Download Why Blood Substitutes?

SYNTHETIC BLOOD
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Blood Need
• Blood need for centuries
• Water, wine & opium
were used as substitutes
• Animal to human
transfusion
• 1818- James Bundell- first
human/human blood
transfusion
• During WWI & WWII
blood transfusion was
performed to a wider
extent.
Squires, Jerry E., Artificial Blood, Science, 295, 1002(2002)
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Why Blood Substitutes?
• Diseases
* 1 in 500,000 death risk of alogeneic blood
transfusion
* 1 in 180,000 HepatitisB risk
* 1 in 1.6million HIV/AIDS risk
* 1 in 1.8million immunodeficiency death risk
• Low donation ratio
* By 2030, there will be 4 million unit blood
deficiency
Henkel Hanke et al. Artificial oxygen Carriers: A Current Review, AAANA Journal, 2007, 75(3)
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Why Blood Substitutes?
• Storage Problems
• Cross-matching & compatibility testing
• Religious issues
Henkel Hanke et al. Artificial oxygen Carriers: A Current Review, AAANA Journal, 2007, 75(3)
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An Ideal Blood Substitute
• Working Principle: Mimic oxygen carrying ability of
blood
Also:
• Transferring oxygen to the tissue
• Should not be eliminated in kidney
• No compatibility
• Easy storage
Squires, Jerry E., Artificial Blood, Science, 295, 1002(2002)
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An Ideal Blood Substitute
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Henkel Hanke et al. Artificial oxygen Carriers: A Current Review, AAANA Journal, 2007, 75(3)
When to use?
• In surgeries that requires high amount of blood
transfusion
• In case of diseases that requires blood change
• War times
Brown Universty, Biomedical Department; Synthetic Blood Web Page
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When to use?
Henkel Hanke et al. Artificial oxygen Carriers: A Current Review, AAANA Journal, 2007, 75(3)
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Types
Two main types of oxygen carriers:
1. Haemoglobin Based Oxygen Carriers (HBOC)
2. Perfluorocarbon-Based Products (PFCE)
Brown Universty, Biomedical Department; Synthetic Blood Web Page
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HBOC
•
2,3 Diphospoglycerate: A product
of red blood cell pathway
•
Cell-free haemoglobin
solution
* Keeps O2 carrying ability
* No cross-matching
* Easy sterilization
(ultrafiltration)
* Long shelf-life
Taken from expired
donated blood or animal
blood
Squires, Jerry E., Artificial Blood, Science, 295, 1002(2002)
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HBOC
•
First challenge in fabrication: Elimination in kidneys
* Crosslinking Hb molecules together
* Encapsulating Hb Molecules
* Life time: 12h
Problems:
• Dependency on blood donation
• Short life time
• May cause high blood pressure& low cardiac output
Squires, Jerry E., Artificial Blood, Science, 295, 1002(2002)
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HBOC
Comparison of HBOCs to Transfused Red Blood Cells
Attribute
Infused HBOCs
Onset of
Immediate
action:
Oxygen affinity: Red cell 2,3 DPG not
required for oxygen
release
Oxygen
Red cells plus plasma
transport:
Risk of disease
Sterile
transmission: pharmaceutical; no
leukocyte exposure
Storage:
Shelf life:
Compatibility:
Preparation:
Viscosity:
Duration of
action:
Transfused Red Cells
2,3-DPG dependent
Red cell 2,3 DPG
required for oxygen
release
Red cells only
Risk minimize by
improved donor
selection; leukocyte
exposure
Room temperature;
Refrigeration
no loss of efficacy required; progressive
loss of efficacy
36 months
42 days
Universal
Type-specific
Ready to use
Requires typing and
cross-matching
Low
High
Maximum of 3 days Estimated 60 to 90
days
Brown Universty, Biomedical Department; Synthetic Blood Web Page
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HBOC Products
Hemopure: (Biopure)
• Readily used in South Africa since 2001
• In Phase III clinical trials for FDA approval (filed’02)
• Increases O2 diffusion capacity & decrease blood
transfusion need.
Hemolink: (Hemosol)
• Ongoing Phase II trials in US
• 2003- Stopping trials due to an imbalance of cardiac
events during a surgery
PolyHeme: (Northfield)
• Phase III trials
• Improving survival in vital bleeding cases
Brown Universty, Biomedical Department; Synthetic Blood Web Page
Henkel Hanke et al. Artificial oxygen Carriers: A Current Review, AAANA Journal, 2007, 75(3)
13
HBOC
Comparison of HBOCs:
Source:
Shelf-life:
Storage:
Half-life:
Approved
oxygen
therapeutics:
Product
Name:
Biopure
Bovine Hgb
Northfield
Hemosol
Expired Expired Human
Human RBCs
RBCs
3 years
1 year
1 year
Room Temperature Refrigerated Refrigerated/
Room
Temperature
18-22 hours
24 hours
14 hours
2
0
0
Hemopure &
Oxyglobin
PolyHeme
Hemolink
Brown Universty, Biomedical Department; Synthetic Blood Web Page
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PFCE
•
•
•
Oxygen dissolves in PFC solutions
Faster oxygen unloading
Not soluble in aqueous media,
emulsions are prepared
* an emulsion like solution
Brown Universty, Biomedical Department; Synthetic Blood Web Page
Squires, Jerry E., Artificial Blood, Science, 295, 1002(2002)
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PFCE
Problems:
• Biodegradibility:
* Fluorocarbons stay in the reticuloendothelial system
(RES)
* Immediate effects are good, but long term effects
are more critical.
Brown Universty, Biomedical Department; Synthetic Blood Web Page
Henkel Hanke et al. Artificial oxygen Carriers: A Current Review, AAANA Journal, 2007, 75(3)
16
PFCE Products
Fluosol DA20: (Green Cross Corp., Japan)
• First FDA approved artificial blood in 1989
• Milky solution
• To be used in cardiac surgeries
• Low PFC content, low O2 carrying capacity
(20%/volume of the solution was PFC)
• Physicians did not approve using
• Discontinued production in 1994
Brown Universty, Biomedical Department; Synthetic Blood Web Page
Henkel Hanke et al. Artificial oxygen Carriers: A Current Review, AAANA Journal, 2007, 75(3)
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PFCE Products
Oxygent ™ : (Alliance Pharmaceutical Corp.)
• Phase II/III trials for FDA approval
• Milky solution
• Reducing need of blood transfusion
• 60%/volume PFC content
Oxycyte™ (Synthetic Blood International, Inc)
PFCE PHER-02 (Sanguine Corp. )
Brown Universty, Biomedical Department; Synthetic Blood Web Page
Henkel Hanke et al. Artificial oxygen Carriers: A Current Review, AAANA Journal, 2007, 75(3)
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New Aspects
•
Prof .Dr. Luc Douay of Université Pierre et Marie
Curie-Paris has created red blood cells from stem cells
to give back the donor.
http://www.youtube.com/watch?v=axrSMFiNI3E
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• Thank
you 
Questions?
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