1. SYNTHETIC BLOOD
Eda idil çoker

2. 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)

3. 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)

4. 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)

5. 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)

6. An Ideal Blood Substitute
Henkel Hanke et al. Artificial oxygen Carriers: A Current Review, AAANA Journal, 2007, 75(3)

7. 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

8. When to use?
Henkel Hanke et al. Artificial oxygen Carriers: A Current Review, AAANA Journal, 2007, 75(3)

9. Types Two main types of oxygen carriers:
Haemoglobin Based Oxygen Carriers (HBOC)
Perfluorocarbon-Based Products (PFCE)
Brown Universty, Biomedical Department; Synthetic Blood Web Page

10. HBOC 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
2,3 Diphospoglycerate: A product of red blood cell pathway
Squires, Jerry E., Artificial Blood, Science, 295, 1002(2002)

11. 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)

12. HBOC Comparison of HBOCs to Transfused Red Blood Cells Attribute
Infused HBOCs
Transfused Red Cells
Onset of action:
Immediate
2,3-DPG dependent
Oxygen affinity:
Red cell 2,3 DPG not required for oxygen release
Red cell 2,3 DPG required for oxygen release
Oxygen transport:
Red cells plus plasma
Red cells only
Risk of disease transmission:
Sterile pharmaceutical; no leukocyte exposure
Risk minimize by improved donor selection; leukocyte exposure
Storage:
Room temperature; no loss of efficacy
Refrigeration required; progressive loss of efficacy
Shelf life:
36 months
42 days
Compatibility:
Universal
Type-specific
Preparation:
Ready to use
Requires typing and cross-matching
Viscosity:
Low
High
Duration of action:
Maximum of 3 days
Estimated 60 to 90 days
Brown Universty, Biomedical Department; Synthetic Blood Web Page

13. 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)

14. Approved oxygen therapeutics:
HBOC
Comparison of HBOCs:
Biopure
Northfield
Hemosol
Source:
Bovine Hgb
Expired Human RBCs
Shelf-life:
3 years
1 year
Storage:
Room Temperature
Refrigerated
Refrigerated/ Room Temperature
Half-life:
18-22 hours
24 hours
14 hours
Approved oxygen therapeutics: 2
Product Name:
Hemopure & Oxyglobin
PolyHeme
Hemolink
Brown Universty, Biomedical Department; Synthetic Blood Web Page

15. 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)

16. 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)

17. 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)

18. 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)

19. 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.

20. Thank you 
Questions?