Mara Atwood Outline Discovery of blood Important tasks of blood Why blood substitutes Some current developments and products Risks and Benefits Discovery of Blood Groups 18681943 Karl Landsteiner ID: 414875
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Slide1
Blood Substitutes
Mara Atwood Slide2
Outline
Discovery of blood
Important tasks of blood
Why blood substitutes?
Some current developments and products
Risks and Benefits Slide3
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]Slide4
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 CellsImmune Response Platelets
Blood Clotting, wound healing Slide5
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 ShortagesShort-term replacement of blood during surgery Slide6
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 pathogensEffectively deliver oxygen to tissuesSlide7
Current Developments
Derived from Hemoglobin: Hemoglobin-based Oxygen Carriers (
HBOCs
)
Those that use
perfluorocarbon emulsions Slide8
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 heatSlide9
Hemoglobin Products
Polyheme
-polymerized human hemoglobin product
Northfield Laboratories
Hemopure-polymerized hemoglobin from bovine red blood cells Biopure/BiotechApproved in South Africa Phase III clinical trials in U.S.
Hemolink-partially polymerized human hemoglobinHemsosol
Under FDA ReviewSlide10
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)Slide11
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 Slide12
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 typesSlide13
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. Slide14
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 farSlide15
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 Slide16
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.htmlSlide17
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 subjectsDifficulty in storage and re-use-production endedOxygent
Developed by Alliance PharmaceuticalsStage 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-0001Slide18
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 increasedCost needs to be competitive
Obtaining and processing sufficient amounts must be overcomeSlide19
Thank You