Blood SubstitutesMara Atwood
Outline
Discovery of blood Important tasks of blood Why blood substitutes? Some current developments and products Risks and Benefits
Discovery of Blood Groups
(1868-1943 ) Karl Landsteiner (1901) Blood of two people under
contact agglutinates Due to blood serum (blood
plasma) Identified blood groups A, B, C
(later named O) (1907) First successful blood
transfusion (Reuben Ottenberg, Mount Sinai Hospital, New York)
[1]
Principle Tasks of Blood
Transport Oxygen throughout body Release oxygen to tissues – pick up carbon Hemoglobin- Oxygen-carrying protein containing
erythrocytes (Red Blood Cells)
White Blood Cells Immune Response
Platelets Blood Clotting, wound healing
Reasons For Blood Substitutes
Human RBC have strict storage requirements Designed to prolong clinical effectiveness, reduce
risk bacterial infection
Blood Substitutes more amenable to sterilization
Do not require cross-matching
Donor Blood Shortages Short-term replacement of blood during surgery
The Ideal Blood Substitute
Require no cross-matching, compatibility testing
Suitable for long-term storage (room temperature)
Survive circulation for several weeks (intravascular “dwell” time) before being cleared by kidney
Side-effect free Free of pathogens Effectively deliver oxygen to tissues
Current Developments
Derived from Hemoglobin: Hemoglobin-based Oxygen Carriers (HBOCs)
Those that use perfluorocarbon emulsions
Hemoglobin-Based Oxygen Carriers
Cell-free solution of hemoglobin as a blood substitute
Hemoglobin maintains ability to transport oxygen outside of red blood cells
Compatibility testing not required Can be sterilized by ultrafiltration and low
heat
Hemoglobin Products
Polyheme-polymerized human hemoglobin product Northfield Laboratories
Hemopure-polymerized hemoglobin from bovine red blood cells
Biopure/Biotech Approved in South Africa Phase III clinical trials in U.S.
Hemolink-partially polymerized human hemoglobin Hemsosol Under FDA Review
Polyheme Uses expired human blood Hemoglobin solution, no intact red blood cells Manufacturing steps reduce risk of viral
infection Shelf life of 12 months Can be stored at room temperature Only provides oxygen carrying capacity Intravascular dwell time shorter than 120 days
(RBC)
Clinical Trials
Finished Phase III trauma trial in June 2006 December 19, 2006 preliminary results
released 13.2% died vs. 9.6% control group Re-evaluation of study database-no new trials Result: No FDA approval thus far
Hemopure
Developed by OPK Biotech Based on chemically stabilized bovine (cattle)
hemoglobin
Use in humans as oxygen delivering bridge when blood is not available
Stable for 36 months at room temperature Compatible with all blood types
Hemopure
Carried in the plasma Transports oxygen wherever plasma flows (partial
blockages or constricted vessels) Holds same amount of oxygen as hemoglobin Release oxygen more readily Introducing Hemopure into bloodstream may help RBSc
offload more oxygen to tissues than would otherwise.
Clinical Trials
Last human test (date unknown) FDA imposed ban on further clinical trials due to safety concerns
Animal testing has been ensued Hemopure approved for human use and
commercial sale in South Africa in April 2001 Result: No FDA approval thus far
Hemolink
Developed by Hemosol Highly purified human hemoglobin-based
oxygen carrier Approved for clinical trials in primary cardiac
bypass surgery (early 2000s) Currently no FDA approval
Perfluorocarbon Perfluorocarbons
Molecules structurally similar to hydrocarbons
Hydrogen atoms replaced with fluorine atoms
Perfluorocarbon Liquids have excellent capacity for carrying oxygen and carbon dioxide
Oxygen dissolves in chemically inert perfluorocarbon liquid
Can be easily extracted by oxygen-deprived tissue
http://www.md.ucl.ac.be/virtanes/pastedoct99.html
Perfluorocarbon Products
Fluosol DA Approved by FDA as a blood substitute for heart surgery Green Cross Corp. of Japan (1989-1992) Used in more than 40,000 human subjects Difficulty in storage and re-use-production ended
Oxygent Developed by Alliance Pharmaceuticals Stage II/III clinical trials Study in 2008 As of February 2005, no FDA approval-safety
http://www.pharmaceuticalonline.com/doc/alliance-pharmaceutical-baxter-to-collaborate-0001
Risk Vs. Benefit Safety of Donor Blood Supply
Risk of transfusion-associated HIV infection as low as 1 per 185,000
Risk of transfusion-associated infection of Hepatitis C Virus (HCV) between 1 per 300,000 and 1 per 600,000- compared to 1 per 103,000 in early 1990s
New blood substitutes could potentially carry unknown risks
Intravascular dwell times need to be increased Cost needs to be competitive Obtaining and processing sufficient amounts must be
overcome
Thank You
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