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Major functions of blood
Maintenance of normal
acid base balance in the
Regulation of body
temperature by the
distribution of body heat
Regulation of water
balance through the
effects of blood on the
exchange of water
between the circulating
fluid and the tissue fluid
Defence against infection
Transport of hormones
and regulation of
Transport of metabolites
A blood substitute is a substance used to mimic and fulfil
some functions of biological blood.
It aims to provide an alternative to blood transfusion,
which is transferring blood or blood-based products from
one person into another.
The number of blood donations needed by India every day!
• 4 Crore
No. of units- every year our nation requires out of which
only a meagre 40 Lakh units of blood are available
• 1 million
New people are diagnosed with cancer each year
% people in the eligible population of India donates blood
Need for blood substitute
Shortage: A very important limitation especially during
disasters, wars, emergencies, when it is needed most.
Short shelf life: This leads to a large amount of wastage of
Rare blood groups: This can be a problem, especially in under
populated areas or in a situation where there is a large
demand for blood.
Disease transmission: HIV, HBV, HCV to name some of the
most common pathogens.
1667 - Jean-Baptiste Denys performed the 1st documented
blood transfusion on a 15 yrs. anemic boy with sheep
pt. survived, but subsequent transfusions with sheep blood
1900’s – WWII and Vietnam war ignited the search for
blood substitutes - hemoglobin solutions and synthetic O2
1980’s – the search for alternative blood substitutes further
fueled by the discovery of HIV and Hep C being transmitted
Ideal blood substitute
Oxygen carrying capacity, equalling or surpassing that of
Universal compatibility: elimination of cross matching
Pathogen free: elimination of blood contained infections
Minimal side effects
Survivability over a wider range of storage temperatures
Long shelf life
Types of blood substitute:
Can serve as
– Plasma volume expanders or
– Replicate the oxygen carrying function of natural blood
1. Plasma Expanders: These are compounds, which are either
entirely synthetic or processed from natural proteins that serve
as infusion solutions which expand intravascular volume.
2. RBC Substitutes:
Modified Haemoglobins - these are essentially human
haemoglobins extracted from outdated blood.
Perflurocarbons - Synthetic organic compounds that can take
normal saline, dextrose and
Can serve as volume
substitutes and maintain
encompass a wide range of
These compounds hold
water and actually expand
volume over the amount
These are modified gelatin polymers, which were among the
earliest used colloid expanders, but are now being phased out
due to an inherent risk of anaphylaxis.
This is a newer generation of colloid expander which uniquely
not only expands plasma volume, but also serves to decrease
blood viscosity, thereby improving perfusion.
Hydroxyethyl Starch (HES):
This is a polymerized form of plant starch which is structurally
similar to glycogen and is therefore the safest of the plasma
Albumins and Purified Protein Derivatives:
These are prepared by fractionating albumin and other proteins
from pooled human blood and then sterilizing and processing
the albumin so that it is iso-osmolar with plasma. These carry the
greatest risk of anaphylaxis.
Uses of plasma expanders
Both crystalloids and colloids have a specific role in overall
management of hypovolemia & are life saving products for
acute emergency situations requiring resuscitation.
They are usually used prior to blood transfusion, because
no processing or testing of the patient is required for
transfusion of expanders and hence can be infused
Dextrans are currently enjoying a large share of research
focus due to potential applications, related to their ability
to coat blood cells and prevent thrombus formation.
This makes them particularly useful in vascular surgery,
such as intravascular stent placement or surgery for DVT.
Also, coating of erythrocytes causes mutual repulsion
between erythrocytes, and this improves
This property has led to investigations of a potential role
for dextrans in plastic surgery to improve perfusion and
thereby hasten healing of skin grafts.
Anaplylaxis: This remains the chief drawback with plasma
expanders. It is particularly prevalent with gelatins and albumins
while HES and Dextrans have a very low reported incidence.
Disease transmission: The incidence of transmission of disease is
negligible when compared with blood, but cases have been
Nephrotoxicity: It is reported especially with dextrans.
Volume overload and electrolyte imbalance: Can be prevented by
careful titration of transfused amount and monitoring.
PFC based blood substitutesFC)
PFC are biologically inert
materials that can dissolve
about 50 times more oxygen
than blood plasma.
They are relatively inexpensive
to produce and can be made
devoid of any biological
Emulsion particles are 0.2
micron in diameter → Can
perfuse smallest capillaries,
where no RBC flow.
Not soluble in water, which means to get them to work
they must be combined with emulsions.
Now a day’s most of the PFBOCs are mixtures of
perfluorocarbons with emulsifying agent
They have the ability to carry much less oxygen than
haemoglobin based products.
This means that significantly more PFC must be used.
One product of this type has been approved for use by
FDA, but it has not been commercially successful because
the amount needed to provide a benefit is too high.
Advantages of PFC emulsions
Do not react with oxygen.
Allow easy transportation of the oxygen to the body.
They allow increased solubility of oxygen in plasma.
minimize the effects of factors like pH and temperature in
Disadvantages of perfluorocarbons (PFC)
Often causes flu-like symptoms.
Unable to remain mixed as aqueous solutions – thus, they
must be prepared as emulsions for use in patients.
A decrease in blood platelet count.
PFC products cannot be used by the human body, and
must be discarded.
PFCs absorb oxygen passively, patients must breathe at a
linear rate to ensure oxygenation of tissues.
The problem with Fluosal-DA was that they dissolve less
oxygen than pure liquids.
Examples of PFC based products
Oxygent Currently approved for Phase II Trials in US and Europe,
developed to ↓ need for donor blood during surgery.
Done well overall in most clinical trials, but recently, a
cardiac surgery study found participants to be slightly
more likely to suffer if treated with Oxygent rather than
by standard care.
Oxycyte Currently approved for Phase II-b Trials in the US.
Targeted as an oxygen therapeutic, with successful
small scale open label human trials treating traumatic
PHER-O2 In research
Perftoran Approved in Russian and Mexico. Distributed by KEM
Its infusion alleviates symptoms of ischemia at different
types of occlusion vessels disease, improves grafting in
plastic surgery, diminishes inflammation and prevents
rejection of transplants, inhibits retro-virus infection
Local Perftoran applications are able to accelerate wounds
and ulcers healing.
withdrawn in 1994 due to usage complexity, limited
clinical benefit and complications
SMACC Gold 14
Advantages of HBOCBOCS)-
Available in much larger quantities.
Can be stored for long durations.
Can be administered rapidly without typing or cross
matching blood types.
Can be sterilized via pasteurization.
Disadvantages of HBOCRS (HBOCS)
Disrupts certain physiological structures, especially the
gastrointestinal tract and normal red blood cell
They release free radicals into the body
Availability and cost
SMACC Gold 14
Examples of HBOCs
Currently approved for Phase III trials in US and was more
widely approved in South Africa. Many safety measures
are taken to render free of pathogens, including herd
control and monitoring.
Oxyglobin Currently approved for veterinary use in US & Europe.
Oxyglobin solution is the first & only oxygen
therapeutic to be both US FDA and European Commission
approved for veterinary use. Oxyglobin has been used
primarily for blood transfusions and for treatment of
anaemia in dogs.
Unique human HBOC in development for the treatment
of urgent, large volume blood loss in trauma and surgical
settings. It is the only blood substitute that has
completed a Phase III trial. Also, free haemoglobin
can be taken up by the kidney, causing dysfunction and
failure, similar to a hemolytic transfusion reaction
Phase II trials completed.
Hemospan is currently in Phase II trials in the US. It is
produced in powder form, which can then be mixed
into liquid form and transfused immediately, regardless
of a patient’s blood type. This technology relies on
coupling with polyethylene glycol (PEG) to eliminate
the toxicity associated with free haemoglobin.
Phase 3 trials completed. Abandoned due to cardiac
Safety of HBOCs
1980 – 2008
Lumbricus terrestris (earthworm) erythrocruorin (LtEc)
A naturally occurring extracellular
Hb with high molecular weight
(3.6 MDa), low autoxidation rate,
and limited NO dioxygenation
These properties make LtEc a
potential candidate for use as RBC
Can be safely transfused into
mice, rats, and hamsters without
eliciting major side effects.
A novel blood substitute that is an oxygen carrier with
Formed by crosslinking fibrinogen to hemoglobin to form
In the in vitro experiments, PolyHb-Fg showed similar
clotting times as whole blood, whereas polyHb showed
significantly higher clotting times.
Hemopure, as with any oxygen carrying
therapeutic, carries a risk of being used
improperly as a performance
enhancement in sports.
on July 20, 2007, Michael
Rasmussen was accused by mountain
bike racer Whitney Richards of
attempted Hemopure smuggling for
potential later use in a doping
Infusible platelet membranes
Red cells with surface-bound fibrinogen
Blood products grown from stem cells
RBCs may be grown either from embryonic stem cells or
hematopoietic progenitor cells.
in 2008, Lu et al reported success using embryonic stem
cells to grow mature erythrocytes on a large scale.
However, the cells produced show a phenotype more
consistent with fetal or embryonic erythrocytes than
adult blood cells.
Further research will be required to increase yields,
eliminate potentially tumorigenic nucleated cells, and
determine the half-life and immunogenicity of
erythrocytes grown from stem cells.
Other potential techniques
Compromises of fluorocarbon
and hydrophilic moieties.
Compatibility with plasma is
due to discrete well‐defined
globular shapes, flexibility,
chemical stability low
cytotoxicity and hydrophilicity
of exterior makes it a major
step forward in the field of
blood substitutes e.g. Poly
To enhance circulation times,
recombinant or polymerized
haemoglobin can be encapsulated
amphiphilic block copolymers
The hydrophobic core of polymer
micelle is able to solubilize the
similarly hydrophobic Hb protein,
while the water soluble corona
(polyethylene glycol) provides a
steric barrier to protein
absorption, and provides
protection from clearance by RES.
Placental umbilical cord blood
Cord blood collected aseptically from
the placenta after the birth of a healthy
baby can be used safely as a blood
higher haemoglobin content and
growth factors than normal blood from
an adult, which has the potential to
benefit patients in varying diseases.
Are hypothetical, microscopic, artificial
red blood cells that can emulate the
function of its organic counterpart with
A team of Romanian researchers
announced that they discovered a colorless
substance that can replace blood. The
substance is based on hemerythrin
,extracted from sea worms and it was
tested on mice with encouraging results.
October 31, 2013
1. Not featuring a superoxide ligand (unlike Hb), which
drastically reduces the reactivity towards NO, and
2. Exhibiting stability towards peroxide (unlike Hb).
The more you sweat in peace, the
less you bleed in war.