Blood Substitutes

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Blood Substitutes Mara Atwood

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Blood Substitutes. 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. [ 1]. (1868-1943 ) Karl Landsteiner (1901) Blood of two people under contact agglutinates - PowerPoint PPT Presentation

Transcript of Blood Substitutes

Page 1: Blood Substitutes

Blood SubstitutesMara Atwood

Page 2: Blood Substitutes

Outline

Discovery of blood Important tasks of blood Why blood substitutes? Some current developments and products Risks and Benefits

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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]

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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

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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

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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

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Current Developments

Derived from Hemoglobin: Hemoglobin-based Oxygen Carriers (HBOCs)

Those that use perfluorocarbon emulsions

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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

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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

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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)

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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

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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

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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.

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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

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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

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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

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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

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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

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Thank You