ABSTRACT:
Blood
transfusion was once regarded as a safe and effective practice to save a
patient’s life after massive blood loss. But the AIDS epidemic and concerns
that donated blood could be contaminated with HIV and other infectious agents,
such as the hepatitis C virus, shattered public confidence in blood
transfusions. This only added to already existing supply problem that normal
blood lasts for less than 42 days only. Artificial blood is a product made to
act as a substitute for red blood cells. While true blood serves many different
functions, artificial blood is designed for the sole purpose of transporting
oxygen and carbon dioxide throughout the body. Depending on the type of
artificial blood, it can be produced in different ways using synthetic production,
chemical isolation, or recombinant biochemical technology. Various
manufacturers have products in clinical trials; However, no truly safe and
effective artificial blood product is currently marketed.
INTRODUCTION:
There
has been a need for blood replacements for as long as patients have been
bleeding to death because of a serious injury. According to medical folklore,
the ancient Incas were responsible for the first recorded blood transfusions.
No real progress was made in the development of a blood substitute until 1616.
In the years to follow, medical practitioners tried numerous substances such as
beer, urine, milk, plant resins, and sheep blood as a substitute for blood. The
first successful human blood transfusions were done in 1667. Unfortunately, the
practice was halted because patients who received subsequent transfusions died.
William Amberson
and colleagues at the State College of Medicine in Memphis showed that bovine haemolysates could transport oxygen in mammals , and
later found that human haemolysates had the same potential when infused in
patients . Since then, the development of transfusion medicine has received
much of its impetus from the military—not surprising, given that haemorrhage
is the leading cause of death on the battlefield.
IDEAL
PROPERTIES:
In
early stages it is clear that it was not neccessary to develop a substance that mimics all
the functions of whole blood. But rather a temporary oxygen carrier to provide
adequate oxygen perfusion & Carbon dioxide removal under physiological
conditions. Wartime experience guided developers in delineating the ideal
properties of an oxygen carrier for military use:
üUniversal
compatibility, and thus no time-consuming testing for blood type;
üNo
transmittable pathogens or allergens;
üLong-term
storage capability, preferably under non-refrigerated conditions;
üSafety
and non-toxicity; and
üSuperior
oxygen delivery capability, resulting in oxygenation of peripheral tissues even
after massive blood loss.
DISCUSSION:
The
first obvious candidate was haemoglobin (Hb), the oxygen-carrying molecule
itself, but was noted serious complications with this approach, including vasoconstriction, abdominal pain and acute
kidney failure. Indeed, Hb is toxic per
se, because outside a red blood cell, its
tetrameric structure is rapidly broken down into dimers and monomers that are
taken up by the kidney where they impair nephrological functions. Given these
problems with pure Hb, two main strategies for the development of blood
substitutes have emerged: oxygen carriers that are based on modified Hb; and
perfluorocarbon (PFC)-based products.
Hb
Based Oxygen Carriers :
Main stay of research concentration is laid on HBOCs as Hb can be obtained
easily in sufficient quantity. The real challenge is how to control the
negative side effects of the protein. Various researchers have therefore tried
to stabilize the Hb tetramer by using recombinant techniques or chemical
crosslinkers and have added 2,3- DPG analogues to reconstitute the normal
oxygen affinity of Hb along with polymerization .
Products
:
a.PolyHeme®, a glutaraldehyde polymerized human Hb
developed by Northfield Laboratories ,is now being tested in a phase III trial
for early treatment of trauma patients.
b.Hemospan™, is a non-polymerized human Hb molecule
with its surface modified by polyethylene glycol (PEG) which is anticipated to
enter phase III trials early next year.
c.Other
artificial RBCs 2nd
Generation – PolyHb with
superoxide dismutase and catalase enzyme.
d.3rd Generation – Hb in lipid vesicles &
biodegradable polymeric membrane- nanoartificial RBCs. PFCs :
The
main alternative to Hb-based solutions are PFCs, which are hydrocarbon like
substances with fluorine instead of hydrogen atoms. Unlike Hb, gas molecules are not
chemically bound to PFCs, but are absorbed and released by simple diffusion.
They are insoluble in water and must be emulsified before infusion, and they
are rapidly removed from circulation and sequestered in the reticuloendothelial
system, where they can cause complications. Furthermore, the oxygen carrying
capacity of PFCs depends on the oxygen partial pressure to which the solution
is exposed, which also limits their use to situations with supplemental oxygen
and controlled ventilation.
Products
:
a.Fluosol® : The only oxygen carrier approved so
far by the FDA is a PFC emulsion, developed by Green Cross Corporation in
Japan.
b.OxygentTM : a new PFC emulsion, , designed to
overcome the problems that eventually caused the FDA to pull Fluosol
from the market. Oxygent is intended to reduce the need for donor
blood during surgery; it has already completed a phase III clinical study.
USES:
§Haemorrhage
,
§Traumatic wounds
§Auto-immune hemolysis ,
§Air embolism ,
§Haemolytic
shock
§Sickle cell anemia
§Thalasemmia
,
§Organ preservation
CONCLUSION
Whether
the Hb- or PFC-based products under trial are eventually approved for clinical
or battlefield use remains to be seen. Substituting blood is a complex process
and even the latest products may need further refinement to overcome various
side effects. “Each new generation of red blood cell substitutes is
increasingly more complicated and expensive,”
Nevertheless, given the great demand for
artificial blood substitutes and the increasing interest from academic
researchers and biomedical companies are positive that future products will be
safe enough for widespread use in surgical theatres and in the field, to rescue
people after massive trauma.
REFERENCES
a)Chang, TMS. Artificial cells:
biotechnology, nanotechnology, blood substitutes, regenerative medicine, bioencapsulation, cell/stem cell therapy. Singapore:
World Science Publisher; 2007. p.452
b)EUROPEAN MOLECULAR BIOLOGY ORGANIZATION EMBO reports VOL 6 | NO 8 | 2005 pg no.705
