Author: Tilda Barliya PhD
“Artificial blood” has been the main focus of research in the past few years (1) and refers to a substance used to mimic and fulfill some functions of biological function.
A number of driving forces have led to the development of artificial blood substitutes (1):
- The military, which requires a large volume of blood products that can be easily stored and readily shipped to the site of casualties.
- HIV; with the advent of this virus, the medical community and the public suddenly became aware of the significance of transfusion-transmitted diseases and became concerned about the safety of the national blood supply.
- The growing shortage of blood donors. Approximately 60% of the population is eligible to donate blood, but fewer than 5% are regular blood donors.
- Short shelf-life of the blood products.
- High hospital needs: cancer patients, transplantation etc
Artificial blood products offer many important benefits:
- Readily available
- Have a long shelf life
- Can undergo filtration and pasteurization processes
- Do not require blood typing (i.e A,B AB, O)
- Do not appear to cause immunosuppression in the recipient.
Researchers have focused their efforts on creating artificial substitutes for 2 important functions of blood: A) oxygen transport by red blood cells and B) hemostasis by platelets (1).
A) Red Cell Substitutes:
- Hemoglobin based
- Perfluorocarbon (PFC) based
A1) Hemoglobin-based
The hemoglobin-based substitutes use hemoglobin from several different sources (1):
- Human – Human hemoglobin is obtained from donated blood that has reached its expiration date and from the small amount of red cells collected as a by-product during plasma donation.
- Animal – Animal hemoglobin is obtained from cows. This source creates some apprehension regarding the possible transmission of animal pathogens, specifically bovine spongiform encephalopathy.
- Recombinant – Recombinant hemoglobin is obtained by inserting the gene for human hemoglobin into bacteria and then isolating the hemoglobin from the culture.
Understanding hemoglobin, its transition from a monomer to a tetramer and the way it needs to be linked to the surface of the artificial blood cells is of major issue and will be discussed in more depth in part II.
A2) Perfluorocarbon (PFC) based
PFCs are synthetic hydrocarbons with halide substitutions and are about 1/100th the size of a red blood cell. These solutions have the capacity to dissolve up to 50 times more oxygen than plasma. Because PFC solutions are modified hydrocarbons, however, they do not mix well with blood and must be emulsified with lipids or oils. The PFCs are inert products. After infusion, the molecules vaporize and are then exhaled over several days (1).
B) Platelet Substitutes:
Platelets are also at very high need due to their extremely short shelf-life (5 days) and very limited supply. Several methods have been utilized to create platelet substitutes including:
- Infusible platelet membranes
- Thrombospheres
- Lyophilized human platelet product
Use and need for HLA antigen or platelet antigens, fibrinogen proteins and aggregation factors will be further discussed in part II.
In Summary:
The growing need for blood supply due to short shelf-life, limited supply and increase in disease/injured population have urged researchers to look for blood substitutes. Although the many years of research and profound progress that have been made, there’s plenty of disadvantages having complications and limited clinical benefits. The topic of blood substitutes will be further discussed in part II, highlighting the different substitutes that were developed, those which entered clinical trails, and the potential use of nanotechnology in this field of research.
Reference:
1. Lesley Kresie. Artificial blood: an update on current red cell and platelet substitutes. Proc (Bayl Univ Med Cent). 2001 April; 14(2): 158–161 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1291332/
2. By: Tony Rairden. Synthetic Red Blood Cells Developed. http://www.nanotech-now.com/news.cgi?story_id=35993
3. By: Abdu I. Alayash. BLOOD SUBSTITUTES: Working to Fulfill a Dream. FDA voice. http://blogs.fda.gov/fdavoice/index.php/2012/06/blood-substitutes-working-to-fulfill-a-dream/
4. Jiin-Yu Chen, Michelle Scerbo, and George Kramer. A Review of Blood Substitutes: Examining The History, Clinical Trial Results, and Ethics of Hemoglobin-Based Oxygen Carriers. Clinics (San Paulo) 2009 August; 64(8): 803-813. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2728196/
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I look forward to Part II. I have over 20 years of experience in Blood Banking, beginning at the time of emergence of HIV, but let us not forget HCV, which will become an increased burden over time. It became incumbent on me to deal with utilization by creating and validating a surgical blood order schedule, determining the amount of loss and the amount transfused by procedure, and supporting a Level 1 trauma Service. I had to show graphical results at the monthly Transfusion Committee, and that had an impact. It required that I obtain sponge counts from the surgical reports. Recapture of blood during surgery has helped. I attended Red Cross advisory committee meetings monthly for years.
There was a time that physicians thought that they had to have “whole blood”. No such thing., Every unit is fractionated, and every unit is tested. I did some medicolegal work in those days, and had difficult cases referred to me from outside my own state by one of the best medicolegal experts in the country. In one case a man developed HIV post-transfusion, and it happened because the blood was tested and the unit was initially returned unused, but it was sent out determined positive and transfused. It was a violation of the standard of practice.
The greatest risk in RBC transfusions 50 years ago was in ABO mismatch, RH, Kell, and Duffy. I did encounter an Rh incompatibility involving a woman who was divorced, had her fallopian tubes tied, then remarried and had them untied, and there was the incompatibility, which resulted in hemolytic disease of the newborn with hyperbilirubinemia.
The enormous effort to produce PFCs was tested in trauma surgery. The results were very suboptimal.
The interest in platelets is without a doubt the most critical. Platelets have a 7 day shelf life after the blood is removed. The blood is processed and tested, so the blood in the blood bank of the hospital has a life of maybe 3-4 days, and is essentially not returnable. The platelets may be received by the hospital before all of the testing is completed, so it’s possible for the blood to be transfused, and the laboratory to receive a product notification after the transfusion. There is no comparison to the quality and documentation followed by the blood bank in any other part of the hospital. In addition, I was in charge of the bone storage and safety for at least 15 years. It is another very high risk area, not usually handled by the laboratory. It spurned enormous work in developing chemical decontamination.
The servicing of blood for oncology is difficult. There is great care to avoid GVH disease. This is related to any presence of immunocompetent cells that can multiply and attack the recipient.
Dr. Larry,
Thank you for your comment, above, by a very experienced Lab physician, among ten other titles you deserve.
Dr. Tilda,
Thank you for Part I on this very important topic in the Lab development of Synthetic biologics, some do treat and refer to Blood as an Organ, even skin, is treated by some as an Organ.
I am eager to read your forthcoming Part II.
Point 2 above, is in fact three stand alone points,thus, you will have 7 not 5.
Please conduct a Search on our Journal on Coagulation, you may consider some of the search results suitable to be added to this article.
Thank you again