval in 1989, which was withdrawn in 1994 because of low efficacy and oxygen carrying capacity, besides side effects.
Side effects of PFCs include:
- Lung damage
- Increased incidence of stroke in treated patients
Hemoglobin-based oxygen carriers
FDA has not approved any hemoglobin-based oxygen carriers so far, though several are undergoing clinical trials. Research labs are addressing efficacy and safety issues.
Trials in some of the first-generation artificial blood products have been discontinued because of side effects. The new generation blood substitutes have a better side effect profile, but are still in the trial phase.
Side effects of HBOCs include:
- Hypertension
- Abdominal pain
- Skin rash
- Diarrhea
- Jaundice
- Hemoglobinuria (stroma-free hemoglobin in the urine)
- Oliguria (low urine output)
- Fever
- Increased risk for stroke and heart attack
- Backache
- Gastrointestinal problems