Artificial blood is an innovative concept of transfusion medicine where specifically designed compounds perform the task of transport and delivery of oxygen in the body to replace this function of allogenic human blood transfusion.
Artificial blood is an innovative concept of transfusion medicine where specifically designed compounds perform the task of transport and delivery of oxygen in the body to replace this function of allogenic human blood transfusion.
Red cell and platelet storage lesions and their effect in transfusion practiseArjuna Samaranayaka
Bio mechanical and metabolic changes that occur in red cell concentrates and platelets during ex-vivo storage, their effect in transfusion practise and strategies to minimize them.
This presentation describes the blood components. It also describes the problems in storing those component and what methods are used to overcome them.
This is my own word presentation of artificial blood ....easy to read n very helpful ...1st try ...this ppt showing the history of artificial blood with the procedure of making of artificial blood also contains advantage disadvantages ..! Please checkout..thank u ...!!
Red cell and platelet storage lesions and their effect in transfusion practiseArjuna Samaranayaka
Bio mechanical and metabolic changes that occur in red cell concentrates and platelets during ex-vivo storage, their effect in transfusion practise and strategies to minimize them.
This presentation describes the blood components. It also describes the problems in storing those component and what methods are used to overcome them.
This is my own word presentation of artificial blood ....easy to read n very helpful ...1st try ...this ppt showing the history of artificial blood with the procedure of making of artificial blood also contains advantage disadvantages ..! Please checkout..thank u ...!!
Blood products topic is very important for Medical students as they have to know which blood product will be much beneficial to patients when they go into clinical practice. This PPT provides all of them.
Provision of ideal transfusion support – The essence of thalassemia careApollo Hospitals
Thalassemia major is a major cause of transfusion dependence among patients world over. Provision of an adequate, uninterrupted and safe blood supply for these patients is the responsibility of the blood services as well as the society as a whole. Thalassemia management has evolved over a period of time and so have transfusion services. Various technological advancements have been introduced in the last few decades in order to enhance blood safety. Adoption of these newer technologies coupled with increasing awareness about voluntary blood donation in the general population can go a long way in improving the life expectancy as well the quality of life in these children.
MISS.SAKSHI S. GOSAVI M.Sc 1 (Biochemistry) NEW ARTS, COMMER...jagtapgovinda1515
What Is Blood Bank?
A blood bank is a center where blood gathered as a result of blood donation is stored and preserved for later use in blood transfusion
The first four papers are part of our ongoing process of publishing research papers in topics related to supply chain management and logistics that raise new research insights. In addition, JOSCM also presents three best papers award nominated in the XX Simpósio de Administração da Produção, Logística e Operações Internacionais (SIMPOI 2017), which occurs annually in Sao Paulo bringing together academic and practitioners in the Operations Management field.
In this new edition of Journal of Operations and Supply Chain Management (JOSCM), the first four papers are part of our ongoing process of publishing research papers in topics related to supply chain management and logistics that raise new research insights. In addition, JOSCM also presents three best papers award nominated in the XX Simpósio de Administração da Produção, Logística e Operações Internacionais (SIMPOI 2017), which occurs annually in Sao Paulo bringing together academic and practitioners in the Operations Management field.
Forensic Existence of Blood as a Dynamic Evidenceijtsrd
Blood is one of the chief form of biological fluid which is recovered at the location of crime. This review article focus on blood as a prime forensic evidence which is most commonly encountered on crime scenes. The font of insipiration for the same is the variable facts and the frequent occurrence of blood as an evidence on the crime scene. The article pronounces the complete details of blood, including its composition, cell types, relation of blood to scientific science, handling liquid blood stains , wet blood stains, dried blood stains, and the post mortum blood and preservation methods followed by a detailed analysis preliminary and confirmatory test . The analysis of blood can be categorised on the basis of its physical and chemical properties. The major aim of this study is to provide all the relevant facts related to blood collection, packaging and the entire examination. Sanya Sharma | Shipra Rohatgi "Forensic Existence of Blood as a Dynamic Evidence" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-3 | Issue-2 , February 2019, URL: https://www.ijtsrd.com/papers/ijtsrd21396.pdf
Paper URL: https://www.ijtsrd.com/biological-science/cell-biology/21396/forensic-existence-of-blood-as-a-dynamic-evidence/sanya-sharma
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Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
5. Blood is circulated in the body through blood vessels by the pumping action of the
heart. With lungs, arterial blood carries oxygen from inhaled air to the tissues of the
body, and venous blood carries carbon dioxide, a waste product of metabolism
produced by cells, from the tissues to the lungs to be exhaled.
WHOLE BLOOD
RED BLOOD CELLS or
Erythrocytes (93%)
WHITE BLOOD
CELLS or Leucocytes
(0.16%)
AGRANULOCYTS
Lymphocytes- 20-40% of white
cells
MonocyteS – 1-10% white cells
GRANULOCYTES
Neutrophils – 50-70% of white cells
Eosinophils ~ 3% of white cells
Basophils ~ 1% of white cells
SOLID FRACTION
(Cells-45%)
PLATELETS or
Thrombocytes (6-7%)
FLUID FRACTION
(Plasma-55%)
5
What is blood?
6. Blood has many functions :
Transportation
Regulation of Body temperature and pH
Protection against blood loss through clotting
Protection against diseases through phagocytic
white blood cells and antibodies
6
7. “Blood is the life” (Riess, 2001)
•When a patient looses too much blood due to trauma
or surgery, the blood volume and RBCs will be reduced
•In such an emergency situation, doctors will often give patients
volume expanders to make up for lost blood volume.
•This helps to restore normal blood pressure and lets the remaining
red blood cells continue to carry oxygen.
•If it is not enough, doctors can give patients blood transfusions to
replace some of the lost blood.
7
Clinical perspective of blood transfusion?
8. Do animals need blood transfusion?
Animals need blood transfusions for the same reasons that
humans do, including surgery, trauma and diseases.
(http://k9bloodbank.com)
8
Usually, the need for blood
transfusions is acute, as in acute
hemorrhage
Transfusions are also appropriate in
treatment of acute or chronic anemias.
Animals with hemostatic disorders
often require repeated transfusions
(Cotter, 2013)
9. What are blood types?
Another protein, an antigen, may be found on some red blood cells - called Rh factor. Blood
cells that have Rh factor are RhD positive, those that don't are RhD negative. 9
10. Animals Blood types
Dogs DEA 1.1, 1.2, 3, 4, 7, and Dal. (DEA system=Dog Erythrocyte antigen
system)
DEA 1.1 negative= Universal Donor
DEA 1.1 positive=Universal Recipient
(Wardrop, 2007)
Cats The main blood group system in cats is the A-B grouping. Cats can be
either type A, type B or type AB.
(http://www.catblooddonors.com/for-cat-owners/about-cat-blood-
transfusions.php)
Cattle The polymorphic systems in cattle include the A, B, C, F, J, L, M, S,
and Z polymorphisms.
(http://en.wikipedia.org/wiki/Blood_type_non-human)
Horses There are eight major recognized blood groups in horses Viz., A, C,
D, K, P, Q, U and T.
( http://en.wikipedia.org/wiki/Blood_type_non-human)
Blood types in animals
11. When transfusion is required, cross matching should be
performed or a universal donor may be used.
Cross-match should be performed in the following situations:
1) Naturally occurring antibodies to foreign blood group
antigens. This occurs in the cat. In this species, a cross-match
should be performed on the first and every transfusion
Type A cats should receive only type A blood and type B cats
should receive only type B blood. However type AB cats can
receive either Type A or Type B blood with minimal or no clinical
reactions
(Henset, 2011)
11
12. 2) Sensitization of an animal to foreign red cell
antigens, in a species without naturally occurring
antibodies. This is the situation in the dog and horse,
resulting in the production of acquired antibodies. In
these species, a cross-match does not need to be
performed on the first transfusion the animal receives
but should be performed at subsequent transfusions.
Also in cow, buffalo, sheep, goat and pig, a single,
unmatched whole blood transfusions are generally safe
(Weiss and Wardrop, 2010)
12
13. 13
Blood collection :
The donor cow restrained in a
head bail and given a small
injection of sedation if needed.
Blood collection takes around
20-30 minutes.
Blood transfusion :
The recipient cow restrained
by halter (and in a head bail if
possible). Blood transfusion
takes around 20 minutes.
http://www.franklinvets.co.nz/Dairy++BeefSheep/Farm+Services/Animal+Health/theileria.html
14. Blood transfusions can be critical, life-saving
procedures.
Blood needs to be readily available—and that
requires a blood bank.
Do animas have blood bank ?
14
15. India's 1st government blood bank for dogs started in Chennai by the
Tamil Nadu Veterinary and Animal Sciences University (TANUVAS)
in 2010.
(http://timesofindia.indiatimes.com/india/Indias-1st-blood-bank-for-dogs-
opens-in-TN/articleshow/5861905.cms) 15
Even in veterinary field, there are several blood
banks which store animal blood for future
transfusion.
Animal Blood Bank
16. 16
Volunteer donor dog during a donation: The dog lies
comfortably on his side and a needle is placed in his
jugular vein to extract the blood. The procedure takes
about 15 to 20 minutes in most dogs.
17. Drawbacks:
According to Riess (2001) blood transfusion carries and will always carry a certain
level of risk.
Blood has to be kept cool (4° C ), and it has a shelf life of 42 days
(Lockwood et al.,2003)
Prolonged RBC storage before transfusion increases multiorgan failure and
mortality in patients (Eldad et al., 2010)
The effects of prolonged storage on red cells include decreased deformability;
depletion of 2,3-diphosphoglycerate (2,3-DPG); increased adhesiveness and
aggregability; reduction in the concentrations of nitric oxide and adenosine
triphosphate etc
(Koch et al., 2008)
17
18. Blood supply shortages :
– A country needs a minimum stock of blood equal to 1 per cent of its
population.
– The total recorded blood collection in India is 4 million units, which meet
only 40% of need against a least requirement of 10 million units.
(World Health Organization, 2008)
Safety of blood supply and risk of infections
– Risk of transmission of HIV, Hep B, Hep C, and other blood borne diseases
– Mistransfusions due to error – Blood Group matching required.
(Scott et al., 1997)
Cost
– Donations, screening, storage, and administration ~ 800-1200 Rs.
(Maiti, 2012)
18
19. The term “artificial blood” is really a misnomer. The
complexity of blood is far too great to allow for
absolute duplication in a laboratory.
(Kresie, 2001)
Artificial blood is a product made to act as a substitute
for blood for the transportation of oxygen throughout the
body.
(Shalini, 2012)
It is also called as Blood Substitute or Arificial Oxygen
Carrier.
19
This is where artificial blood comes in
20. The most promising artificial blood products are
1. Perflourocarbons (PFCs) and
2. Haemoglobin based oxygen carriers (HBOCs).
(Mohankrishna et al., 2011)
The delivery of oxygen by oxygen carriers of the these two
classes of have both benefits and risks which are unique to their
class.
(Tremper et al., 1980)
20
22. In 1616, when William
Harvey first described
the circulation of blood
In 1665, the first
recorded successful
blood transfusion on dog
by Richard Lower
22
(http:// www.redcrossblood.org)
History
23. Many materials used for transfusion that include beer,
urine, milk, plant resins, and sheep blood.
In 1854, patients were injected with milk to treat Asiatic
cholera.
Other materials that were tried during the 1800s include
hemoglobin and animal plasma.
(Chang, 2004)
In 1883,there was a creation of Ringer's solution. In
research using part of a frog's heart, Sydney Ringer,
found that the heart could be kept beating by applying the
solution.
(Hoffman et al., 1990)
23
Contd...
24. In 1909, Karl Landsteiner
classified human blood into four
different groups: A, B, AB, and
O.
A fourth group AB was
discovered the following year.
(Squires, 2002)
Karl Landsteiner
24
Contd...
25. During World War I, galactoso-
gluconic acid was used to extend
plasma.
World War II, human plasma was
used to replace blood and to save
soldiers from hemorrhagic shock.
Eventually, this led to the
establishment of blood banks by the
American Red Cross in 1947.
(Kirschman and Ruth , 2005)
25
Contd...
26. In 1966, experiments with mice suggested a new type of blood
substitute, perfluorocarbons (PFCs).
In 1968, the rat's blood replaced with a PFC emulsion and it
lived for a few hours and recovered fully after blood was
replaced.
(Sarkar, 2008)
However, the established blood bank system in developed
countries worked so well that research on blood substitutes
waned in those countries. It received renewed interest when
the shortcomings of the blood bank system were discovered
during the Vietnam conflict. This prompted some
researchers to begin looking for hemoglobin solutions
(Jani et al., 2012)
26
Contd...
27. Ideal Artificial Blood
Increased availability that would rival that of donated blood, even surpass it
Oxygen carrying capacity, equaling or surpassing that of biological blood
Volume expansion
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
Cost efficient
(Squires, 2002)
27
28. Types of Blood Substitutes
1) Perfluorocarbons (PFCs), chemical compounds which can carry
and release oxygen
2) Haemoglobin-based oxygen carriers (HBOCs) derived from
humans, animals, or artificially via recombinant technology
28(Jani et al.,2012)
30. Perfluorocarbons (PFCs)
Perfluorocarbons are low-molecular-weight linear or cyclic
hydrocarbons in which hydrogen atoms of the carbon chain
have been substituted by fluorine atom, leading to total
chemical inertness and a complete lack of metabolism in
vivo. (Jahr et al., 2007)
1st Generation
Fluosol-DATM
2nd Generation
OxyfluorTM
OxygentTM
30
3rd Generation
PerftoranTM
PHER-O2
TM
32. The PFC particles are about 0.2 microns in diameter
(1/40th of RBC size), with a perfluorocarbon core and a
thin lecithin phospholipids as a coating
(Mohankrishna et al., 2011)
The perfluorocarbons are not hydrosoluble and administered
as emulsions called perfluorocarbon emulsions (PFCEs)
(Squires, 2002)
32
33. Perfluorocarbons do not have the oxygen-bonding properties but act as
simple solvents.
The transport and liberation of gases based on their physical solubility,
and the quantity of gas dissolved linearly related to its partial pressure.
(Jahr et al., 2007)
They Can dissolve more oxygen than the biological blood.
(Cabrales and Intaglietta, 2013)
They carry much less oxygen than hemoglobin-based products
(Jani et al., 2012)
33
Physiology of carrying oxygen
35. Ingredients Quantity (%)
Perfluoro-octyl bromide 28
FO-9982 12
Yolk lecithin 2.4
DSPE-50 H 0.12
Distilled water 57.48
Table 1. Composition of PFC based blood substitute
(Mitsuhiro et al., 2005)
35
Where, DSPE= Distearoyl phosphatidyl
ethanolamine (ammonium salt)
FO =Perfluoroalcohol esters with oleic acid
36. The first generation of PFCEs developed was Fluosol-DATM in 1989.
Fluosol-DATM was approved by US FDA in human, but withdrawn later
because of marginal benefits and development of flu-like symptoms
(Castro and Briceno, 2010)
The second generation of PFCEs developed were OxyfluorTM and
OxygentTM, with improved lipophilicity
(Modery et al., 2013)
36
Developments in PFCEs
37. However, OxyfluorTM was terminated after early clinical
trials due to its severe side effects
OxygentTM was also terminated, because of an increased
incidence of stroke in coronary bypass patients
The third generation PFCEs are PerftoranTM and PHER-O2
TM
Pulmonary complications has been reported with the use of
PerftoranTM and, PHER-O2
TM is in reasearch
(Modery et al., 2013)
37
Contd…
38. Table 2. Current status of PFC based products
Name Sponsor Status
OxygentTM Alliance
pharmaceuticals
(USA)
Discontinued
OxycyteTM Oxygen
biotherapeutics
(USA)
Discontinued
PHER-O 2TM Sanguine Corp
(USA)
In research
PerftoranTM PERFTORAN
(Russia)
Approved in Russian clinical
application.
38
39. Cheap and easy to manufacture in large quantities
Can be stored at room temperature for more than 1 year
Can be mixed safely with any blood group without the need to
check first
The molecules are smaller than red blood cells, allowing them to
bypass arterial blockages and penetrate small capillaries with
ease, delivering oxygen to areas which need it most
Effect of chemotherapy or radiation in tumour treatment can be
enhance when patient pretreated with PFCs
(Jani et al., 2012; Singh et al.,2012)
Benefits of Perfluorocarbon based products
39
40. Adverse
Effects
Of PFC
Allergy
Especially 1st Gen
Repeated doses
may cause hepatic
engorgement
Retained in RE
system
Decrease
platelet count
Impaired neutrophil
function
•Early: Headache
•Late: Flu like
symptoms
(Dietz et al., 1996; Jahr et al., 2007; )
40
42. Understanding Hemoglobin (Hb) :
The structure of Hb was determined in 1959 by Max
Perutz.
Molecular weight 64.5 kDa
Tetrameric protein comprised of two α and two ß-
globin subunits that fold into compact quaternary
structure (α 2 ß 2).
Each α and ß subunit contain an iron-heme group that
binds to oxygen molecule allowing for transport.
42
44. A Hb molecule carries a maximum of four oxygen
molecules.
Various factors such as low pH and high CO2 and high
2,3-diphosphoglycerate (DPG) level in the tissues,
cause a lower oxygen affinity state facilitating oxygen
offloading.
As oxygen is being unloaded, CO2 binds to Hb,
resulting in carbamino-Hb.
44
Contd…
45. Local conditions in the lungs including higher O2,
higher pH, and lower 2,3 DPG level, cause Hb to shift
back to the higher oxygen affinity state.
Such a transition favors CO2 release, which is then
exhaled.
45
Contd…
46. HBOCs
In search for an alternative to PFCs,
considerable efforts have been made in
the development of acellular Hb based
oxygen carriers…
46
47. To prepare acellular Hb, Hb is derived from human or
bovine blood by chemical modifications or from
bacteria host systems by genetic recombinantion
(Alayash, 2014)
Human hemoglobin is obtained from donated blood that
has reached its expiration date
One unit of hemoglobin solution can be produced for every
2 units of discarded blood
(Lesley, 2001)
47
HBOCs (Hemoglobin-based oxygen carriers)
Once obtained from any of these sources, the
hemoglobin must be purified and modified to decrease
its toxicity and increase its effectiveness
48. • The first clinical study with free hemoglobin resulted in
nephrotoxicites. The hemoglobin used was found to
have erythrocyte membrane stromal lipids as well as
bacterial endotoxins.
(Shalini, 2012)
• To side-step these problems, stroma-free hemoglobin was
developed, but new problems arose,
o 1) too short intravascular half life
o 2) too high affinity for oxygen
(Jean, 2001)
48
49. 1) Stroma free Hb had too short of an intravascular half life
because tetrameric Hb (α 2 ß 2) dissociated into αß
dimmers that were filtered by the kidneys and excreted in
the urine.
2) Stroma free Hb had too high of an oxygen affinity because
2,3-DPG was lost during the purification process.
(Shalini, 2012)
To increase the intravenous half life of hemoglobin solutions,
manufacturers had to develop methods to stabilize the
hemoglobin tetrameric structure and increase its size.
Additional modifications in the hemoglobin, such as
pyridoxylation, will create a product with near-normal
oxygen-binding affinity.
(Lesley, 2001)
49
51. (A,B) Tetrameric stabilization by intramolecular
crosslinking between the two α or ß
(C) The effective molecular weight of Hb can be
increased by conjugating it to polyethylene glycol.
(D) Polymerized Hb may be produced through
polyfunctional crosslinking agents.
E) Hb can also be encapsulated into liposomes
51
52. Intramolecular cross-linking
Because the alpha/beta (α-ß) dimers are relatively stable,
the goal of intramolecular modification is to cross-link the
two alpha (α-α) or beta (ß-ß) subunits and stabilize the
association of the two alpha/beta (α-ß) dimers.
The popular cross-linkers used are 3,5-dibromosalicyl
fumarate (DBBF) and nor-2-formylpyridoxal 5-phosphate
(NFPLP).
(Mohankrishna et al., 2011)
The cross-linking not only prevents tetramer dissociation,
but also reduces the affinity of Hb for O2.
52
53. Addition of 2,3 DPG analogs such as pyridoxal-5’-phospoate can fix the
too high oxygen affinity of stroma-free hemoglobin.
The more DPG in the cell the more oxygen delivered to the tissue. The
less DPG; the less oxygen delivered to tissues.
Pridoxylated stroma-free hemoglobin has nearly normal oxygen affinity
(p50 = 22-24 mmHg)
(Jean, 2001)
E.g., HemopureTM (Hemoglobin Glutamer-250 (bovine) or HBOC
201)
53
54. Polymerized Hemoglobin
Polymerization of Hb through intermolecular cross-
linking increases the size of molecules through the
formation of Hb oligomers. In the process multiple Hb
proteins are linked together through the use of
dialdehydes, such as glutaraldehyde and glycoaldeyde.
(Betts and Whittet, 1962)
E.g., PolyHemeTM
54
55. Conjugated Hemoglobin
Conjugation of Hb is the binding of Hb to a biocompatible
polymer, such as polysaccharide, in order to increase its overall
size.
In a specific case of pegylation, multiple polyethylene glycol
(PEG) chains are added to the Hb protein as a means to
increasing the molecule's size.
55(Mohankrishna et al., 2011; Shalini, 2012)
56. 56
Size increases from 3 nm to 15 nm once pegylated
Hb conjugation with PEG appears to protect the
molecule from renal excretion.
Conjugating Hb with a macromolecule extends the
intravascular circulation time of a HBOC.
E.g. HemospanTM
(Shalini, 2012)
57. Hemoglobin Vesicles (Hemoglobin
encapsulated vesicles)
The encapsulation of Hb is based on the
idea of recreating the natural properties
of RBC without the presence of blood
group antigens
Encapsulated Hb is often referred to as
―hemosome
The process of involves the encapsulation of Hb within lipid vesicles
using a solution of phospholipids.
Lipid membrane allow better diffusion of O2 and Co2
57
(Shalini, 2012)
58. Recombinant Hemoglobin
With advances in recombinant DNA technologies,
specially modified Hb may be produce from
microorganisms, like E. coli
Recombinant human hemoglobin was produced in E.
coli using an expression vector containing two mutant
human globin genes. One was a low oxygen affinity
mutant, and the other fused α-globins.
These recombinant hemoglobin products advanced to
clinical trials, but it was stopped due to
vasoconstriction and other harmful effects.
58
(Mohankrishna et al., 2012)
59. Table 3. HBOC Products
Name Sponsor
Description
HemopureTM Biopure Corp
It is made of chemically stabilized, cross-linked bovine haemoglobin in a salt
solution. Hemopure is approved for Phase III trials in the United States and
South Africa (Stefan et al., 2007)
OxyglobinTM Biopure Corp
It consists of chemically stabilized bovine haemoglobin in a balanced salt
solution. Oxyglobin is aproved by US FDA and European Commission for
veterinary use particularly for routine use in canine anaemia (Jahr et.al.,2007)
PolyHemeTM Northfield
Laboratories
human hemoglobin-based oxygen- carrying blood but discontinued due to
adverse effects.
HemospanTM Sangart
It was produced in powder form, which could then be mixed into liquid form
and transfused immediately but discontinued due to adverse effects
HemotechTM HemoBiotech
Hemotech is currently approved for Phase I trials.
59
61. Characteristics Biopure’s Oxygen
Therapeutics
Red Blood Cells
Storage Room temperature (2o to
30o C)
Refrigerated
Shelf life 36 months 42 days
Preparation Ready to use Testing, typing and
crossmatching
Compatibility Universal Type specific
Effectiveness Immediate oxygen delivery Dependent on length of
storage
Purity Processed to remove
infectious agents
Tested and screened for
infectious agents
Raw material Bovine haemoglobin Human Blood
Cost $ 600 - 800 $ 125 - 425
(http://biomed.brown.edu)
61
Table 4. Biopure’s Oxygen Therapeutics vs. RBC’s
62. Table 5. Current developmental status of HBOCs
Product type Product name Developer Source and /or
technology
Status
Cross-linked Hb HemAssist
TM
Baxter (USA) αα cross-linked
human Hb
Discontinued
Optro (rHb)
TM
Somatogen (USA) Recombinant Hb Discontinued
Polymerized Hb PolyHeme
TM
Northfield Lab
(USA)
Glutaraldehyde,
pyridoxal human
Hb
Discontinued
Hemopure
TM
Biopure (USA) Glutaraldehyde
bovine Hb
Approved *
Conjugated Hb Hemospan
TM
Sangart (USA) Maleimide PEG-
human Hb
Discontinued
PEG-Hb
TM
Enzon (USA) PEG conjugated
bovine Hb
Discontinued
PHP
TM
Apex (USA) Polyoxyethylene-
conjugated human
Hb
Discontinued
* Approved in South Africa for perioperative anemia; approved in USA and Europe
for veterinary use under the name ‘Oxyglobin’.
(Tao and Ghoroghchian, 2014)62
63. Benefits
of
HBOCs
No prior
planning
Faster &
better O2
distribution
Long shelf
life
No
refrigeration
Universally
compatible
Immediately
offloads
oxygen
Ready to use
(Mohankrishna et al., 2011;
Singh et al., 2012)63
64. Side effects
of HBOCs
Vasoactivity/
hypertension
Gastrointestinal
side effects
Pancreatic
and liver
enzyme
elevation
Antigenicity
Cardiac
involvement
Platelet
aggregation
Neurotoxicity
Renal effects
(Cole et al., 1997; Mohankrishna et al., 2011;
Singh et al., 2012; Winslow , 2004) 64
65. Advantages of Artificial blood
No risk of infection
Biological blood transfusion is the second largest source of
HIV infections in Nigeria. In certain regions of southern
Africa, it is believed that as much as 40% of the population
has HIV/AIDS. A disease-free source of blood
substitutes would be incredibly beneficial in these region
(Shalini, 2012)
Can be kept at room temperature and carry a shelf life of
more than 1 year
Rapid treatment of patients in trauma situations
Medical care in the armed services would get benefit from
artificial blood
65
66. Artificial blood allows for immediate full capacity oxygen
transport
(Schimmeyer, 2002)
An alternative for those patients that refuse blood transfusions
for religious or cultural reasons.
(Jani et al., 2012)
Synthetic oxygen carriers may also show potential for cancer
treatment, as their reduced size allows them to diffuse more
effectively through poorly vasculated tumour tissue, increasing
the effectiveness of treatments like photodynamic therapy and
chemotherapy.
(Won, 2005)
Transfused blood is currently more cost effective, but there are
reasons to believe this may change. For example, the cost of
artificial blood may fall as manufacturing becomes refined.
66
Contd…
67. There is a possibility of using stem cells as a means of
producing an alternate source of transfusable blood.
A study performed by Giarratana et al. (2013) describes a large
scale ex-vivo production of mature human blood cells using
hematopoietic stem cells.
A team of IIT-Madras scientists from the department of
engineering design has been successful in creating enough red
blood cells from stem cells.
(Narayan, 2013)
To date, the use of red blood cells (RBCs) produced from stem
cells in vitro has not proved for routine transfusion.
(Kim, 2014)
67
Other Promising Technique
68. Artificial blood controversy
• Doctors abandoned the use of HemAssistTM in the United States,
after patients who received the HBOC died more often than those
who received donated blood.
• Haemoglobin-based blood substitutes may increase the odds of
deaths and heart attacks.
• Sometimes, pharmaceutical companies may get trouble in proving
that their oxygen carriers are effective, i.e. Northfield Laboratories
• Blood substitutes may be misused as performance-enhancing
drugs.
(Shalini, 2012)
68
69. • Blood supply demand are increasing as compared to blood
donations in the world.
• Artificial blood is especially useful in circumstances when
donor RBC units are unavailable or when transfusion of
real blood is not an acceptable option.
• Two distinctly different classes of oxygen carriers are being
developed, each capable of transporting and delivering
oxygen to peripheral tissues.
• Most of the initial attempts at synthesizing blood
substitutes were not favorable because of significant
adverse effects.
69
Conclusion
70. However, Considering the need, there are several
companies still working on the production of a safe and
effective artificial blood substitute.
Though, there are many challenges in this aspect,
advancing science and technology may result in
development of better blood substitutes in future for
overcoming the need for biological blood transfusions
in the operative and trauma settings.
70
Contd…
Perfluorocarbons are low-molecular-weight linear or
cyclic hydrocarbons in which hydrogen atoms of the
carbon chain have been substituted by fluoride, leading
to total chemical inertness and a complete lack of metabolism
in vivo. They have a high solubility coefficient for
oxygen, higher than the coefficient for oxygen dissolved
in plasma oxygen