Abstract
Blood transfusion has turned to be safe and
practical since the 90s but there are still many challenges that face the
process and need development and improvement. There is need for industrial RBC
rising from medical emergencies to genetic hemolytic disorders. This includes
many diseases and health problems. Many viruses such as hepatitis viruses as
well as human immunodeficiency viruses are able to be transmitted by
transfusion. There are challenges such as the need for blood components
products to meet the universal needs as it had become a public health
challenge. The current paper is discussing blood transfusion with reference to
literature to investigate issues such as need for industrial RBC, methods that
are used for producing RBC and the limitations to the process as well as the
challenges to it in the current and future. It also discusses Storage of RBC
effect membrane composition and large‐scale cost‐effective production of RBC.
Introduction
Blood transfusion in Oman dates back to the medical services
movement in the 1970s. Sultanate of Oman
is one of the young countries in the field of blood transfusion. Oman used to import blood units from other
advanced countries in that field. In early 1990, Ministry of Health has decided
to rely on indigenous blood donation as a safer alternative. This was achieved
by organizing blood donation drive twice or three times a month. In the mid of
1990 Oman was successfully self-sufficient to meet the national demands. However,
to face the enormous rise in Oman population we must find alternative to the
traditional blood transfusion. The production of industrial RBCs is an
excellent potential alternative. (Joshi et al, 2010)
Blood transfusion definition
Blood transfusion is defined as the process
of blood transferring into the individual's blood circulation. Transfusions are
used in many medical cases for replacement of blood lost components. It is an
important process that is included within the modern health care. When it is
used effectively, it can help in improving people's lives and health. Blood
transfusion carries many risks such as transmitting diseases that are made of
infectious agents, for example, HIV, syphilis, hepatitis viruses and others.
Close collaboration that occurs between clinicians and blood transfusion
service in managing the elements of the transfusion process can reduce the
risks that associate blood transfusion. Blood transfusion is taking blood or
blood components of a person to another who is in need for it. It is a
life-saving process for replacing blood products that are lost during bleeding
or depression of the patient's bone marrow. It is a safe method for saving
people in need for blood and it should be ensured by checking the blood is safe
and healthy and suitable for patient's blood type. Transfusion requires high
planning levels to be safe and should be done after investigating if the
patient is eligible for it or not. When blood transfusion is tested, reverse
effect can be stopped. Red blood
cell (RBC) production (erythropoiesis) occurs in the bone marrow
of the person under the hormone erythropoietin (EPO) control. In addition to
erythropoietin, red blood cell production needs adequate substrates
supplies including iron, folate, vitamin B12, and heme. RBCs has 120 days
surviving limit.
Need for industrial RBC
The need for blood transfusion arises
because of conditions rising from medical emergencies to genetic hemolytic
disorders such as sickle cell anemia, leukemia and other disorders. Some of
those patients are transfused throughout their lives and receive thousands of
blood units. As more as the patient is transfused throughout their lives, the
more risk of immunization against allogenic red blood cells increases which may
result in transfusion reactions and probability of fatal complications. As a
result, the availability of blood components products to meet the universal
needs had become a public health challenge. In the early 90s, scientists
worldwide were able to investigate the industrial production of red blood cells
and with deep understanding of the process, scientists were able to culture
blood cells in the lab. The industrial RBCs are easily produced from using
embryonic stem cells with the presence of a micro environment and this could be
cytokines, syrum and appropriate physical condition. Scientists found that
blood groups and other genetic mutations can be altered during the process.
Thus industrial RBCs can be successfully used for patients with rare blood
disorders. (Douay, 2018)
Methods used for producing RBC
There are methods for production of RBCs
such as the first method which is producing it in liquid culture and this
method was developed such as a procedure of two steps that was first designed
to amplifying and then favor the erythroid progenitors maturation to exist in
the umbilical cord as well as in the peripheral blood of the adult. This method
is effective in erythroid precursors production but at the same time it can't
afford great numbers of RBCs and conditioned medium and required serum. There
are other methods that can improve that protocol such as amplifying cord blood
stem and also progenitor cells that can apply the usage of certain defined
conditions. There are other methods that were developed by Beug group as they
developed SED which is a group of factors that include SCF stem cell factor
joined with dexamethasone and erythropoietin which are used for inducing extra
subset of progenitors extensive proliferation which makes difference within the
stress erythroblasts.
Limitation of the process
Those limitations include leukocytosis as WBC
in concentrations that go beyond the linearity limits related to the system
will need blood sample dilution. When diluted sample is re-assayed, this will
help in getting the right assay value. Another limitation is Nucleated Red
Blood Cells, NRBC which refers to red blood cells that are immature and
nucleated as they are different from mature RBCs and not large which makes them
lymphocyte results. RBC limitations include Leukocytosis with concurrent anemia.
In samples that have high WBC and low RBC, the WBC may lead to a false RBC
count increasing. Others are Agglutinated Red Blood Cells and Cold Agglutinins.
There are also the HGB limitations such as Unlysed Red Blood Cells, Leukocytosis
and Lipemia, hyperproteinemia and hyperbilirubinemia. Others include MCV/HTC
limitations such as Red Blood Cell Agglutination and Thrombocytosis (elevated
PLT). There are also PLT/MPV limitations such as Microcytosis (small RBC, low MCV) and Agglutinated
RBCs.
Present & future challenges
In countries that have high income and
development, challenges are mainly in transfusion that impasse as a result of secondary
hyperimmunization with polytransfusion as well as the population aging that has
two important consequences which are blood cancer development that increasing
with age and the reduction of number of people who donate blood and this
reduces the blood products matching requirements of blood transfusion.
Storage of RBC effect membrane
composition
The storage lesion is mainly a denomination
which has all different changes occurring as RBCs age during storage solution.
Haemolysis is the result of that change associated with increase in the haeme,
haemoglobin and extracellular free-iron which results in reduced bioactivity in
the nitric oxide due to morphological changes in addition to some lactic acid
accumulation and this can also lead to reduction in the glycolysis rate and the
2,3-DPG and ATP. Then haemolysis can be affected by these changes and lead to
different age classifications related to the RBC units. It was also regarded
that the transfusion safety can be affected by mtDNA and EVs. This can affect
the immune system of the recipient. Bioactive lipids Accumulation of in the
period of RBC storage was regarded as a supposed source of post-transfusion
sequelae occurring into vulnerable populations.
Large‐scale cost‐effective production of
RBC
The culture conditions can be improved for
reaching the required concentrations as there are many factors that can make
the RBC culture such a unique and effective one and they have to be well
investigated. Among those factors are blood shortage and technical methods,
culture time, cell source, units of blood and co-culture. They are great
advances that can help improve the process representing technology to future
large‐scale production. There should also be adaptation for each CB unit as
there will be difference in the optimal conditions for each of them. It will
also be good to watch cells differentiation in order to reach compromise
between the maturation and expansion.
Mitochondrial Superoxide Reduction &
Cytokine Secretion Skewing by Carbon Nanotube Scaffolds Enhance Ex Vivo
Expansion of Human Cord Blood Hematopoietic Progenitors
In 1989, umbilical cord blood (UCB) was
used for treatment of Fanconi’s anemia1 in a patient who understood his
potential as an alternative hematopoietic stem and progenitor (HSPC) cell
source2 to make transplantation of hematopoietic stem cell (HSC). There is higher proliferative capacity for
the UCB immature cells it also has longer
telomeres and less graft-versus-host-disease incidence. There are characterizations
for the immature cells lies in the UCB such as having higher proliferative
capacity, lower incidence of graft-versus-host-disease and longer telomeres as
this is when they are compared to the marrow of the bones.
It is supposed that there is at least about
25.000 HSPC in the one UCB milliliter and that amount is not enough for adult
effective transplantation needs. Scientisits in past times tried to do their
best to improve the UCB cell number with the help of cytokines, biomimetic
scaffolds, mesenchymal stromal cell co-cultures and even dual UCB
transplantation5. There is here a
carboxylic acid (-COOH) functionalized single-walled carbon nanotubes (f-SWCNT)
that work as a novel biomimetic scaffold that can be used as supporting for
HSPC vivo expansion. Such carbon cylindrical allotropes are applied already in
many biomedical research areas as well as drug delivery applications in
addition to cell tracking and tissue engineering too.
Complications that are serious
Large blood volume transfusion can carry
with it big complications that can be serious. Such common reactions may have
with them febrile non-hemolytic transfusion reactions (FNHTR), hemolytic
reactions, transfusion-related acute lung injury (TRALI), nosocomial infections
likely secondary to immunosuppression, reperfusion injury ,
transfusion-associated circulatory overload (TACO), and allergic transfusion
reactions (ATR). Such complications can affect the transfused blood and there
are some factors that may affect the injurious factors such as the stored
cytokines, the RBC storage lesion, donor antigens, RBC-derived microparticles
and donor leukocytes[13].
RBC-derived microparticles as this can be regarded in the models of provoke
lung injury in animal and activate lung endothelial cells.
Plasma transfusion complications
Platelet transfusion is usually presented
for either bleeding prophylaxis or for purposes of therapy. It can be seen for
Prophylactic transfusion which is existing in thrombocytopenic patients or in
patients having dysfunctional platelets.
It may bear the risk of bleeding as a consequence when accompany
neurosurgery or ocular surgery where it becomes high or when it becomes lower in cases of
insertion of a central line. There are usual infectious complications and there
are also subsequent platelet transfusion refractoriness that is subsequent for
platelet transfusion. In such cases the patient can take pro-coagulant products
that can include , amicar or tranexamic acid, prothrombin complex concentrates,
cryoprecipitate and recombinant factor seven. The best method for reduction of
morbidity that associates transfusion is reducing the blood product usage as
this can be applied by reducing phlebotomy that are not necessary and using
smaller collection tubes or by using limited suitable pharmacologic agents including
erythropoietin or using synthetic blood products substitutions or hemoglobin
based oxygen carriers.
Febrile transfusion reactions as Non-Infectious
Risks of Transfusion
Reactions of febrile transfusion are
referred to as a one-degree centigrade that is high in temperature in about
three hours of transfusion and they don't have explanations by hemolytic
reaction or sepsis. There is variation in the reported incidence that suggests
that febrile reactions can be reduced through red cell units leukoreduction.
There is a 1:330 red cell average rate and 1:20 relates to platelet
transfusions. There can be some features accompanying ferbrile transfusion
reactions such as rigors, chills or feeling of discomfort. It is suggested in
some research that pre-medication can't reduce febrile risk or reaction of allergic non-hemolytic
transfusion. Ferbile reactions can be treated with transfusion entails
discontinuation as well as supportive patient care and there can be also
antipyretic therapy.
Zika virus as a complication
Zika virus first outbreak happened in 2007
and the blood transfusion processes had a big role in spreading the virus since
2013. The virus is a mosquito born one and blood donors should be tested for
finding it in their blood before blood transfusion operations occur. It should
be classified as a major high risk agent that can passively affect the lives of
blood recipients. There are measures that can prevent Zika from affecting blood
transfusion processes such as having blood deferral that is temporary for blood
donors, self- report the virus symptoms by donors if they have it and blood
products pathogen inactivation and others. It is supposed that there is risk in
all blood donors which makes it important to apply Pathogen-inactivation methods
that can ensure suitable flavivirus reduction level that is found in platelets
and plasma but still the problem lies in red blood cells that include the most
of components of the transfused blood.
References
1. Brian M. Gilliss, MD, MS, Resident
Physician, Mark R. Looney, MD, Assistant Professor, and Michael A. Gropper, MD,
PhD, Professor and Vice-Chair. (2011). ' Reducing Non-Infectious Risks of Blood
Transfusion.' https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3162102/
2. Douay, L. (2018). ' Why industrial
production of red blood cells from stem cells is essential for tomorrow’s blood
transfusion.' https://www.futuremedicine.com/doi/full/10.2217/rme-2018-0025
3. Medonic.se, (2019). ' Parameter Limitations of Automated Blood
Cell Counters.' https://www.medonic.se/download/distributors/other/Parameter_Limitations.pdf
4. Rousseau, G. Giarratana, M. Douay, L. (2013). ' Large‐scale production of
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5. Stramer SL Hollinger FB Katz LM et al. Emerging
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6. TAKEOKA, S. (2005). ' Developmental Trend of Artificial Blood
(Artificial Red Blood Cells)'. http://www.med.or.jp/english/pdf/2005_03/135_139.pdf
7. Young Kim, Brent T Xia, Alex L Chang, and
Timothy A Pritts. (2016). ' Role of Leukoreduction of Packed Red Blood Cell
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