Will Artificial Blood Reduce the
Need for Red Cell Transfusions
Hayden French
Richard Pugh
Jessica van der Molen
CXA333 Transfusion Science
© UTas SHS 2014 HF, RP, JvdM
Brief History of Red Cell Substitutes
• Early empirical attempts
– ale, wine, milk, animals
• 20th century
– purified haemolysate
– HIV epidemic
– HBOCs
– PFCs
• 21st century
– recombinant HBOC
CXA333 Transfusion Science
© UTas SHS 2014 HF, RP, JvdM
Nomenclature & Attributes
• Blood substitute?
• Key terms
• Attributes
– transport of respiratory gases
– lack antigenicity and disease transmission
– long half life
– prolonged storage at RT
– readily available
– no adverse effects
CXA333 Transfusion Science
© UTas SHS 2014 HF, RP, JvdM
Drivers for Development
• Military
• TTD
• HTR
• Cost
• Redundancy
CXA333 Transfusion Science
© UTas SHS 2014 HF, RP, JvdM
Design & Composition – HBOC’s
• PolyHb/Cross-Linked Hb
- via cross-linkage to reactive amino groups
• Conjugated Hb
- cross-linked to polymers
• Recombinant Hb
- produced via genetically engineered E.coli
• Encapsulated Hb
- formation of encapsulated Hb and enzymes
CXA333 Transfusion Science
© UTas SHS 2014 HF, RP, JvdM
Design & Composition – HBOC’s
CXA333 Transfusion Science
© UTas SHS 2014 HF, RP, JvdM
Design & Composition – PFC’s
•
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Mainly chemical based
Mainly composed of carbon and fluorine
Synthetic fluids oxygen can dissolve
Made into emulsions for use as oxygen
carriers
• Hydrophobic
CXA333 Transfusion Science
© UTas SHS 2014 HF, RP, JvdM
Applications
• Oxygenation of tissues in human body
• Alternative for blood transfusions
• Ready use for mass trauma incidents
• Restoration of blood volume
• Remote and emergency supply
• Alternative for religious communities
• Alleviation of decompression sickness (PFC's)
CXA333 Transfusion Science
© UTas SHS 2014 HF, RP, JvdM
Benefits
• “Universal donor”
• Avoidance of ABO and antibody incompatibility
• Less blood typing required
• Reduction of work (less mistakes, less cost!)
• Increased shelf life (RT, 36 months)
• Reduced transmission of blood borne viruses
• Increased oxygen perfusion
CXA333 Transfusion Science
© UTas SHS 2014 HF, RP, JvdM
Disadvantages: Side Effects
• Haemoglobin-Based Oxygen Carriers
– vasoconstriction
– abdominal pain, nausea/vomiting
– colloidal osmotic effect
– increased mean arterial pressure
– risk of myocardial infarct
– ?risk of prion pathogens (bovine-derived Hb)
CXA333 Transfusion Science
© UTas SHS 2014 HF, RP, JvdM
Disadvantages: Side Effects
• Perfluorocarbons
– decreased immune function
– fever, malaise and back pain
– bronchospasm
– thrombocytopaenia
– chronic anaemia
– chemical pneumonitis
Currently, risk of using AOCs outweighs the benefits…
CXA333 Transfusion Science
© UTas SHS 2014 HF, RP, JvdM
Problems with Commercialisation
• Costs
– lead to bankruptcy of several developers
• FDA approval
• Legal approval
– no HBOCs approved for use in North America, Australia or
Europe
– Hemopure® has been approved for use in South Africa
• Won’t eliminate need for human blood products
CXA333 Transfusion Science
© UTas SHS 2014 HF, RP, JvdM
Conclusions
• Current
– risks outweigh benefits
– valuable in certain selected applications
• Future (IF successful…)
– may reduce the need for red blood cell transfusions
– but will NOT replace red cell transfusions
– still require other human blood products
– another tool for treatment of at-risk patients
CXA333 Transfusion Science
© UTas SHS 2014 HF, RP, JvdM
References
•
CHANG, T. M. 2012. From artificial red blood cells, oxygen carriers, and oxygen
therapeutics to artificial cells, nanomedicine, and beyond. Artif Cells Blood Substit
Immobil Biotechnol, 40, 197-9.
•
CHEN, J.Y., SCERBO, M. & KRAMER, G. 2009. A review of blood substitutes:
examining the history, clinical trial results, and ethics of hemoglobin-based oxygen
carriers. Clinics, 64, 803-813.
•
HENKEL-HANKE, T. & OLECK, M. 2007. Artificial oxygen carriers: a current review.
AANA journal, 75, 205.
•
MOZZARELLI, A., RONDA, L., FAGGIANO, S., BETTATI, S. & BRUNO, S. 2010.
Haemoglobin-based oxygen carriers: research and reality towards an alternative to
blood transfusions. Blood Transfus, 8 Suppl 3, s59-68.
•
MURPHY, M. F. & PAMPHILION, D. H. 2005. Practical Transfusion Medicine, Oxford,
Blackwell Scientific.
CXA333 Transfusion Science
© UTas SHS 2014 HF, RP, JvdM