2. INTRODUCTION
● Blood is a body fluid in humans and other animals that delivers
necessary substances such as nutrients and oxygen to
the cells and transports metabolic waste products away from
those same cells.
● It is composed of blood cells suspended in blood plasma.
Plasma, which constitutes 55% of blood fluid, is mostly water
(92% by volume), and contains proteins, glucose,
mineral, ions, hormones, carbon dioxide and blood cells
themselves
5. Artificial blood
● Artificial Blood (also called Blood Substitute or Blood Surrogate)
is a substance used to mimic and fulfill 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.
● It does not contain plasma , RBCs or WBCs.
6. Need for artificial blood
● Natural blood must be stored at a cool temperature and it has a
short shelf life of only 42 days.
● Shortage of blood
● Immunological incompatibility
● Rare blood group demand
● Disease Transmission
● cost
7. Advantages of Artificial Blood
● Safe to use
● Compatible in the body- elimination of cross matching
● Oxygen carrying capacity, equally or surpassing that of
biological blood
● Pathogen and toxin free
● Minimal side effects
● Long shelf life
● Survivability over a wider range of storage temperatures
● Viscosity similar to Body blood
● No immunosuppression
● Cost efficient
8. BLOOD SUBSTITUENTS
● Blood substituents can serve as :-
○ Plasma volume expander
○ Replicate the oxygen carrying function of natural blood
● Plasma Expanders :- These are compounds, which are either entirely
synthetic or processed from natural proteins that serve as infusion
solutions which expand intravascular volume.
● RBC Substituents :- these are oxygen carriers but, differ the
way they carry .They are:-
○ Modified Hemoglobin
○ Perflurocarbons
9. PLATELET SUBSTITUENTS
● Platelet substituents have following properties:-
Effective hemostasis with a significant duration of action
No associated thrombogenicity
No immunogenicity
Sterility
Long shelf life with simple storage requirements
Easy preparation and administration
● Several different forms of platelet substitute are now under
development :
Infusible Platelet Membranes (IPM)
Thrombospheres
lyophilized human platelets
11. RED BLOOD CELL SUBSTITUENTS
● Main function is to carry oxygen, as does natural hemoglobin.
● The use of oxygen-carrying blood substitutes is often called
Oxygen therapeutics to differentiate from true blood substitutes.
● The initial goal of oxygen carrying blood substitutes is merely to
mimic blood's oxygen transport capacity.
● There are two basic approaches to constructing an oxygen
therapeutics:
○ The first is perfluorocarbons (PFC), chemical compounds which
can carry and release oxygen. The specific PFC usually used is
either perfluorodecalin or dodecafluoropentane emulsion
(DDFPe).
○ The second approach is hemoglobin(HBOCs)
derived from humans, animals, or artificially via
recombinant technology, or via stem cell
production of red blood cells in vitro
13. PERFLUOROCARBONS
● 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 materials.
● 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.
● They have the ability to carry much less oxygen than
haemoglobin based products.
14. STRUCTURE
● Perfluorocarbon core Surrounded by a phospholipid
surfactant that reduces the surface tension of the liquid in
which it is dissolved.
15. PRODUCTION PROCESS :-
● Water, salts, and phospholipids surfactant,
antibiotics,vitamins,nutrients are added and emulsified through
high-pressure homogenization.
● Purified through high temperatures of steam.
● Common PFCs:
○ Perfluorodecalin
○ Perfluoro octyl bromide(oxygent)
16. Generations of PFC
● 1st generation
○ FLUOSOL- DA 20%
○ Stored Frozen
○ Limited O2 carrying capacity.
○ Allergic reaction
○ It can deliver 0.4ml oxygen per 100ml blood
● 2nd generation
○ Oxygent 90%
○ Stored at 4’c
○ High O2 Carrying capacity
○ Oxygent can deliver upto 1.3 ml oxygen per
100 ml blood.
17. EXAMPLES OF PFC
● Fluosol-DA-20
Fluosol-DA-20, manufactured by Green Cross of Japan, was the
first and only oxygen-carrying blood substitute ever to receive
approval from the FDA. Although approved in 1989, it was withdrawn
in 1994 because it was cumbersome to administer to patients and it
had side effects.
● Oxygent
Oxygent, developed by Alliance Pharmaceutical Corporation in
San Diego, is a PFC-based oxygen carrier currently approved for
Phase II trials in both Europe and the United States. Oxygent initially
showed promise for decreasing the need for donated blood during
surgery. However, phase III trials were stopped recently because
patients receiving Oxygent showed a higher risk of
stroke compared to controls receiving donor blood.
18. ● Perftoran
Perftoran, sponsored by Moscow, Russia, is a PFC emulsion
approved for human use in Russia in 1996. In 2005, the same drug
was registered and approved as an authorized blood substitute for
use in Mexico under the trade name Perftec, distributed by KEM
Laboratory in Mexico.
● PHER-O2
PHER-O2, developed by Sanguine Corporation in Pasadena, CA,
is a PFC with oxygen-carrying capabilities and reportedly few side
effects. This drug is now under evaluation not only as a blood
substitute for transfusion, but also as a therapy for heart attack and
stroke.
20. Advantage of PFC
● Do not react with oxygen
● Inexpensive
● 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
blood circulation.
21. Disadvantages of PFC
● Often causes flu-like symptoms
● Unable to remain mixed as aqueous solutions
● 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
22. HAEMOGLOBIN BASED OXYGEN CARRIERS
● Hemoglobin-based Oxygen Carriers(HBOC) were created as a
mechanism to mimic the oxygen-carrying role of hemoglobin in
the body, while still reducing the need for real human
hemoglobin.
● HBOCs are manufactured from sterilized hemoglobin and look
somewhat like real blood.
● These dark red colored blood substitutes are often made from
RBCs of expired human blood, cow blood, hemoglobin-
producing genetically modified bacteria, or human placentas.
● Through a chemical process called polymerization, two or more
three molecules bonded together to form a larger
HBOC molecule.
23. ● HBOCs are smaller than natural RBCs. While natural
RBCs remain in the bloodstream for about 100 days,
HBOCs circulate in human blood for only a day.
● SIDE EFFECTS OF HBOC
elevated blood pressure,
abdominal discomfort,
a temporary reddish coloration of the eyes or skin.
24.
25. PRODUCTION PROCESS
● HB synthesis
○ Synthetically produced Hb: E.coli(P678-54)
○ Isolated Hb: human or animal blood(bovine blood)
● Seed Tank
● Fermentation
● Final processing
27. ● PolyHeme
○ PolyHeme, sponsored by Northfield Laboratories in Chicago, is a
first-generation polymerized hemoglobin-based oxygen-carrying
hemoglobin solution. In the mid-2000s Polyheme was compared
with donor blood in a clinical trial of more than 700 people in a US
Phase III Trial.
○ Patients receiving Polyheme had a slightly higher rate of negative
side effects such as high blood pressure, inflammation, and
multiple organ failure compared with the control group. (The small
size of the PolyHeme molecule causes it to bind with nitric oxide,
leading to constricted blood vessels).
28. ● Hemotech
○ Hemotech, produced by HemoBiotech in Dallas, TX, is
a proprietary, chemically modified hemoglobin
manufactured from cow blood. It was originally
developed in 1985. With a shelf life of more than six
months, if has shown no signs of toxicity in clinical
studies. Hemotech is currently approved by the FDA
for Phase I trials in the United States.
29. Advantage of HBOC
● 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.
30. Disadvantage of HBOC
● Short half-life
● Disrupts certain physiological structures, especially the
gastrointestinal tract and normal red blood cell
haemoglobin.
● They release free radicals into the body
● Availability and cost
31. APPLICATIONS OF ARTIFICIAL BLOOD
● Blood substitutes :
○ hemorrhagic shock; hemorrhage (war, surgery); anemia.
○ Whole-body rinse out : acute drug intoxication; acute hepatic
failure.
○ Local Ischemia : acute Myocardial infection ; cardiac failure;
○ brain infarction; acute arterial thrombosis and embolism.
○ General Ischemia : CO intoxication.
○ Aid for organ recovery : acute renal failure; acute hepatic failure ;
acute pancreatitis.
○ radiotherapy; chemotherapy.
