Artificial blood components and uses

1. DR ZIKRULLAH
ARTIFICIAL BLOOD

2. Artificial Blood
 Artificial blood or blood surrogate is a substance used to mimic
and fulfil some functions of biological blood,usually in the
oxygen carrying sense.
 Main aim is to provide an alternative to blood transfusion,which
is transferring blood or blood based products from one person to
another.
 It does not contain plasma,RBCs or WBCs.

3. The History of Artificial Blood
 Milk was one of the first substances used as a blood substitute in order to
treat patients with Asiatic cholera.
 After several patients died by receiving milk transfusions, other substances
were discovered as potentials :
• Salt or saline solutions: used primarily as a plasma volume expander,
rather than as artificial blood
• Hemoglobin isolated from red blood cells
• Animal plasma could be used as a substitute for human blood.However,
since many of the materials in animal plasma are toxic to humans, this
posed a problem to using it as a substitute
 The problem of not having a workable substitute led to Ringer’s Solution…

4. Why artificial blood?
 Increasing demand
 Decreasing supply
 Safety
Infectious disease transmission
Transfusion reactions
Immunosuppression
 Cost

5. Ideal Characteristics of Artificial Blood
 Safe to use
 Compatible in the human body
 Able to transport and release oxygen where needed
 Storable and durable for longer time periods
 free of pathogens and toxins
 Viscosity similar to blood
 Low cost

6. Blood Substitute
O2 Carriers
Lack
coagulation
Immune function
Nutrition
Plasma protiens
HB Solutions PFC

7. Perfluorocarbons
 These are chemically and biologically inert,water
insoluble,synthetic aromatic or aliphatic compounds with F
substituted for all H atoms of hydrocarbon.
 water insoluble:so used as emulsion with Puronic-68,egg yolk
phospholipids and triglycerides as emulsifying agent.
 They achieve O2 delivery by using organic chemicals with high
gas solubility.
 The O2 carrying capacity of PFCs is linearly related to PO2 and
obeys Henry’s law.

8.  Short half life(2-4hr):eliminated from body unmetabolised
through the lungs.
 Process of production:
 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
 Perfluorooctyl bromide(oxygent)

9. Perfluorocarbons (PFC) emulsions
Structure:
Perfluorocarbon core Surrounded by a
phospholipid surfactant that reduces the
surface tension of the liquid in which it is
dissolved.

10. PFC
Synthetic organic liquid compounds
8-10 carbon atoms
H+ atoms Halogens
!st Generation
Fluosol 20%
•Stored Frozen
•Limited O2 carrying
capacity.
Allergic reaction
2nd Generation
Oxygent 90%
•Stored at 4’c
•High O2 Carrynig
capacity

11. First generation perfluorocarbon
 FLUOSOL-DA20%-It consists of two PFCs, perfluorodecalin
(PFD) and perfluorotrypropylamine (FTPA) and Pluronic F-68,
as an emulsifying agent, and is able to maintain a balance
between the oxygen carrying capacity and tissue retention.
 It can deliver 0.4ml oxygen per 100ml.

12. Second generation perfluorocarbon
 large oxygen dissolving capacity
 Faster excretion (4 days) and less tissue retention
 Lack of significant side effects
 e.g Perfluorooctyl bromide(Oxygent)
 Bisperfluorobutyl ethylene
 Oxygent can deliver upto 1.3 ml oxygen per 100 ml.

13. Advantages of Perfluorocarbons (PFC) emulsions
 do not react with oxygen
 allow easy transportation of the oxygen to the body
 allow increased solubility of oxygen in plasma
 minimize the effects of factors like pH and temperature in blood
circulation

14. Disadvantages
 causes flu-like symptoms
 unable to remain mixed as aqueous solutions –thus, must be
prepared as emulsions.
 a decrease in blood platelet count.
 PFC products cannot be used by the human body, and must be
discarded.this takes approximately 18-24 months.
 because PFCs absorb oxygen passively, patients must breathe at a
linear rate to ensure oxygenation of tissues.
 Require high FiO2

15. Adverse
Effects
Of PFC
Allergy
Especially 1st Gen
Bleeding
Tendency
Decrease
Plt Count
Increase
Liver
Enzymes
•Acute Rt sided heart
Failure
•Pulmonary edema
•Early: Headache
•Late: Flu like symptoms

16. Hemoglobin-based Oxygen Carriers (HBOCs)
 Hemoglobin-based Oxygen Carriers 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.
 Hemoglobin:a tetramer with two alpha and two beta polypeptide
chains; each is bound to an iron heme group which successively
binds to an oxygen molecule.it has a higher affinity for oxygen,
thus making it an excellent source of blood substitutes.

17. HB
Tetramer
Monomers Dimers
1. Filtered by the kidney
2. NO scavenger
3. Increase plasma osmotic
pressure
4.High O2 affinity
1. Ultrastructural modification
2. Artificial Blood Cells
HB Solutions

18.  To avoid such spontaneous dissociation native Hb is modified by
intramolecular cross-linking between alpha and beta Chains,
polymerization, pyridoxylation, or conjugation to larger
molecules, such as albumin or polyethyleneglycol
("pegylation"),encapsulation of hemoglobin into a liposome or
polymer structure.

19. Cross linking
(diaspirin)
Conjugation
(Albumin,PEG)
Polymerization
Microspheres
(Dendrimer,Polym
ersome)
Recombinant
DNA
technology
Monomers and Dimers
1. Ultrastructural modification
Tetramers
Ultra purification

20. 2. Artificial Blood Cells
Liposomes
=
Pseudoerythrocyte
Nanocapsules
Encapsulated Hb in cell like structure
Coated with
Phospholipid Bilayer
and
Cholesterol
Coated with
Polylactide

21.  PRODUCTION OF HBOCs
 Synthetically produced Hb:E.coli(P678-54)
Isolated Hb:human or animal blood(bovine blood)

22. Current Hb-based oxygen carriers

25. Adverse
Effects
Of Hb
Solutions
Immunsuppression
Decreased
phagocytic activity
Nephrotoxicity
Coagulopathy
Free radicals Vasoconstriction
NO inactivation
Endothelins
Neurotoxicity
Lab Interference

26. Advantages
 Available in much larger quantities
 Can be stored for long durations.
 Can be administered rapidly without typing or cross-matching
 Can be sterilized via pasteurization
Disadvantages
 reduced circulation half-life
 disrupts certain physiological structures, especially the
gastrointestinal tract.
 the release of free radicals into the body

28. 1. Higher O2 Solubility
Coefficient.
2. V. low viscosity
3. High Density
4. High N2 Solubility
5. Inactivate NO
• Resuscitation
•Periop hemodilution
•Organ preservation
•Sickle crisis
•Alveolar recruitment
•Liquid ventilation
•Decompression sickness
•Septic shock

29. Potential clinical applications
 1. Therapeutic
 (a) Blood substitutes : hemorrhagic shock; hemorrhage (war,
 surgery); anaemia.
 (b) Whole-body rinse out : acute drug intoxication; acute hepatic
 failure.
 (c) Local ischemia : acute MI; evolving MI; cardiac failure; brain
 infarction; acute arterial thrombosis and embolism; PTCA of
 coronary artery.
 (d) General ischemia : CO intoxication.

30.  (e) Aid for organ recovery : acute renal failure; acute hepatic
failure;acute pancreatitis.
 (f) Adjuvant therapy : radiotherapy; chemotherapy
 2. Perfusional protection of organs during surgery –
cardiopulmonary bypass
 3. Preservation of donor organ.
 4. Drug carrier - drug-conjugated haemoglobin and
perfluorochemicals.
 5. Contrast agent - (Perfluoro-octylbromide)

31.  Non-Clinical Applications
 1. Culture medium
 2. Chemical examination - oxygen sensor; standard
solution for oxygen calibrator
 3. Bioreactor
 Paradoxical Utilisations (of high-oxygen affinity)
 1. Oxygen absorbent
 2. Oxygen pulse therapy for malignant tumour in
combination with radiotherapy or chemotherapy.

32. Conclusion
 Artificial blood is a good tool for the survival of patients at the
time of surgery when blood loss is higher.
 It carries oxygen to tissues and can support life temporarily until
patients can either regenerate their own red cells or can be
transfused with banked blood.
 It can be sterilised against infectious diseases.
 In short term,the prospective benefits of artificial blood
overshadow the shortcomings.

33. THANK YOU