N 13. Blood. Blood groups. Leukemia
Blood is a
highly specialized circulating tissue
consisting of several types of cells suspended in a fluid medium known as plasma.
The cellular constituents are: red blood
cells, which carry respiratory gases and give it its red color
because they contain haemoglobin (an iron-containing protein that binds oxygen
in the lungs and transports it to tissues in the body), white blood
cells (leukocytes), which fight disease, and platelets,
cell fragments which play an important part in the clotting of the blood.
Medical terms related to blood
often begin with hemo- or hemato- (BE:
haemo- and haemato-) from the Greek
word "haima" for "blood." Anatomically, blood is
considered a connective tissue from both its origin in the
bones and its function.
Human blood smear:
a - erythrocytes;
b - neutrophil;
c - eosinophil;
d - lymphocyte.
Blood
is a constantly circulating fluid providing the body with nutrition, oxygen,
and waste removal. Blood is mostly liquid, with numerous cells and proteins
suspended in it, making blood "thicker" than pure water. The average
person has about 5 liters
(more than a gallon) of blood.
A
liquid called plasma makes up about half of the content of blood. Plasma
contains proteins that help blood to clot, transport substances through the
blood, and perform other functions. Blood plasma also contains glucose and
other dissolved nutrients.
About
half of blood volume is composed of blood cells:
• Red blood cells, which carry oxygen to the
tissues
• White blood cells, which fight infections
• Platelets, smaller cells that help blood to
clot
Blood
is conducted through blood vessels (arteries and veins). Blood is prevented
from clotting in the blood vessels by their smoothness, and the finely tuned
balance of clotting factors.
Blood
Conditions
Hemorrhage
(bleeding): Blood leaking out of blood vessels may be obvious, as from a wound
penetrating the skin. Internal bleeding (such as into the intestines, or after
a car accident) may not be immediately apparent.
Hematoma: A collection of blood inside the
body tissues. Internal bleeding often causes a hematoma.
Leukemia:
A form of blood cancer, in which white blood cells multiply abnormally and
circulate through the blood. The excessive large numbers of white cells deposit
in the body's tissues, causing damage.
Multiple myeloma: A form of blood cancer of
plasma cells similar to leukemia. Anemia, kidney failure and high blood calcium
levels are common in multiple myeloma.
Lymphoma: A form of blood cancer, in which
white blood cells multiply abnormally inside lymph nodes and other tissues. The
enlarging tissues, and disruption of blood's functions, can eventually cause
organ failure.
Anemia:
An abnormally low number of red blood cells in the blood. Fatigue and
breathlessness can result, although anemia often causes no noticeable symptoms.
Hemolytic
anemia: Anemia caused by rapid bursting of large numbers of red blood cells
(hemolysis). An immune system malfunction is one cause.
Hemochromatosis:
A disorder causing excessive levels of iron in the blood. The iron deposits in
the liver, pancreas and other organs, causing liver problems and diabetes.
Sickle cell disease: A genetic condition in
which red blood cells periodically lose their proper shape (appearing like
sickles, rather than discs). The deformed blood cells deposit in tissues,
causing pain and organ damage.
Bacteremia:
Bacterial infection of the blood. Blood infections are serious, and often
require hospitalization and continuous antibiotic infusion into the veins.
Malaria:
Infection of red blood cells by Plasmodium, a parasite transmitted by
mosquitos. Malaria causes episodic fevers, chills, and potentially organ
damage.
Thrombocytopenia:
Abnormally low numbers of platelets in the blood. Severe thrombocytopenia may
lead to bleeding.
Leukopenia:
Abnormally low numbers of white blood cells in the blood. Leukopenia can result
in difficulty fighting infections.
Disseminated intravascular coagulation (DIC):
An uncontrolled process of simultaneous bleeding and clotting in very small
blood vessels. DIC usually results from severe infections or cancer.
Hemophilia:
An inherited (genetic) deficiency of certain blood clotting proteins. Frequent
or uncontrolled bleeding can result from hemophilia.
Hypercoaguable
state: Numerous conditions can result in the blood being prone to clotting. A
heart attack, stroke, or blood clots in the legs or lungs can result.
Polycythemia:
Abnormally high numbers of red blood cells in the blood. Polycythemia can
result from low blood oxygen levels, or may occur as a cancer-like condition.
Deep
venous thrombosis (DVT): A blood clot in a deep vein, usually in the leg. DVTs
are dangerous because they may become dislodged and travel to the lungs,
causing a pulmonary embolism (PE).
Myocardial
infarction (MI): Commonly called a heart attack, a myocardial infarction occurs
when a sudden blood clot develops in one of the coronary arteries, which supply
blood to the heart.
Blood
Tests
Complete
blood count: An analysis of the concentration of red blood cells, white blood
cells, and platelets in the blood. Automated cell counters perform this test.
http://www.webmd.com/a-to-z-guides/complete-blood-count-cbc
Blood
smear: Drops of blood are smeared across a microscope slide, to be examined by
an expert in a lab. Leukemia, anemia, malaria, and numerous other blood
conditions can be identified with a blood smear.
Blood
type: A test for compatibility before receiving a blood transfusion. The major
blood types (A, B, AB, and O) are determined by the protein markers (antigens)
present on the surface of red blood cells.
Coombs
test: A blood test looking for antibodies that could bind to and destroy red
blood cells. Pregnant women and people with anemia may undergo Coombs testing.
Blood
culture: A blood test looking for infection present in the bloodstream. If
bacteria or other organisms are present, they may multiply in the tested blood,
allowing their identification.
Mixing
study: A blood test to identify the reason for blood being "too thin"
(abnormally resistant to clotting). The patient's blood is mixed in a tube with
normal blood, and the mixed blood's properties may provide a diagnosis.
Bone
marrow biopsy: A thick needle is inserted into a large bone (usually in the
hip), and bone marrow is drawn out for tests. Bone marrow biopsy can identify
blood conditions that simple blood tests cannot.
Blood
Treatments
Chemotherapy:
Medicines that kill cancer cells. Leukemias and lymphomas are usually treated
with chemotherapy.
Blood
transfusion: A blood donor's red blood cells are separated from their plasma
and packed into a small bag. Transfusing the concentrated red blood cells into
a recipient replaces blood loss.
Platelet
transfusion: A blood donor's platelets are separated from the rest of blood and
concentrated into a plastic bag. Platelet transfusion is generally only
performed when platelet counts fall to very low levels.
Fresh
frozen plasma: A blood donor's plasma (liquid blood) is separated from the
blood cells, and frozen for storage. Plasma transfusion can improve blood
clotting and prevent or stop bleeding that's due to clotting problems.
Cryoprecipitate: Specific proteins are
separated from blood and frozen in a small volume of liquid. Cryoprecipitate transfusion
can replace specific blood clotting proteins when their levels are low, such as
in people with hemophilia.
Anticoagulation:
Medicines to "thin" the blood and prevent clotting in people at high
risk from blood clots. Heparin, enoxaparin (Lovenox) and warfarin (Coumadin)
are the medicines most often used.
Antiplatelet
drugs: Aspirin and clopidogrel (Plavix) interfere with platelet function and
help prevent blood clots, including those that cause heart attacks and strokes.
Antibiotics: Medicines to kill bacteria and
parasites can treat blood infections caused by these organisms.
Erythropoietin:
A hormone produced by the kidney that stimulates red blood cell production. A
manufactured form of erythropoietin can be given to improve the symptoms of anemia.
Bloodletting:
In people with problems caused by too much blood (such as from hemochromatosis
or polycythemia), occasional controlled removal of blood may be necessary.
Functions
Problems with blood composition
or circulation can lead to downstream tissue dysfunction. The term ischaemia
refers to tissue which is inadequately perfused with blood.
The blood is circulated around
the lungs
and body by the pumping
action of the heart.
Additional return pressure may be generated by gravity and the actions of
skeletal muscles. In mammals, blood is in equilibrium with lymph, which is
continuously formed from blood (by capillary ultrafiltration) and returned to
the blood (via the thoracic duct). The lymphatic circulation may
be thought of as the "second circulation".
Anatomy
of mammalian blood
Blood is composed of several
kinds of cells (occasionally called corpuscles); these formed
elements of the blood constitute about 45% of whole blood by volume, mostly
red blood cells. The other 55% is blood plasma,
a fluid that is the blood's liquid medium, appearing yellow in color. The
proportion of blood occupied by red blood cells is referred to as the hematocrit.
A scanning electron microscope (SEM) image
of normal circulating human blood. One can see red blood
cells, several white blood
cells including knobby lymphocytes,
a monocyte,
a neutrophil,
and many small disc-shaped platelets.
The normal pH of human arterial blood
is approximately 7.40 (normal range is 7.35-7.45), a weak alkaline solution.
Blood that has a pH below 7.35 is acidic, while blood pH above 7.45 is alkaline.
Blood pH along with arterial carbon dioxide tension (PaCO2) and HCO3
readings are helpful in determining the acid-base balance of the body. The respiratory system and urinary
system normally control the acid-base balance of blood as part of homeostasis.
Blood is about 7% of the human body weight,[1]
so the average adult has a blood volume of about 5 litres, of which 2.7-3 litres is plasma. Human
blood density is around 1060 kg/m³.[2]
The combined surface area of all the red cells in the human body would be
roughly 2,000 times as great as the body's exterior surface.[citation needed]
The cells are:
Red blood
cells or erythrocytes (96%)
In
mammals, mature red blood cells lack a nucleus
and organelles.
They contain the blood's haemoglobin and distribute oxygen. The red
blood cells (together with endothelial vessel cells and some other cells)
are also marked by glycoproteins that define the different blood types.
White blood
cells or leukocytes (3.0%)
White
blood cells are part of the immune system; they destroy infectious agents, pathogens.
Platelets
or thrombocytes (1.0%)
Platelets
are responsible for blood clotting (coagulation).
They change fibrinogen into fibrin. This fibrin creates a mesh onto which red
blood cells collect and clot. This clot stops more blood from leaving the body
and also helps to prevent bacteria from entering the body.
Blood plasma
is essentially an aqueous
solution containing 92% water, 8% blood plasma proteins,
and trace amounts of other materials. Some components are:
Together, plasma and cells form a
non-Newtonian fluid whose flow properties are
uniquely adapted to the architecture of the blood vessels.
The term serum refers to
plasma from which the clotting proteins have been removed. Most of the protein
remaining is albumin and immunoglobulins.
Physiology of blood
Production
and degradation
Blood cells are produced in the bone marrow,
this process is termed hematopoiesis. The proteinaceous component (including
clotting proteins) is produced overwhelmingly in the liver, while hormones are
produced by the endocrine glands and the watery fraction is
regulated by the hypothalamus and maintained by the kidney and
indirectly by the gut.
Blood cells are degraded by the spleen and the Kupffer cells
in the liver. The liver also clears some proteins, lipids and amino acids.
The kidney actively secretes waste products into the urine. Erythrocytes
usually live up to 120 days before they are systematically replaced by new
erythrocytes created by the process of hematopoiesis.
Transport of oxygen
Blood oxygenation is measured in
several ways, but the most important measure is the hemoglobin (Hb) saturation
percentage. This is a non-linear (sigmoidal) function of the partial
pressure of oxygen. About 98.5% of the oxygen in a sample of
arterial blood in a healthy human breathing air at normal pressure is
chemically combined with the Hb. Only 1.5% is physically dissolved in the other
blood liquids and not connected to Hb. The hemoglobin molecule is the primary
transporter of oxygen in mammals and many other species (for exceptions, see
below).
With the exception of pulmonary
and umbilical arteries and their corresponding
veins, arteries
carry oxygenated blood away from the heart and deliver it to the
body via arterioles
and capillaries,
where the oxygen is consumed; afterwards, venules and veins carry deoxygenated
blood back to the heart.
Differences in infrared
absorption between oxygenated and deoxygenated blood form the basis for
realtime oxygen saturation measurement in hospitals and ambulances.
Under normal conditions in humans
at rest, haemoglobin in blood leaving the lungs is about 98-99% saturated with
oxygen. In a healthy adult at rest, deoxygenated blood returning to the lungs
is still approximately 75% saturated.[3][4]
Increased oxygen consumption during sustained exercise reduces the oxygen
saturation of venous blood, which can reach less than 15% in a trained athlete;
although breathing rate and blood flow increase to compensate, oxygen
saturation in arterial blood can drop to 95% or less under these conditions.[5]
Oxygen saturation this low is considered dangerous in an individual at rest
(for instance, during surgery under anesthesia): "As a general rule, any
condition which leads to a sustained mixed venous saturation of less than 50%
will be poorly tolerated and a mixed venous saturation of less than 30% should
be viewed as a medical emergency."[6]
A fetus, receiving oxygen via the
placenta, is exposed to much lower oxygen pressures (about 20% of the level
found in an adult's lungs) and so fetuses produce another form of hemoglobin
with a much higher affinity for oxygen (hemoglobin F) in order to extract as
much oxygen as possible from this sparse supply.[7]
Substances other than oxygen can
bind to the hemoglobin; in some cases this can cause irreversible damage to the
body. Carbon monoxide for example is extremely
dangerous when absorbed into the blood. When combined with the hemoglobin, it
irreversibly makes carboxyhemoglobin which reduces the volume of
oxygen that can be carried in the blood. This can very quickly cause
suffocation, as oxygen is vital to many organisms (including humans). This
damage can occur when smoking a cigarette (or similar item) or in event of a fire. Thus carbon
monoxide is considered far more dangerous than the actual fire itself because
it reduces the oxygen carrying content of the blood.
Insects
In insects, the
blood (more properly called hemolymph) is not involved in the transport of oxygen. (Openings
called tracheae
allow oxygen from the air to diffuse directly to the tissues). Insect blood
moves nutrients to the tissues and removes waste products in an open system.
Small invertebrates
In some small invertebrates
like insects,
oxygen is simply dissolved in the plasma. Larger animals use respiratory
proteins to increase the oxygen carrying capacity. Hemoglobin is the most
common respiratory protein found in nature. Hemocyanin
(blue) contains copper and is
found in crustaceans
and mollusks.
It is thought that tunicates (sea squirts) might use vanabins
(proteins
containing vanadium)
for respiratory pigment (bright green, blue, or orange).
In many invertebrates, these
oxygen-carrying proteins are freely soluble in the blood; in vertebrates they
are contained in specialized red blood
cells, allowing for a higher concentration of respiratory pigments
without increasing viscosity or damaging blood filtering organs like the kidneys.
Deep sea invertebrates
Giant tube
worms have extraordinary hemoglobins that allow them to live in
extraordinary environments. These hemoglobins also carry sulfides normally
fatal in other animals.
Transport
of carbon dioxide
When systemic arterial blood
flows through capillaries, carbon dioxide diffuses from the tissues into the
blood. Some carbon dioxide is dissolved in the blood. Some carbon dioxide
reacts with hemoglobin and other proteins to form carbamino
compounds. The remaining carbon dioxide is converted to bicarbonate
and hydrogen ions
through the action of RBC carbonic anhydrase. Most carbon dioxide is
transported through the blood in the form of bicarbonate ions.
Transport
of hydrogen ions
Some oxyhemoglobin loses oxygen
and becomes deoxyhemoglobin. Deoxyhemoglobin has a much greater affinity for H+
than does oxyhemoglobin so it binds most of the hydrogen ions.
Color
In humans and other
hemoglobin-using creatures, oxygenated blood is bright red. This is due to
oxygenated iron in the red blood cells. Deoxygenated blood is a darker shade of
red, which can be seen during blood donation and when venous blood samples are
taken. However, due to an optical effect caused by the way in which light
penetrates through the skin, veins typically appear blue in colour. This has
led to a common misconception that venous blood is blue before it is exposed to
air. Another reason for this misconception is that medical charts always show
venous blood as blue in order to distinguish it from arterial blood which is
depicted as red on the same chart.
The blood of horseshoe
crabs is blue, which is a result of its high content in copper-based
hemocyanin instead of the iron-based hemoglobin found, for example, in humans.
Provision of force
In mammals the restriction of
blood flow is commonly used as a temporary provision of force, as in an erection.
Health and disease
Ancient Medicine
Hippocratic
medicine considered blood one of the four humors
(together with phlegm,
yellow bile
and black bile).
As many diseases were thought to be due to an excess of blood, bloodletting
and leeching
were a common intervention until the 19th century
(it is still used for some rare blood disorders).
In classical Greek medicine,
blood was associated with air, springtime, and with a merry and gluttonous (sanguine)
personality. It was also believed to be produced exclusively by the liver.
Diagnosis
Blood
pressure and blood tests are amongst the most commonly
performed diagnostic investigations that directly concern the blood.
Pathology
Problems with blood circulation
and composition play a role in many diseases.
- Wounds can cause major blood loss (see bleeding).
The thrombocytes
cause the blood to coagulate, blocking relatively minor
wounds, but larger ones must be repaired at speed to prevent exsanguination.
Damage to the internal organs can cause severe internal bleeding, or hemorrhage.
- Circulation blockage can also create many medical
conditions from ischemia in the short term to tissue necrosis
and gangrene
in the long term.
- Hemophilia is a genetic illness that
causes dysfunction in one of the blood's clotting
mechanisms. This can allow otherwise inconsequential wounds to
be life-threatening, but more commonly results in hemarthrosis,
or bleeding into joint spaces, which can be crippling.
- Leukemia is a group of cancers of the blood-forming tissues.
- Major blood loss, whether traumatic or not (e.g.
during surgery), as well as certain blood diseases like anemia
and thalassemia,
can require blood transfusion. Several countries
have blood
banks to fill the demand for transfusable blood. A person
receiving a blood transfusion must have a blood
type compatible with that of the donor.
- Blood is an important vector of infection. HIV, the virus
which causes AIDS,
is transmitted through contact between blood, semen,
or the bodily secretions of an infected person. Hepatitis
B and C are transmitted primarily through blood
contact. Owing to blood-borne infections, bloodstained
objects are treated as a biohazard.
- Bacterial infection of the blood is bacteremia
or sepsis.
Viral Infection is viremia. Malaria and trypanosomiasis
are blood-borne parasitic infections.
Treatment
Blood
transfusion is the most direct therapeutic use of blood. It is
obtained from human donors by blood
donation. As there are different blood types,
and transfusion of the incorrect blood may cause severe complications, crossmatching
is done to ascertain the correct type is transfused.
Other blood products administered
intravenously
are platelets, blood plasma, cryoprecipitate and specific coagulation factor
concentrates.
Many forms of medication (from antibiotics
to chemotherapy)
are administered intravenously, as they are not readily or adequately absorbed
by the digestive tract.
As stated above, some diseases
are still treated by removing blood from the circulation.
It is the fluid part of the blood
that saves lives where severe blood loss occurs, other preparations can be
given such as ringers atopical plasma volume expander as a non-blood
alternative, and these alternatives where used are rivalling blood use when
used.
Blood type
Blood
type (or blood group) is determined, in part, by the ABO
blood group antigens present on red blood cells.
A blood
type (also called a blood group) is a classification of blood based on the
presence or absence of inherited antigenic
substances on the surface of red blood
cells (RBCs). These antigens may be proteins,
carbohydrates,
glycoproteins
or glycolipids,
depending on the blood group system, and some of these antigens are also
present on the surface of other types of cells of various tissues. Several of these red blood cell
surface antigens, that stem from one allele (or very
closely linked genes),
collectively form a blood group system.
The ABO blood group system and the Rhesus blood group system are more likely
to cause harmful immunological reactions than the other blood
group systems. In the routine blood
transfusion work of a blood bank,
the presence or absence of the three most significant blood group antigens, the
A antigen, the B antigen and the RhD antigen (also known as the Rhesus factor
or Rhesus D antigen), is determined. This gives the ABO blood group and the RhD antigen
status, which are reflected in the common terminology A positive, O
negative, etc. with the capital letters (A, B or O) referring to the ABO
blood group, and positive or negative referring to the presence or absence of
the RhD antigen of the Rhesus blood group system. In the routine preparation
and selection of donor blood for blood transfusion, it is not
necessary to determine the status of any more blood groups (or antigens),
because antibody screening and cross-matching
prior to transfusion, detects if there are any other blood group
incompatibilities between potential donor blood and intended recipients.
If an
individual is exposed to a blood group antigen that is not recognised as self,
the immune system
will produce antibodies
that can specifically bind to that particular blood group antigen and an
immunological memory against that antigen is formed. The individual will have
become sensitized to that blood group antigen. These antibodies can bind to
antigens on the surface of transfused red blood
cells (or other tissue cells) often leading to destruction of the
cells by recruitment of other components of the immune system. It is vital that
compatible blood is selected for transfusion
and that compatible tissue is selected for organ
transplantation. Transfusion reactions involving minor
antigens or weak antibodies may lead to minor problems. However, more serious
incompatibilities can lead to a more vigorous immune response
with massive RBC
destruction, low blood pressure, and even death.
Blood
types are inherited
and represent contributions from both parents. Often, pregnant
women carry a fetus
with a different blood type from their own, and sometimes the mother forms
antibodies against the red blood cells of the fetus, which causes hemolysis
of fetal RBCs, and which in turn can lead to low fetal blood counts,
a condition known as hemolytic disease of the newborn.
Some blood types are associated with inheritance of other diseases; for
example, the Kell antigen is associated with McLeod
syndrome.[1]
Certain blood types may affect susceptibility to infections, an example being
the resistance to specific malaria species seen in individuals lacking the Duffy antigen.[2]The
Duffy antigen, as a result of natural
selection, is more common in ethnic groups from areas with a high
incidence of malaria.[3]
The two
most significant blood group systems were discovered during early experiments
with blood transfusion: the ABO group in 1901[4]
and the Rhesus group in 1937.[5]
Development of the Coombs test in 1945,[6]
the advent of transfusion medicine, and the
understanding of hemolytic disease of the newborn
led to discovery of more blood groups. Today, a total of 29 human blood group systems are recognized
by the International Society of Blood
Transfusion (ISBT).[7] A complete blood type would describe a full
set of 29 substances on the surface of RBCs, and an individual's blood type is
one of the many possible combinations of blood group antigens. Across the 29
blood groups, over 600 different blood group antigens have been found,[8]
but many of these are very rare or are mainly found in certain ethnic groups.
Almost always, an individual has the same blood group for life; but very
rarely, an individual's blood type changes through addition or suppression of
an antigen in infection,
malignancy
or autoimmune disease.[9] Blood types have been used in forensic
science and in paternity
testing, but this use is being replaced by DNA analysis,
which provides greater certitude.
Blood group systems
ABO
blood group system - diagram showing the carbohydrate chains which
determine the ABO blood group
ABO
blood group system
The ABO
system is the most important blood group system in human blood transfusion.
The associated anti-A antibodies and anti-B antibodies are usually IgM antibodies. ABO IgM
antibodies are produced in the first years of life by sensitization to
environmental substances such as food, bacteria
and viruses.
The "O" in ABO is often called "0" (zero/null) in other
languages.[10]
Rhesus
blood group system
The Rhesus
system is the second most significant blood group system in human blood
transfusion. The most significant Rhesus antigen is the RhD antigen because
it is the most immunogenic of the five main rhesus antigens. It is common for
RhD negative individuals not to have any anti-RhD IgG or IgM antibodies,
because anti-RhD antibodies are not usually produced by sensitization against
environmental substances. However, RhD negative individuals can produce IgG anti-RhD antibodies
following a sensitizing event: possibly a fetomaternal transfusion of blood
from a fetus in pregnany or occasionally a blood transfusion with RhD positive RBCs.
Table of ABO and Rh distribution by nation
Overall,
type O blood is the most common blood type in the world.[21] Type A blood is more prevalent in Central
and Eastern Europe countries.[21] Type B blood is most prevalent in
Chinese/Asian communities when compared to other races.[21] Type AB blood is easier to find in Japan, China
and Pakistan[21].
The
associated anti-A and anti-B antibodies are usually IgM antibodies, which are
usually produced in the first years of life by sensitization to environmental
substances such as food, bacteria, and viruses. ABO blood types are also
present in some other animals, for example apes such as chimpanzees, bonobos,
and gorillas.
History
of discoveries
The
ABO blood group system is widely credited to have been discovered by the
Austrian scientist Karl Landsteiner, who found three different blood types in
1900; he was awarded the Nobel Prize in Physiology or Medicine in 1930 for his
work. Due to inadequate communication at the time it was subsequently found
that Czech serologist Jan Janský had independently pioneered the
classification of human blood into four groups, but Landsteiner's independent
discovery had been accepted by the scientific world while Janský
remained in relative obscurity. Janský's classification is however still
used in Russia and states of
former USSR
(see below). In America,
Moss[who?] published his own (very similar) work in 1910.
Landsteiner
described A, B, and O; Alfred von Decastello and Adriano Sturli discovered the fourth
type, AB, in 1902. Ludwik Hirszfeld and E. von Dungern discovered the
heritability of ABO blood groups in 1910–11, with Felix Bernstein demonstrating
the correct blood group inheritance pattern of multiple alleles at one locus in
1924. Watkins and Morgan, in England,
discovered that the ABO epitopes were conferred by sugars, to be specific,
N-acetylgalactosamine for the A-type and galactose for the B-type. After much
published literature claiming that the ABH substances were all attached to
glycosphingolipids, Laine's group (1988) found that the band 3 protein
expressed a long polylactosamine chain that contains the major portion of the
ABH substances attached. Later, Yamamoto's group showed the precise glycosyl
transferase set that confers the A, B and O epitopes.
ABO
antigens
Diagram
showing the carbohydrate chains that determine the ABO blood group
The
H antigen is an essential precursor to the ABO blood group antigens. The H
locus, which is located on chromosome 19, contains 3 exons that span more than
5 kb of genomic DNA; it encodes a fucosyltransferase that produces the H
antigen on RBCs. The H antigen is a carbohydrate sequence with carbohydrates
linked mainly to protein (with a minor fraction attached to ceramide moiety).
It consists of a chain of β-D-galactose, β-D-N-acetylglucosamine,
β-D-galactose, and 2-linked, α-L-fucose, the chain being attached to
the protein or ceramide.
The
ABO locus, which is located on chromosome 9, contains 7 exons that span more
than 18 kb of genomic DNA. Exon 7 is the largest and contains most of the
coding sequence. The ABO locus has three main alleleic forms: A, B, and O. The
A allele encodes a glycosyltransferase that bonds α-N-acetylgalactosamine
to the D-galactose end of the H antigen, producing the A antigen. The B allele
encodes a glycosyltransferase that bonds α-D-galactose to the D-galactose
end of the H antigen, creating the B antigen.
In
the case of the O allele, when compared to the A allele, exon 6 lacks one
nucleotide (guanine), which results in a loss of enzymatic activity. This
difference, which occurs at position 261, causes a frameshift that results in
the premature termination of the translation and, thus, degradation of the
mRNA. This results in the H antigen remaining unchanged in case of O groups.
The
majority of the ABO antigens are expressed on the ends of long polylactosamine
chains attached mainly to band 3 protein, the anion exchange protein of the RBC
membrane, and a minority of the epitopes are expressed on neutral
glycosphingolipid.
Serology
Anti-A
and anti-B antibodies (called isohaemagglutinins), which are not present in the
newborn, appear in the first years of life. They are isoantibodies, that is,
they are produced by an individual against antigens produced by members of the
same species (isoantigens). Anti-A and anti-B antibodies are usually IgM type,
which are not able to pass through the placenta to the fetal blood circulation.
O-type individuals can produce IgG-type ABO antibodies.
Origin
theories
It
is possible that food and environmental antigens (bacterial, viral, or plant
antigens) have epitopes similar enough to A and B glycoprotein antigens. The
antibodies created against these environmental antigens in the first years of
life can cross-react with ABO-incompatible red blood cells (RBCs) that it comes
in contact with during blood transfusion later in life. Anti-A antibodies are
hypothesized to originate from immune response towards influenza virus, whose
epitopes are similar enough to the α-D-N-galactosamine on the A glycoprotein
to be able to elicit a cross-reaction. Anti-B antibodies are hypothesized to
originate from antibodies produced against Gram-negative bacteria, such as E.
coli, cross-reacting with the α-D-galactose on the B glycoprotein.
The
"Light in the Dark theory" (DelNagro, 1998) suggests that, when
budding viruses acquire host cell membranes from one human patient (in
particular, from the lung and mucosal epithelium where they are highly
expressed), they also take along ABO blood antigens from those membranes, and
may carry them into secondary recipients where these antigens can elicit a host
immune response against these non-self foreign blood antigens. These
viral-carried human blood antigens may be responsible for priming newborns into
producing neutralizing antibodies against foreign blood antigens. Support for
this theory has come to light in recent experiments with HIV. HIV can be
neutralized in in vitro experiments using antibodies against blood group
antigens specifically expressed on the HIV-producing cell lines.
The
"Light in the Dark theory" suggests a novel evolutionary hypothesis:
there is true communal immunity, which has developed to reduce the
inter-transmissibility of viruses within a population. It suggests that
individuals in a population supply and make a diversity of unique antigenic
moieties so as to keep the population as a whole more resistant to infection. A
system set up ideally to work with variable recessive alleles.
However,
it is more likely that the force driving evolution of allele diversity is
simply negative frequency-dependent selection; cells with rare variants of
membrane antigens are more easily distinguished by the immune system from
pathogens carrying antigens from other hosts. Thus, individuals possessing rare
types are better equipped to detect pathogens. The high within-population
diversity observed in human populations would, then, be a consequence of
natural selection on individuals.
Nonantigen
biology
The
carbohydrate molecules on the surfaces of red blood cells have roles in cell
membrane integrity, cell adhesion, membrane transportation of molecules, and
acting as receptors for extracellular ligands, and enzymes. ABO antigens are
found having similar roles on epithelial cells as well as red blood cells.
Transfusion
reactions
Due
to the presence of isoantibodies against non-self blood group antigens,
individuals of type A blood group immediately raise anti-B antibodies against
B-blood group RBCs if transfused with blood from B group. The anti-B antibodies
bind to B antigens on RBCs and cause complement-mediated lysis of the RBCs. The
same happens for B and O groups (which raises both anti-A and anti-B
antibodies). However, only blood group AB does not have anti-A and anti-B
isoantibodies. This is because both A and B-antigens are present on the RBCs
and are both self-antigens, hence they can receive blood from all groups and
are universal recipients.
As
far as transfusion compatibility is concerned, it is not strictly as simple as
matching A, B, and O groups. In other words, no individual will ever receive a
blood transfusion based on the ABO system alone. The rhesus factor must also be
considered. Together, the rhesus factor and ABO grouping are the two most important
compatibility factors to consider. An individual may be Rh+ or Rh-. In simpler
terms, if an individual is blood type A and positive for the rhesus factor,
then he or she is deemed "A+".
ABO
and Rh blood type donation showing matches between donor and recipient types Donors
O+ A+ B+ AB+ O-
** A- B- AB-
Recipients O+ ✔ ✔
A+ ✔ ✔ ✔ ✔
B+ ✔ ✔ ✔ ✔
AB+ * ✔ ✔ ✔ ✔ ✔ ✔ ✔ ✔
O- ✔
A- ✔ ✔
B- ✔ ✔
AB- ✔ ✔ ✔ ✔
* Type
AB+ is the universal recipient: Although those with AB blood type may be
referred to as universal recipients, in actuality, type AB+ blood is that of
the universal recipient, whereas type AB- is not. This is an important
distinction to make.
**
Because A-, A+, B-, B+, AB-, AB+, O- and O+ individuals can all receive blood
from donors of type O- blood, an individual with type O- blood is deemed a
universal donor. In a similar manner, O+ is not the universal donor blood type.
One
caveat to this axiom of 'universal donor' is that this applies to packed RBCs,
and not to whole blood products. Using the first table, type O carries anti-A
and anti-B antibodies in the serum. To transfuse a type A, B, or AB recipient
with type O whole blood would produce a hemolytic transfusion reaction due to
the antibodies found in the serum of whole blood.
No
antibodies are formed against the H antigen, except in those individuals with
the Bombay
phenotype.
In
ABH secretors, roughly 80% of the human population, ABH antigens are secreted
by most mucus-producing cells of the body interfacing with the environment,
including lung, skin, liver, pancreas, stomach, intestines, ovaries, and
prostate.
ABO
hemolytic disease of the newborn
Main
article: Hemolytic disease of the newborn (ABO)
ABO
blood group incompatibilities between the mother and child does not usually
cause hemolytic disease of the newborn (HDN) because antibodies to the ABO
blood groups are usually of the IgM type, which do not cross the placenta;
however, in an O-type mother, IgG ABO antibodies are produced and the baby can
develop ABO hemolytic disease of the newborn.
Inheritance
A
and B are codominant, giving the AB phenotype.
Blood
groups are inherited from both parents. The ABO blood type is controlled by a
single gene (the ABO gene) with three alleles: i, IA, and IB. The gene encodes
a glycosyltransferase—that is, an enzyme that modifies the carbohydrate content
of the red blood cell antigens. The gene is located on the long arm of the
ninth chromosome (9q34).
The
IA allele gives type A, IB gives type B, and i gives type O. As both IA and IB
are dominant over i, only ii people have type O blood. Individuals with IAIA or
IAi have type A blood, and individuals with IBIB or IBi have type B. IAIB
people have both phenotypes, because A and B express a special dominance
relationship: codominance, which means that type A and B parents can have an AB
child. A type A and a type B couple can also have a type O child if they are
both heterozygous (IBi,IAi) The cis-AB phenotype has a single enzyme that
creates both A and B antigens. The resulting red blood cells do not usually
express A or B antigen at the same level that would be expected on common group
A1 or B red blood cells, which can help solve the problem of an apparently
genetically impossible blood group.
Distribution
and evolutionary history
The
distribution of the blood groups A, B, O and AB varies across the world
according to the population. There are also variations in blood type
distribution within human subpopulations.
In
the UK,
the distribution of blood type frequencies through the population still shows
some correlation to the distribution of placenames and to the successive
invasions and migrations including Vikings, Danes, Saxons, Celts, and Normans
who contributed the morphemes to the placenames and the genes to the
population.
Genetics
There
are two common O alleles, O01 and O02. These are identical to the group A
allele (A01) for the first 261 nucleotides, at which point a guanosine base is
deleted, resulting in a frame-shift mutation that produces a premature stop
codon and failure to produce a functional A or B transferase. This deletion is
found in all populations worldwide and presumably arose before humans migrated
out of Africa (50,000 to 100,000 years ago).
The second most common allele for group O (termed O02) is considered to be an
even more ancient than the O01 allele.
Some
evolutionary biologists theorize that the IA allele evolved earliest, followed
by O (by the deletion of a single nucleotide, shifting the reading frame) and
then IB. This chronology accounts for the percentage of people worldwide with
each blood type. It is consistent with the accepted patterns of early population
movements and varying prevalent blood types in different parts of the world:
for instance, B is very common in populations of Asian descent, but rare in
ones of Western European descent. Another theory states that there are four
main lineages of the ABO gene and that mutations creating type O have occurred
at least three times in humans. From oldest to youngest, these lineages
comprise the following alleles: A101/A201/O09, B101, O02 and O01. The continued
presence of the O alleles is hypothesized to be the result of balancing
selection. Both theories contradict the previously held theory that type O
blood evolved earliest.
Other
blood group systems
The International Society of Blood
Transfusion currently recognizes 29 blood group systems (including
the ABO and Rh systems).[7] Thus, in addition to the ABO antigens and
Rhesus antigens, many other antigens are expressed on the RBC surface membrane.
For example, an individual can be AB RhD positive, and at the same time M and N
positive (MNS system), K positive (Kell system
), Lea or Leb negative (Lewis system), and so on,
being positive or negative for each blood group system antigen. Many of the
blood group systems were named after the patients in whom the corresponding
antibodies were initially encountered.
Transfusion medicine is a specialized branch of hematology
that is concerned with the study of blood groups, along with the work of a blood
bank to provide a transfusion
service for blood and other blood products. Across the world, blood products
must be prescribed by a medical doctor (licensed physician
or surgeon)
in a similar way as medicines. In the USA, blood products are tightly regulated
by the Food
and Drug Administration.
Much of the routine work of a blood
bank involves testing blood from both donors and recipients to ensure
that every individual recipient is given blood that is compatible and is as
safe as possible. If a unit of incompatible blood is transfused
between a donor
and recipient, a severe acute immunological reaction, hemolysis
(RBC destruction), renal
failure and shock
are likely to occur, and death is a possibility. Antibodies can be highly
active and can attack RBCs and bind components of the complement
system to cause massive hemolysis of the transfused blood.
Patients
should ideally receive their own blood or type-specific blood products to
minimize the chance of a transfusion
reaction. Risks can be further reduced by cross-matching
blood, but this may be skipped when blood is required for an emergency. Cross-matching
involves mixing a sample of the recipient's blood with a sample of the donor's
blood and checking to see if the mixture agglutinates, or forms clumps.
If agglutination is not obvious by direct vision, blood bank technicians
usually check for agglutination
with a microscope.
If agglutination occurs, that particular donor's blood cannot be transfused to
that particular recipient. In a blood bank it is vital that all blood specimens
are correctly identified, so labeling has been standardized using a barcode
system known as ISBT
128.
Some
front-line military personnel choose to be tattooed
with their blood type in case they should need an emergency blood transfusion.
This was the case with frontline German Waffen-SS
during the World
War II; ironically this was an easy form of SS
identification.[22]
Rare blood
types can cause supply problems for blood
banks and hospitals. For example Duffy-negative
blood occurs much more frequently in people of African origin,[23]
and the rarity of this blood type in the rest of the population can result in a
shortage of Duffy-negative blood for patients of African ethnicity. Similarly
for RhD negative people, there is a risk associated with travelling to parts of
the world where supplies of RhD negative blood are rare, particularly East
Asia, where blood services may endeavor to encourage Westerners to
donate blood.[24]
In order to
provide maximum benefit from each blood donation and to extend shelf-life, blood
banks fractionate
some whole blood into several products. The most common of these products are
packed RBCs, plasma,
platelets,
cryoprecipitate,
and fresh
frozen plasma (FFP). FFP is quick-frozen to retain the labile clotting
factors V
and VIII,
which are usually administered to patients who have a potentially fatal
clotting problem caused by a condition such as advanced liver
disease, overdose of anticoagulant,
or disseminated
intravascular coagulation (DIC).
Units of packed red cells are made by
removing as as much of the plasma as possible from whole blood units.
Clotting
factors synthesized by modern recombinant
methods are now in routine clinical use for hemophilia,
as the risks of infection transmission that occur with pooled blood products
are avoided.
·
Blood group
AB individuals have both A and B antigens on the surface of
their RBCs, and their blood
serum does not contain any antibodies against either A or B antigen.
Therefore, an individual with type AB blood can receive blood from any group
(with AB being preferable), but can donate blood only to another group AB
individual.
·
Blood group A individuals have the A antigen on the surface of their RBCs, and blood
serum containing IgM
antibodies against the B antigen. Therefore, a group A individual can receive
blood only from individuals of groups A or O (with A being preferable), and can
donate blood to individuals of groups A or AB.
·
Blood group B individuals have the B antigen on their surface of their RBCs, and blood
serum containing IgM
antibodies against the A antigen. Therefore, a group B individual can receive
blood only from individuals of groups B or O (with B being preferable), and can
donate blood to individuals of groups B or AB.
·
Blood group O (or blood group zero in some countries) individuals do not have either A
or B antigens on the surface of their RBCs, but their blood
serum contains IgM
anti-A antibodies and anti-B antibodies against the A and B blood group
antigens. Therefore, a group O individual can receive blood only from a group O
individual, but can donate blood to individuals of any ABO blood group (ie A,
B, O or AB). If a blood transfusion is needed in a dire emergency, and the time
taken to process the recipient's blood would cause a detrimental delay, O Neg
blood is issued.
RBC
Compatibility chart
Type O donors can give to A, B & AB; donors of types A & B can give to AB.
A RhD negative patient (who has not been sensitized to RhD positive RBCs
and who does not have any anti-D antibodies) can receive RhD positive blood
cells, but this would cause sensitization to the RhD antigen, and a female
patient would become at risk for HDN.
Therefore, RhD positive blood is never given to RhD negative women of
childbearing age, and is only given to other RhD negative patients in extreme
circumstances, such as for a major bleed when stocks of RhD negative blood
units are very low at the blood bank. If a RhD negative patient has developed
anti-D antibodies, a subsequent exposure to RhD positive blood would lead to a
potentially dangerous transfusion reaction. Occasionally, for transfusion of
females above child-bearing age or of males, RhD positive blood is given to RhD
negative individuals (who do not have atypical red cell antibodies) when it is
necessary to conserve RhD negative blood stock in the blood bank in case RhD
negative blood is needed for people where sensitisation to RhD antigens could
cause serious medical problems.
The converse is not true; RhD
positive patients do not react to RhD negative blood.
Plasma compatibility chart
Plasma from type AB can be given to A, B & O; plasma from types A & B
can be given to O.
Donor-recipient
compatibility for blood
plasma is the reverse of that of RBCs. Plasma extracted from type AB
blood can be transfused to individuals of any blood group, but type O plasma
can be used only by type O recipients.
Rhesus D
antibodies are uncommon, so generally neither RhD negative nor RhD positive
blood contain anti-RhD antibodies. If a potential donor is found to have
anti-RhD antibodies or any strong atypical blood group antibody by antibody
screening in the blood bank, they would not be accepted as a donor; therefore,
all donor blood plasma issued by a blood bank can be expected to be free of RhD
antibodies and free of other atypical antibodies. Donor plasma issued from a
blood bank would be suitable for a recipient who may be RhD positive or RhD
negative, as long as blood plasma and the recipient are ABO compatible.
With regard
to transfusions of whole blood or packed red blood cells, individuals with
blood type O negative blood are often called universal donors, and those
with type AB positive blood are called universal recipients. Although,
blood donors with particularly strong anti-A, anti-B or any atypical blood
group antibody are excluded from blood donation, the terms universal donor
and universal recipient are an over-simplification, because they only
consider possible reactions of the recipient's anti-A and anti-B antibodies to
transfused red blood cells, and also possible sensitisation to RhD antigens.
The possible reactions of anti-A and anti-B antibodies present in the
transfused blood to the recipients RBCs are not considered, because a
relitively small volume of plasma containing antibodies is transfused.
By way of
example; considering the transfusion of O RhD negative blood (universal donor
blood) into a recipient of blood group A RhD positive, an immune reaction
between the recipient's anti-B antibodies and the transfused RBCs is not
anticipated, but the relatively small amount of plasma in the transfused blood
contains anti-A antibodies, which could react with the A antigens on the
surface of the recipients red blood cells, but a significant reaction is
unlikely because of the dilution factors. Rhesus D sensitisization is not
anticipated.
Additionally,
red blood cell surface antigens other than A, B and Rh D, might cause adverse
reactions and sensitization, if they can bind to the corresponding antibodies
to generate an immune response. Transfusions are further complicated because platelets
and white
blood cells (WBCs) have their own systems of surface antigens, and
sensitization to platelet or WBC antigens can occur as a result of transfusion.
With regard
to transfusions of plasma,
this situation is reversed. Type O plasma can be given only to O recipients,
while AB plasma (which does not contain anti-A or anti-B antibodies) can be
given to patients of any ABO blood group.
Importance of
Type O
Different
ethnic and racial groups also have different frequency of the main blood types
in their populations. For example, approximately 45 percent of Caucasians are
Type O, but 51 percent of African Americans and 57 percent of Hispanics are
Type O. Type O is routinely in short supply and in high demand by hospitals –
both because it is the most common blood type and because Type O-negative
blood, in particular, is the universal type needed for emergency transfusions.
Minority and diverse populations, therefore, play a critical role in meeting
the constant need for blood.
Rare Blood
Types
Red blood
cells carry markers called antigens on their surface that determine one’s blood
type. There are more than 600 known antigens besides A and B. Certain blood
types are unique to specific racial and ethnic groups. Therefore it is
essential that the donor diversity match the patient diversity. For example,
U-negative and Duffy-negative blood types are unique to the African American
community. So Sickle cell patients with these blood types must rely on donors
with matching blood types in the African American community.
When blood is
phenotypically matched (i.e., close blood type match), patients are at a lower
risk of developing complications from transfusion therapy. For this reason, it
is extremely important to increase the number of available blood donors from
all ethnic groups.
Some Rare
Blood Types by Ethnic Group
Ethnic Group Rare Blood
Type
African-American U-, Fy(a-b-)
Native American,
Alaskan Native RzRz
Pacific
Island, Asian Jk (a-b-)
Hispanic
Di(b-)
East
European/Russian Jews Dr(a-)
Caucasian
Kp(b-), Vel-
Blood
Components
In modern
medical treatments, patients may receive a pint of whole blood or just specific
components of the blood needed to treat their particular condition. Up to four
components can be derived from donated blood. This approach to treatment, referred
to as blood component therapy, allows several patients to benefit from one pint
of donated whole blood. The main transfusable blood components include:
Whole Blood
Whole blood
contains red cells, white cells, and platelets (~45% of volume) suspended in
plasma (~55% of volume).
Red cells
Red cells, or
erythrocytes, carry oxygen from the lungs to your body’s tissue and take carbon
dioxide back to your lungs to be exhaled.
Red Blood
Cells (RBCs) are perhaps the most recognizable component of whole blood. RBCs
contain hemoglobin, a complex protein containing iron that carries oxygen
through the body. The percentage of blood volume composed of red blood cells is
called the “hematocrit.” There are about one billion red blood cells in two to
three drops of blood, and for every 600 red blood cells, there are about 40
platelets and one white cell.
Manufactured
in the bone marrow, RBCs are continuously produced and broken down. They live
for about 120 days in the circulatory system.
Red blood
cells are prepared from whole blood by removing plasma, or the liquid portion
of the blood, and they are used to treat anemia while minimizing an increase in
blood volume. Improvements in cell preservation solutions over decades have
increased the shelf-life of red blood cells from 21 to 42 days.
RBCs may be
treated and frozen for an extended storage, of 10 years or more. Patients who
benefit most from transfusion of red blood cells include those with chronic
anemia resulting from kidney failure or gastrointestinal bleeding, and those
with acute blood loss resulting from trauma.
Prestorage
leukocyte-reduced red blood cells require special preparation by removing
leukocytes (white blood cells) by filtration shortly after donation. This is
done before storage because high numbers of leukocytes remaining in a unit of
RBCs during the storage process can fragment, deteriorate, and release
cytokines (chemicals that affect the inflammatory response). Leukocytes have
been implicated as a cause of reactions to a current and subsequent blood
transfusions in some transfusion recipients.
Platelets
Platelets, or
thrombocytes, are small, colorless cell fragments in the blood whose main
function is to interact with clotting proteins to stop or prevent bleeding.
Platelets are
small blood components that help the clotting process by sticking to the lining
of blood vessels. Platelets are made in the bone marrow and survive in the
circulatory system
Platelets are
prepared by using a centrifuge to separate the platelet-rich plasma from the
donated unit of whole blood.
Platelets may
also be obtained from a donor by a process known as apheresis, or
plateletpheresis. In this process, blood is drawn from the donor into an
apheresis instrument which separates the blood into its components, retains
some of the platelets, and returns the remainder of the blood to the donor.
This single
donor platelet product contains about six times as many platelets as a unit of
platelets obtained from whole blood. Platelets are used to treat a condition
called thrombocytopenia, in which there is a shortage of platelets, and they
are also used to treat platelet function abnormalities. Platelets are stored at
room temperature with constant agitation for 5 days.
Plasma
Plasma is a
fluid, composed of about 92% water, 7% vital proteins such as albumin, gamma
globulin, anti-hemophilic factor, and other clotting factors, and 1% mineral
salts, sugars, fats, hormones and vitamins.
Plasma is the
liquid portion of blood – a protein-salt solution in which red and white blood
cells and platelets are suspended. Plasma, which is 92 percent water,
constitutes 55 percent of blood volume. Plasma contains albumin (the chief
protein constituent), fibrinogen (responsible, in part, for the clotting of
blood) and globulins (including antibodies). Plasma serves a variety of
functions, from maintaining a satisfactory blood pressure and volume to
supplying
critical proteins for blood clotting and immunity. It also serves as the medium
for
exchange of
vital minerals such as sodium and potassium and helps to maintain a proper pH
(acid-base) balance in the body, which is critical to cell function. Plasma is
obtained by separating the liquid portion of blood from the cells.
Plasma is
frozen quickly after donation (up to 24 hours) to preserve clotting factors,
stored up to one year, and thawed shortly before use. It is commonly transfused
to trauma patients and patients with severe liver disease or multiple clotting
factor deficiencies.
Plasma
derivatives are concentrates of specific plasma proteins prepared from pools
(many donor units) of plasma. Plasma derivatives are obtained through a process
known as fractionation. The derivatives are treated with heat and/or solvent
detergent to kill certain viruses like those that cause HIV, hepatitis B, and
hepatitis C.
Plasma derivatives
include:
·
Factor VIII
Concentrate
·
Factor IX
Concentrate
·
Anti-Inhibitor
Coagulation Complex (AICC)
·
Albumin
·
Immune
Globulins, including Rh Immune Globulin
·
Anti-Thrombin
III Concentrate
·
Alpha
1-Proteinase Inhibitor Concentrate
Cryoprecipitated
AHF
Cryoprecipitated
Antihemophilic Factor (Cryo) is a portion of plasma rich in clotting factors,
including Factor VIII and fibrinogen. It is prepared by freezing and then
slowly thawing the frozen plasma.
Cryoprecipitated
Antihemophilic Factor (Cryo) is a portion of plasma rich in clotting factors,
including Factor VIII and fibrinogen. It is prepared by freezing and then
slowly thawing the frozen plasma.
White Blood
Cells & Granulocytes
White Blood
Cells
White blood
cells (leukocytes) are one of the body’s defenses against disease. Some white
cells travel throughout the body and destroy bacteria, some produce antibodies
against bacteria and viruses, and others help fight malignant diseases. One’s
own “leukocytes” help maintain the body’s immune function, but when present in
donated blood, they serve no purpose. In fact, leukocytes may carry viruses
that cause immune suppression and release toxic substances in the recipient.
Leukocytes can cause a reaction when transfused, and are often removed from the
transfusable blood components, a process called leuko-reduction. The majority
of white blood cells are produced in the bone marrow, where they outnumber red
blood cells by 2 to 1. However, in the blood stream, there are about 600 red
blood cells for every white blood cell. There are several different types of
white blood cells.
Granulocytes
Granulocytes
are one type of several types of white blood cells that are in fact used in
more specialized transfusion therapy. Granulocytes and monocytes protect
against infection by surrounding and destroying invading bacteria and viruses,
and lymphocytes aid in the immune defense system. Granulocytes are prepared by
an automated process called apheresis, and must be transfused within 24 hours
after collection. They are used for infections that are unresponsive to
antibiotic therapy.
Leukemia
or leukaemia
(see spelling
differences) is a cancer
of the blood
or bone
marrow and is characterized by an abnormal proliferation (production by
multiplication) of blood cells,
usually white blood cells (leukocytes).
It is part of the broad group of diseases called hematological
neoplasms.
Damage to the bone marrow, by way of displacing the normal
bone marrow cells with higher numbers of immature white blood cells, results in
a lack of blood platelets,
which are important in the blood
clotting process. This means people with leukemia may become bruised,
bleed
excessively, or develop pinprick bleeds (petechiae).
White
blood cells, which are involved in fighting pathogens,
may be suppressed or dysfunctional, putting the patient at the risk of
developing infections.
Finally, the red
blood cell deficiency leads to anemia,
which may cause dyspnea.
All symptoms may also be attributable to other diseases; for diagnosis,
blood
tests and a bone
marrow examination are required.
Some other related symptoms
·
Fever, chills, and other flu-like symptoms
·
Weakness and fatigue
·
Loss of appetite
and/or weight
·
Swollen or
bleeding gums
·
Neurological
symptoms (headache)
·
Enlarged liver
and spleen
Leukemia is a broad term
covering a spectrum of diseases.
Definition: condition in which
the bone marrow has an abnormally high number of cancerous white blood cells,
which are not entering the bloodstream. Aleukemia occurs in about 30% of all
patients with leukemia, regardless of the specific type. When a patient is
aleukemic, the leukemia is not behaving in the usual way, i.e., with an
overwhelming number of early white blood cells in the blood. A person with
aleukemia will have a normal or low white blood count and bone marrow disorder.
Leukemia is clinically and
pathologically split into its acute
and chronic
forms.
·
Acute leukemia is characterized by the rapid
growth of immature blood cells. This crowding makes the bone marrow unable to
produce healthy blood cells. Acute forms of leukemia can occur in children and
young adults. (In fact, it is a more common cause of death for children in the US
than any other type of malignant disease.) Immediate treatment is required in
acute leukemias due to the rapid progression and accumulation of the malignant
cells, which then spill over into the bloodstream and spread to other organs of
the body. If left untreated, the patient will die within months or even weeks.
·
Chronic leukemia
is distinguished by the excessive build up of relatively mature, but still
abnormal, blood cells. Typically taking months to years to progress, the cells
are produced at a much higher rate than normal cells, resulting in many
abnormal white blood cells in the blood. Chronic leukemia mostly occurs in
older people, but can theoretically occur in any age group. Whereas acute leukemia
must be treated immediately, chronic forms are sometimes monitored for some
time before treatment to ensure maximum effectiveness of therapy.
There is no single
known cause for all of the different types of leukemia. The different leukemias
likely have different causes, and very little is certain about what causes them.
Researchers have strong suspicions about four possible causes:
·
natural or
artificial ionizing radiation
·
certain kinds of
chemicals
·
some viruses
·
genetic
predispositions
Leukemia, like
other cancers, result from somatic
mutations in the DNA
which activate oncogenes
or deactivate tumor
suppressor genes, and disrupt the regulation of cell death,
differentiation or division. These mutations may occur spontaneously or as a
result of exposure to radiation
or carcinogenic
substances and are likely to be influenced by genetic factors. Cohort and
case-control studies have linked exposure to petrochemicals,
such as benzene,
and hair
dyes to the development of some forms of leukemia.
Viruses
have also been linked to some forms of leukemia. For example, certain cases of
ALL are associated with viral infections by either the human
immunodeficiency virus (HIV, responsible for AIDS)
or human
T-lymphotropic virus (HTLV-1 and -2, causing adult
T-cell leukemia/lymphoma).
Fanconi
anemia is also a risk factor for developing acute
myelogenous leukemia.
Until the cause or causes of leukemia are found, there is
no way to prevent the disease.
It is most common for adults, but more men than women are
affected. Many different chemotherapeutic plans are available for the treatment
of AML. Overall, the strategy is to control bone marrow and systemic
(whole-body) disease while offering specific treatment for the central nervous
system (CNS), if involved. In general, most oncologists rely on combinations of
drugs for the initial, induction phase of chemotherapy. Such combination
chemotherapy usually offers the benefits of early remission (lessening of the
disease) and a lower risk of disease resistance. Consolidation or
"maintenance" treatments may be given to prevent disease recurrence
once remission has been achieved. Consolidation treatment often entails a
repetition of induction chemotherapy or the intensification chemotherapy with
added drugs. By contrast, maintenance treatment involves drug doses that are
lower than those administered during the induction phase.
In addition, specific treatment plans may be used,
depending on the type of leukemia that has been diagnosed. Whatever the plan,
it is important for the patient to understand the treatment that is being given
and the decision-making process behind the choice.
Initial treatment of AML usually begins with induction
chemotherapy using a combination of drugs such as daunorubicin (DNR),
cytarabine (ara-C), idarubicin, thioguanine, etoposide, or mitoxantrone.
Follow-up therapy for such patients may involve:
·
supportive care, such as intravenous nutrition and
treatment with oral antibiotics (e.g., ofloxacin, rifampin), especially in
patients who have prolonged granulocytopenia; that is too few mature
granulocytes (neutrophils), the bacteria-destroying white blood cells that
contain small particles, or granules (< 100 granulocytes per cubic
millimeter for 2 weeks)
·
injection with colony-stimulating factors such as
granulocyte colony-stimulating factor (G-CSF), which may help to shorten the
period of granulocytopenia that results from induction therapy
·
transfusions with red blood cells and platelets
Patients with newly diagnosed disease also may be
considered for stem cell transplantation (SCT), either from the bone marrow or
other sources. Allogeneic bone marrow transplant (alloBMT) is reserved
primarily for patients under 55 years of age who have a compatible family
donor. Approximately half of newly diagnosed AML patients are in this age
group, with 75% achieving a complete remission (CR) after induction and
consolidation therapy. Allogeneic bone marrow transplant is available for about
15% of all patients with AML. Unfortunately, it is estimated that only 7% of
all AML patients will be cured using this procedure.
People who receive stem cell transplantation (SCT,
alloBMT) require protective isolation in the hospital, including filtered air,
sterile food, and sterilization of the microorganisms in the gut, until their
total white blood cell (WBC) count is above 500.
Treatment of central nervous system leukemia, if present,
may involve injection of chemotherapeutic drugs (e.g., cytarabine or ara-C,
methotrexate) into the areas around the brain and spinal cord.
Once the patient is in remission, he or she will receive
consolidation or maintenance therapy, for example, consolidation therapy with
high-dose ara-C (HDAC) with/without anthracycline drugs).
If, however, the AML patient has resistant disease (about
15%) or relapses (about 70%), second remissions sometimes are achieved by
treating them with:
·
conventional induction chemotherapy
·
high-dose ara-C (HDAC), with/without other drugs
·
etoposide or other single chemotherapeutic agents
Elderly AML patients have special treatment concerns. They
may be less able to tolerate the septicemia (blood poisoning) associated with
granulocytopenia, and they often have higher rates of myelodysplastic
('preleukemia') syndrome (MDS). Individuals who are over age 75 or who have
significant medical conditions can be treated effectively with low-dose ara-C.
High-dose post-induction chemotherapy is unlikely to be tolerated by elderly
patients.
Until recently, the treatment plans and responses of
children with AML did not differ much from those of adults. Yet new, more
intensive induction and consolidation treatments have resulted in higher
remission rates and prolonged survivals. Many induction trials have produced
good results using combinations of cytarabine (ara-C) plus an anthracycline
(e.g., daunorubicin, doxorubicin). In children under 3 years of age, the
anthracycline used for induction should be chosen with care, since doxorubicin
produces more toxicity and related deaths than daunorubicin.
Consolidation therapy is complex, but it should include at
least two courses of high-dose ara-C (HDAC). Children who have hyperleukocytosis
(too many white blood cells), especially monocytic M5 leukemia, have a poor
prognosis.
Leukemia (American English) or leukaemia (British
English) (from the Ancient Greek λευκός leukos
"white", and αἷμα haima
"blood") is a type of cancer of the blood or bone marrow
characterized by an abnormal increase of immature white blood cells called
"blasts." Leukemia is a broad term covering a spectrum of diseases. In
turn, it is part of the even broader group of diseases affecting the blood,
bone marrow, and lymphoid system, which are all known as hematological
neoplasms.
In 2000, approximately 256,000 children and adults
around the world developed some form of leukemia, and 209,000 died from it.
About 90% of all leukemias are diagnosed in adults.
Classification
Four major kinds of leukemia
1.
Cell type: Lymphocytic leukemia(or
"lymphoblastic"), Myelogenous leukemia (also "myeloid" or
"nonlymphocytic")
2.
Acute: Acute
lymphoblastic leukemia (ALL), Acute myelogenous leukemia (AML) Acute lymphoblastic leukemia (ALL) (or myeloblastic)
3.
Chronic: Chronic lymphocytic leukemia (CLL), Chronic
myelogenous leukemia (CML)
Clinically and pathologically, leukemia is subdivided
into a variety of large groups. The first division is between its acute and
chronic forms:
Acute leukemia is characterized by a rapid increase
in the number of immature blood cells. Crowding due to such cells makes the
bone marrow unable to produce healthy blood cells. Immediate treatment is
required in acute leukemia due to the rapid progression and accumulation of the
malignant cells, which then spill over into the bloodstream and spread to other
organs of the body. Acute forms of leukemia are the most common forms of
leukemia in children
Chronic leukemia is characterized by the excessive
build up of relatively mature, but still abnormal, white blood cells. Typically
taking months or years to progress, the cells are produced at a much higher
rate than normal, resulting in many abnormal white blood cells. Whereas acute
leukemia must be treated immediately, chronic forms are sometimes monitored for
some time before treatment to ensure maximum effectiveness of therapy. Chronic
leukemia mostly occurs in older people, but can theoretically occur in any age
group.
Additionally, the diseases are subdivided according
to which kind of blood cell is affected. This split divides leukemias into
lymphoblastic or lymphocytic leukemias and myeloid or myelogenous leukemias:
In lymphoblastic or lymphocytic leukemias, the
cancerous change takes place in a type of marrow cell that normally goes on to
form lymphocytes, which are infection-fighting immune system cells. Most
lymphocytic leukemias involve a specific subtype of lymphocyte, the B cell.
In myeloid or myelogenous leukemias, the cancerous
change takes place in a type of marrow cell that normally goes on to form red
blood cells, some other types of white cells, and platelets.
Combining these two classifications provides a total
of four main categories. Within each of these four main categories, there are
typically several subcategories. Finally, some rarer types are usually
considered to be outside of this classification scheme.
Acute lymphoblastic leukemia (ALL) is the most common
type of leukemia in young children. This disease also affects adults,
especially those age 65 and older. Standard treatments involve chemotherapy and
radiotherapy. The survival rates vary by age: 85% in children and 50% in
adults. Subtypes include precursor B acute lymphoblastic leukemia, precursor T
acute lymphoblastic leukemia, Burkitt's leukemia, and acute biphenotypic
leukemia.
Chronic lymphocytic leukemia (CLL) most often affects
adults over the age of 55. It sometimes occurs in younger adults, but it almost
never affects children. Two-thirds of affected people are men. The five-year
survival rate is 75%. It is incurable, but there are many effective treatments.
One subtype is B-cell prolymphocytic leukemia, a more aggressive disease.
Acute myelogenous leukemia (AML) occurs more commonly
in adults than in children, and more commonly in men than women. AML is treated
with chemotherapy. The five-year survival rate is 40%. Subtypes of AML include
acute promyelocytic leukemia, acute myeloblastic leukemia, and acute
megakaryoblastic leukemia.
Chronic myelogenous leukemia (CML) occurs mainly in
adults; a very small number of children also develop this disease. Treatment is
with imatinib (Gleevec in US, Glivec in Europe)
or other drugs. The five-year survival rate is 90%. One subtype is
chronic monocytic leukemia.
Hairy cell leukemia (HCL) is sometimes considered a
subset of chronic lymphocytic leukemia, but does not fit neatly into this
pattern. About 80% of affected people are adult men. No cases in children have
been reported. HCL is incurable, but easily treatable. Survival is 96% to 100%
at ten years.
T-cell prolymphocytic leukemia (T-PLL) is a very rare
and aggressive leukemia affecting adults; somewhat more men than women are
diagnosed with this disease. Despite its overall rarity, it is also the most
common type of mature T cell leukemia; nearly all other leukemias involve B
cells. It is difficult to treat, and the median survival is measured in months.
Large granular lymphocytic leukemia may involve
either T-cells or NK cells; like hairy cell leukemia, which involves solely B
cells, it is a rare and indolent (not aggressive) leukemia. Adult T-cell
leukemia is caused by human T-lymphotropic virus (HTLV), a virus similar to
HIV. Like HIV, HTLV infects CD4+ T-cells and replicates within them; however,
unlike HIV, it does not destroy them. Instead, HTLV "immortalizes"
the infected T-cells, giving them the ability to proliferate abnormally. Human
T cell lymphotropic virus types I and II (HTLV-I/II) are endemic in certain
areas of the world.
Signs and symptoms
Common symptoms of chronic or acute leukemia
Damage to the bone marrow, by way of displacing the
normal bone marrow cells with higher numbers of immature white blood cells,
results in a lack of blood platelets, which are important in the blood clotting
process. This means people with leukemia may easily become bruised, bleed
excessively, or develop pinprick bleeds (petechiae).
White blood cells, which are involved in fighting
pathogens, may be suppressed or dysfunctional. This could cause the patient's
immune system to be unable to fight off a simple infection or to start
attacking other body cells. Because leukemia prevents the immune system from
working normally, some patients experience frequent infection, ranging from infected
tonsils, sores in the mouth, or diarrhea to life-threatening pneumonia or
opportunistic infections.
Finally, the red blood cell deficiency leads to
anemia, which may cause dyspnea and pallor.
Some patients experience other symptoms, such as
feeling sick, having fevers, chills, night sweats, feeling fatigued and other
flu-like symptoms. Some patients experience nausea or a feeling of fullness due
to an enlarged liver and spleen; this can result in unintentional weight loss.
Blasts affected by the disease may come together and become swollen in the
liver or in the lymph nodes causing pain and leading to nausea.
If the leukemic cells invade the central nervous
system, then neurological symptoms (notably headaches) can occur. All symptoms
associated with leukemia can be attributed to other diseases. Consequently,
leukemia is always diagnosed through medical tests.
The word leukemia, which means 'white blood', is
derived from the disease's namesake high white blood cell counts that most
leukemia patients have before treatment. The high number of white blood cells
are apparent when a blood sample is viewed under a microscope. Frequently,
these extra white blood cells are immature or dysfunctional. The excessive
number of cells can also interfere with the level of other cells, causing a
harmful imbalance in the blood count.
Some leukemia patients do not have high white blood
cell counts visible during a regular blood count. This less-common condition is
called aleukemia. The bone marrow still contains cancerous white blood cells
which disrupt the normal production of blood cells, but they remain in the
marrow instead of entering the bloodstream, where they would be visible in a
blood test. For an aleukemic patient, the white blood cell counts in the
bloodstream can be normal or low. Aleukemia can occur in any of the four major
types of leukemia, and is particularly common in hairy cell leukemia.
Causes
No single known cause for any of the different types
of leukemia exists. The known causes, which are not generally factors within
the control of the average person, account for relatively few cases. The
different leukemias likely have different causes.
Leukemia, like other cancers, results from mutations
in the DNA. Certain mutations can trigger leukemia by activating oncogenes or
deactivating tumor suppressor genes, and thereby disrupting the regulation of
cell death, differentiation or division. These mutations may occur
spontaneously or as a result of exposure to radiation or carcinogenic
substances.
Among adults, the known causes are natural and
artificial ionizing radiation, a few viruses such as human T-lymphotropic
virus, and some chemicals, notably benzene and alkylating chemotherapy agents
for previous malignancies. Use of tobacco is associated with a small increase
in the risk of developing acute myeloid leukemia in adults. Cohort and
case-control studies have linked exposure to some petrochemicals and hair dyes
to the development of some forms of leukemia. A few cases of maternal-fetal
transmission have been reported. Diet has very limited or no effect, although
eating more vegetables may confer a small protective benefit.
Viruses have also been linked to some forms of
leukemia. Experiments on mice and other mammals have demonstrated the relevance
of retroviruses in leukemia, and human retroviruses have also been identified.
The first human retrovirus identified was human T-lymphotropic virus, or
HTLV-1, which is known to cause adult T-cell leukemia.
Some people have a genetic predisposition towards
developing leukemia. This predisposition is demonstrated by family histories
and twin studies. The affected people may have a single gene or multiple genes
in common. In some cases, families tend to develop the same kinds of leukemia
as other members; in other families, affected people may develop different
forms of leukemia or related blood cancers.
In addition to these genetic issues, people with
chromosomal abnormalities or certain other genetic conditions have a greater
risk of leukemia. For example, people with Down syndrome have a significantly
increased risk of developing forms of acute leukemia (especially acute myeloid
leukemia), and Fanconi anemia is a risk factor for developing acute myeloid
leukemia.
Whether non-ionizing radiation causes leukemia has
been studied for several decades. The International Agency for Research on
Cancer expert working group undertook a detailed review of all data on static
and extremely low frequency electromagnetic energy, which occurs naturally and
in association with the generation, transmission, and use of electrical power.
They concluded that there is limited evidence that high levels of ELF magnetic
(but not electric) fields might cause childhood leukemia. Exposure to significant
ELF magnetic fields might result in twofold excess risk for leukemia for
children exposed to these high levels of magnetic fields. However, the report
also says that methodological weaknesses and biases in these studies have
likely caused the risk to be overstated. No evidence for a relationship to
leukemia or another form of malignancy in adults has been demonstrated. Since
exposure to such levels of ELFs is relatively uncommon, the World Health
Organization concludes that ELF exposure, if later proven to be causative,
would account for just 100 to 2400 cases worldwide each year, representing 0.2
to 4.9% of the total incidence of childhood leukemia for that year (about 0.03
to 0.9% of all leukemias).
According to a study conducted at the Center for
Research in Epidemiology and Population Health in France, children born to
mothers who use fertility drugs to induce ovulation are more than twice as
likely to develop leukemia during their childhoods than other children.
Race is known to play a role, with some racial groups
being more at risk than others. Hispanics, especially those under the age of
20, are at the highest risk for leukemia, while whites, Native Americans,
Asians, and Alaska Natives are at higher risk than blacks.
In the case of gender, more men than women are
diagnosed with leukemia and die from the disease. Around 31 percent more men
than women live with leukemia.
Diagnosis
Diagnosis is usually based on repeated complete blood
counts and a bone marrow examination following observations of the symptoms,
however, in rare cases blood tests may not show if a patient has leukemia,
usually this is because the leukemia is in the early stages or has entered
remission. A lymph node biopsy can be performed as well in order to diagnose
certain types of leukemia in certain situations.
Following diagnosis, blood chemistry tests can be
used to determine the degree of liver and kidney damage or the effects of
chemotherapy on the patient. When concerns arise about visible damage due to
leukemia, doctors may use an X-ray, MRI, or ultrasound. These can potentially
view leukemia's effects on such body parts as bones (X-ray), the brain (MRI),
or the kidneys, spleen, and liver (ultrasound). Finally, CT scans are rarely
used to check lymph nodes in the chest.
Despite the use of these methods to diagnose whether
or not a patient has leukemia, many people have not been diagnosed because many
of the symptoms are vague, unspecific, and can refer to other diseases. For
this reason, the American Cancer Society predicts that at least one-fifth of
the people with leukemia have not yet been diagnosed.
Mutation in SPRED1 gene has been associated with a
predisposition to childhood leukemia. SPRED1 gene mutations can be diagnosed
with genetic sequencing.
Treatment
Most forms of leukemia are treated with
pharmaceutical medication, typically combined into a multi-drug chemotherapy
regimen. Some are also treated with radiation therapy. In some cases, a bone
marrow transplant is useful.
Acute lymphoblastic
Management of ALL focuses on control of bone marrow
and systemic (whole-body) disease. Additionally, treatment must prevent
leukemic cells from spreading to other sites, particularly the central nervous
system (CNS) e.g. monthly lumbar punctures. In general, ALL treatment is
divided into several phases:
Induction chemotherapy to bring about bone marrow
remission. For adults, standard induction plans include prednisone,
vincristine, and an anthracycline drug; other drug plans may include
L-asparaginase or cyclophosphamide. For children with low-risk ALL, standard
therapy usually consists of three drugs (prednisone, L-asparaginase, and
vincristine) for the first month of treatment.
Consolidation therapy or intensification therapy to
eliminate any remaining leukemia cells. There are many different approaches to
consolidation, but it is typically a high-dose, multi-drug treatment that is
undertaken for a few months. Patients with low- to average-risk ALL receive
therapy with antimetabolite drugs such as methotrexate and 6-mercaptopurine
(6-MP). High-risk patients receive higher drug doses of these drugs, plus
additional drugs.
CNS prophylaxis (preventive therapy) to stop the
cancer from spreading to the brain and nervous system in high-risk patients.
Standard prophylaxis may include radiation of the head and/or drugs delivered
directly into the spine.
Maintenance treatments with chemotherapeutic drugs to
prevent disease recurrence once remission has been achieved. Maintenance
therapy usually involves lower drug doses, and may continue for up to three
years.
Alternatively, allogeneic bone marrow transplantation
may be appropriate for high-risk or relapsed patients.
New therapeutic strategies for the treatment of acute
lymphoblastic .
The hallmark of bone-marrow B-cell development is the
ordered rearrangement of gene segments that encode the variable portion of the
antibody molecule. DJH rearrangements initially occur in lymphoid progenitor
cells that express CD34, CD10 and weak CD19. Pseudo-light chains (LC) CD179a
and CD179b first appear in the cytoplasm of early pre-B (pro-B) cells that
harbour VDJH rearrangement. The pre-B stage is heralded by the functional VDJH
rearrangement (bold type), the appearance of cytoplasmic immunoglobulin (Ig) heavy chains, and the
movement of CD22 from the cytoplasm to the cell surface. The transitional pre-B
cell undergoes V to JK light-chain rearrangement, and displays surface pre-B-cell
receptors that are comprised of Ig complexed to LC and are non-convalently
bound to CD79a and CD79b (/LC/CD79). The mature naive B-cell with functional
light-chain rearrangement (bold type) is initiated with the movement of IgM to
the cell surface, fully expresses / or / B-cell receptor (a complex of
IgM–CD79a–CD79b), and loses terminal deoxynucleotidyl transferase (TDT). The
bone-marrow-derived T-cell precursor expresses CD34, CD7 and possibly CD2, and
has T-cell receptor , , and genes (TCRD, TCRG, TCRA and TCRB) in germline
configuration. The earliest cells committed to T-cell development, pre-T cells,
are found in the outer cortical areas of thymus and express CD34, CD7, CD1a,
CD2, cytoplasmic CD3 and TDT, but not CD4 or CD8 (they are double negative
because of the absence of CD4 and CD8 expression). As these cell mature, they
lose CD34 expression, begin to express CD4 and then CD8, and thereby become
double-positive T cells that are characterized by CD7, CD2, CD5, CD4 and CD8
expression and low levels of CD3. Productive rearrangement of TCRA results in
the production of TCR molecules, which combine with TCR proteins to form TCR,
which in turn combine with CD3 and move to the surface of double-positive T
cells. Cells with a functional receptor (TCR+, double-positive late cortical
thymocytes) move into the cortico–medullary junction, and undergo positive or
negative selection. Only about 2% of all double-positive cells survive and
proceed through a final step of differentiation into either CD4- or
CD8-positive T cells. Distinct gene-expression signatures are associated with
leukaemic cell samples with recognized stages of thymocyte differentiation:
LYL1+ corresponds to pre-T, HOX11+ corresponds to early cortical, and TAL1+
corresponds to late cortical
Chronic lymphocytic
Decision to treat
Pathogenesis to treatment of chronic lymphocytic
leukaemia
The B cell receptor (BCR) is composed of two
immunoglobulin (Ig) heavy and light chains (variable and constant regions), and
CD79a and CD79b, which contain an intracellular activation motif that transmits
signals to intracellular tyrosine kinases (for example, SYK and LYN). The
ability of these kinases to activate downstream pathways varies in chronic
lymphocytic leukaemia (CLL) subgroups and is correlated with Ig heavy chain
variable region (IGHV) mutational status, zeta-associated protein 70 (ZAP70)
and CD38 expression4, 40, 41. These pathways could be targeted by small
molecule inhibitors, the most promising of which might be SYK inhibitors. b |
Multiple epitopes on the CLL cell are targets for antibody (ab)-based
therapies. c | The most common genetic lesions in CLL include deletion of 13q14
and the downregulation of death-associated protein kinase 1 (DAPK1, a
stress-activated tumour suppressor protein18, 99) by DNA methylation18. miR-15a
and miR-16-1 (encoded by genes located on 13q14) have been shown to target
BCL2, and may increase its expression in CLL143. This pathway can be targeted
at multiple levels, including through using small molecule BH3 mimetics136. d |
Stromal and T cell interactions also contribute to CLL pathogenesis. Although
not fully understood, some drugs (immune-modulating drugs; Imids) in use in CLL
have been shown to target the interaction with T cells109. The crosstalk
between CLL cells and accessory cells and soluble factors upregulates
anti-apoptotic proteins, such as survivin, MCL1 and BCL2 (Refs 103, 105, 106,
144). Ag, antigen; BLNK, B cell linker protein; BTK, Bruton tyrosine kinase;
CDK, cyclin-dependent kinase; CXCR4, chemokine receptor 4; HDAC, histone
deacetylase; IL-4, interleukin 4; Me, methyl group; NF-κB, nuclear
factor-κB; NFAT, nuclear factor of activated T cells; PLC-γ, phospholipase
C-γ; SDF1, stromal cell-derived factor 1;VEGFA, vascular endothelial
growth factor A.
Hematologists base CLL treatment on both the stage
and symptoms of the individual patient. A large group of CLL patients have
low-grade disease, which does not benefit from treatment. Individuals with
CLL-related complications or more advanced disease often benefit from
treatment. In general, the indications for treatment are:
Falling hemoglobin or platelet count
Progression to a later stage of disease
Painful, disease-related overgrowth of lymph nodes or
spleen
An increase in the rate of lymphocyte production
Objective: Studies concerning the genetic relatedness
between chronic lymphocytic leukemia and the more aggressive B-cell cancers
that develop in about 10% of affected persons were reviewed. These B-cell
cancers include large B-cell lymphoma (the Richter syndrome), prolymphocytic
transformation, acute lymphoblastic leukemia, and multiple myeloma. Two
possible relations were evaluated: development from the chronic lymphocytic
leukemia clone (clonal evolution) and development of a genetically unrelated,
independent second cancer.
Data Analysis: Analysis of genetic relatedness
between the two cancers considered concordance for immunoglobulin gene
rearrangements, for immunoglobulin isotypes and idiotypes, and for cytogenetic
abnormalities.
Conclusions: In the case of large B-cell lymphoma,
generally thought to arise from the chronic lymphocytic leukemia clone,
approximately one half of the patients had genetically unrelated cancers. In
prolymphocytic transformation, all cases studied appeared to evolve from the
chronic lymphocytic leukemia clone. The few studies of acute lymphoblastic
leukemia and multiple myeloma showed genetic relatedness in some cases and
unrelatedness in others. These data indicate that progression to more
aggressive B-cell cancers in persons with chronic lymphocytic leukemia can
result from either clonal evolution or from an independent transforming event.
Transformation of one B cell to produce chronic
lymphocytic leukemia is shown. Clonality is confirmed by analysis of
immunoglobulin genes (Southern blotting), antibodies (anti-isotypic and
anti-idiotypic), or chromosome analysis. The karyotype in the Figure shows a
trisomy 12, and the Southern blot shows the same germline in the normal ( ) and
the patient's ( ) peripheral blood cells (bar). A single immunoglobulin gene
rearrangement is identified in the patient's cells () but not in the normal
cells. Anti-idiotype antibodies are depicted as red with a green fluorescein
tag and show specific reactivity with the immunoglobulin on the chronic
lymphocytic leukemia cells. Determining genetic relatedness of the chronic
lymphocytic leukemia clone to large B-cell lymphoma, prolymphocytic
transformation, acute lymphoblastic leukemia, or multiple myeloma requires
reactivity with the same anti-idiotype antibody, showing identical
immunoglobulin gene rearrangements or identical karyotype.
Determining genetic relatedness of the chronic
lymphocytic leukemia
Typical treatment approach
CLL is probably incurable by present treatments. The primary
chemotherapeutic plan is combination chemotherapy with chlorambucil or
cyclophosphamide, plus a corticosteroid such as prednisone or prednisolone. The
use of a corticosteroid has the additional benefit of suppressing some related
autoimmune diseases, such as immunohemolytic anemia or immune-mediated
thrombocytopenia. In resistant cases, single-agent treatments with nucleoside
drugs such as fludarabine,pentostatin, or cladribine may be successful. Younger
patients may consider allogeneic or autologous bone marrow transplantation.
Acute myelogenous
Many different anti-cancer drugs are effective for
the treatment of AML. Treatments vary somewhat according to the age of the
patient and according to the specific subtype of AML. Overall, the strategy is
to control bone marrow and systemic (whole-body) disease, while offering
specific treatment for the central nervous system (CNS), if involved.
In general, most oncologists rely on combinations of
drugs for the initial, induction phase of chemotherapy. Such combination
chemotherapy usually offers the benefits of early remission and a lower risk of
disease resistance. Consolidation and maintenance treatments are intended to
prevent disease recurrence. Consolidation treatment often entails a repetition
of induction chemotherapy or the intensification chemotherapy with additional
drugs. By contrast, maintenance treatment involves drug doses that are lower
than those administered during the induction phase.
Chronic myelogenous
There are many possible treatments for CML, but the
standard of care for newly diagnosed patients is imatinib (Gleevec) therapy.
Compared to most anti-cancer drugs, it has relatively few side effects and can
be taken orally at home. With this drug, more than 90% of patients will be able
to keep the disease in check for at least five years, so that CML becomes a
chronic, manageable condition.
In a more advanced, uncontrolled state, when the
patient cannot tolerate imatinib, or if the patient wishes to attempt a
permanent cure, then an allogeneic bone marrow transplantation may be
performed. This procedure involves high-dose chemotherapy and radiation
followed by infusion of bone marrow from a compatible donor. Approximately 30%
of patients die from this procedure.
Hairy cell
Decision to treat
Patients with
hairy cell leukemia who are symptom-free typically do not receive immediate
treatment. Treatment is generally considered necessary when the patient shows
signs and symptoms such as low blood cell counts (e.g., infection-fighting
neutrophil count below 1.0 K/µL), frequent infections, unexplained bruises,
anemia, or fatigue that is significant enough to disrupt the patient's everyday
life.
Typical treatment approach
Patients who
need treatment usually receive either one week of cladribine, given daily by
intravenous infusion or a simple injection under the skin, or six months of
pentostatin, given every four weeks by intravenous infusion. In most cases, one
round of treatment will produce a prolonged remission.
Other treatments include rituximab infusion or
self-injection with Interferon-alpha. In limited cases, the patient may benefit
from splenectomy (removal of the spleen). These treatments are not typically
given as the first treatment because their success rates are lower than
cladribine or pentostatin.
T-cell prolymphocytic
Most patients with T-cell prolymphocytic leukemia, a
rare and aggressive leukemia with a median survival of less than one year,
require immediate treatment.
T-cell prolymphocytic leukemia is difficult to treat,
and it does not respond to most available chemotherapeutic drugs. Many
different treatments have been attempted, with limited success in certain
patients: purine analogues (pentostatin, fludarabine, cladribine),
chlorambucil, and various forms of combination chemotherapy (cyclophosphamide,
doxorubicin, vincristine, prednisone CHOP, cyclophosphamide, vincristine,
prednisone [COP], vincristine, doxorubicin, prednisone, etoposide,
cyclophosphamide, bleomycin VAPEC-B). Alemtuzumab (Campath), a monoclonal
antibody that attacks white blood cells, has been used in treatment with
greater success than previous options.
Some patients who successfully respond to treatment
also undergo stem cell transplantation to consolidate the response.
Juvenile myelomonocytic
Treatment for juvenile myelomonocytic leukemia can include
splenectomy, chemotherapy, and bone marrow transplantation.
Epidemiology
In 2000, approximately 256,000 children and adults
around the world developed a form of leukemia, and 209,000 died from it. This
represents about 3% of the almost seven million deaths due to cancer that year,
and about 0.35% of all deaths from any cause. Of the sixteen separate sites the
body compared, leukemia was the 12th most common class of neoplastic disease,
and the 11th most common cause of cancer-related death.
About 245,000 people in the United States are
affected with some form of leukemia, including those that have achieved
remission or cure. Approximately 44,270 new cases of leukemia were diagnosed in
the year of 2008 in the US.[40] This represents 2.9% of all cancers (excluding
simple basal cell and squamous cell skin cancers) in the United States, and
30.4% of all blood cancers.
Among children with some form of cancer, about a
third have a type of leukemia, most commonly acute lymphoblastic leukemia. A
type of leukemia is the second most common form of cancer in infants (under the
age of 12 months) and the most common form of cancer in older children. Boys
are somewhat more likely to develop leukemia than girls, and white American
children are almost twice as likely to develop leukemia than black American
children. Only about 3% cancer diagnoses among adults are for leukemias, but
because cancer is much more common among adults, more than 90% of all leukemias
are diagnosed in adults.
History
Leukemia was first observed by pathologist Rudolf
Virchow in 1845. Observing an abnormally large number of white blood cells in a
blood sample from a patient, Virchow called the condition Leukämie in
German, which he formed from the two Greek words leukos (λευκός), meaning "white", and
aima (αίμα), meaning
"blood". Around ten years after Virchow's findings, pathologist Franz
Ernst Christian Neumann found that one deceased leukemia patient's bone marrow
was colored "dirty green-yellow" as opposed to the normal red. This
finding allowed Neumann to conclude that a bone marrow problem was responsible
for the abnormal blood of leukemia patients.
By 1900 leukemia was viewed as a family of diseases
as opposed to a single disease. By 1947 Boston pathologist Sydney Farber
believed from past experiments that aminopterin, a folic acid mimic, could
potentially cure leukemia in children. The majority of the children with ALL
who were tested showed signs of improvement in their bone marrow, but none of
them were actually cured. This, however, led to further experiments.
In 1962, researchers Emil J. Freireich Jr. and Emil
Frei III used combination chemotherapy to attempt to cure leukemia. The tests
were successful with some patients surviving long after the tests.
Research directions
Significant research into the causes, prevalence,
diagnosis, treatment, and prognosis of leukemia is being performed. Hundreds of
clinical trials are being planned or conducted at any given time. Studies may
focus on effective means of treatment, better ways of treating the disease,
improving the quality of life for patients, or appropriate care in remission or
after cures.
In general, there are two types of leukemia research:
clinical or translational research and basic research. Clinical/translational
research focuses on studying the disease in a defined and generally immediately
patient-applicable way, such as testing a new drug in patients. By contrast,
basic science research studies the disease process at a distance, such as
seeing whether a suspected carcinogen can cause leukemic changes in isolated
cells in the laboratory or how the DNA changes inside leukemia cells as the
disease progresses. The results from basic research studies are generally less
immediately useful to patients with the disease.
Treatment through gene therapy is currently being
pursued. One such approach turns T cells into cancer-targeting attackers. As of
August 2011, a year after treatment, two of the three patients are cancer-free.
Society and culture
Leukemias are often romanticized in 20th century
fiction. It is presented as a pure, clean disease, whose innocent, beautiful,
and spiritually sensitive victims tragically die young. As such, it is the
cultural successor to tuberculosis, which held this cultural position until
tuberculosis was discovered to be an infectious disease. The 1970 romance novel
Love Story is an example of this romanticization of leukemia.
In pregnancy
Leukemia is rarely associated with pregnancy,
affecting only about 1 in 10,000 pregnant women. How it is handled depends
primarily on the type of leukemia. Nearly all leukemias appearing in pregnant
women are acute leukemias. Acute leukemias normally require prompt, aggressive
treatment, despite significant risks of pregnancy loss and birth defects,
especially if chemotherapy is given during the developmentally sensitive first
trimester. Chronic myelogenous leukemia can be treated with relative safety at
any time during pregnancy with Interferon-alpha hormones. Treatment for chronic
lymphocytic leukemias, which are rare in pregnant women, can often be postponed
until after the end of the pregnancy.
The occurrence of leukemia during pregnancy is very
rare with an estimated incidence of one per 100,000 pregnancies annually. It
has been estimated that during pregnancy most leukemias are acute: two thirds
are myeloid (AML) and one third are lymphatic (ALL). Chronic myeloid leukemia
(CML) is found in less than 10% of leukemias during pregnancy and chronic lymphocytic leukemia (CLL) is
extremely rare.
The survival of pregnant and non-pregnant women with
acute leukemia has improved with the availability of modern chemotherapy and
supportive care. Remission rates of 70-75% and median survival time of 6 to12
months are currently reported for pregnant women. These figures are not
different from those achieved in non-pregnant women with acute leukemia.
Acute leukemia can affect pregnancy and the fetus.
Intrauterine growth retardation has been reported in
mothers not treated with chemotherapy.
In addition, preterm labor, induced and spontaneous
abortion as well as still birth are common in acute leukemia.
Although there is an estimated teratogenic risk rate
of 10% when chemotherapy is administered in the first trimester, no fetal
malformations and no late side effects have been reported in children born to
mothers who were treated for acute leukemia during early pregnancy .
Pregnancy in Chronic Myeloid Leukemia
Treatment
It is generally believed that pregnant women should
be treated as non-pregnant women.
Therapeutic abortion should be considered in early
gestation, but if the woman decides to continue the pregnancy certain drugs,
like methotrexate, should be replaced. Standard anti-leukemic treatment can be
safely administered during the second and third trimesters. Delivery should be
accomplished when fetal survival can be ensured and the mother is in complete
remission. There are rare reports of leukemia blasts infiltrating the
placenta and a single case of infantile
acute monocytic leukemia caused by vertical transmission of the mother's
leukemia cells.
Five cases of
relapse of ALL in pregnancy have been reported in the medical literature. The mechanisms
attributable to the immunologic and hormonal changes of pregnancy have been
postulated. All five patients were treated between 2 weeks and 4.5 months with
cytotoxic chemotherapy with the fetus still in utero. Four out of five patients
delivered healthy and normal infants and an elective abortion was reported.
Unfortunately, all mothers except one died of their disease in under 2 years.
Chronic myeloid leukemia during pregnancy should be
treated as in the nongestational patients. Since the disease has an initial
chronic phase, it is usually managed conservatively during pregnancy, while an
aggressive approach, such as bone marrow transplantation, may be considered
after delivery. A limited number of cases described successful treatment
modalities of CML during pregnancy including leukapheresis, hydroxyurea and interferon.
Pregnancy complicated by hairy cell leukemia is
extremely rare. Splenectomy is a safe and effective treatment option during the
second trimester for this rare condition
Single cases have been treated with interferon during pregnancy.
Prevention
Folate supplements taken by pregnant women may also
protect babies from leukemia.
A new study, suggests that women who eat more vegetables,
fruit and foods containing protein before pregnancy may have a lower risk of
having a child who develops leukemia, the most common childhood cancer in the
United States.
The study, published in the August 2004 issue of
Cancer Causes and Control, is the first time researchers have conducted a
systematic survey of a woman's diet and linked it to childhood leukemia risk.
Within the fruit and vegetable food groups, certain
foods - including carrots, string beans and cantaloupe - stood out as having
stronger links to lower childhood leukemia risk. The researchers point to the
benefits of nutrients, such as carotenoids, in those foods as potential
protective factors.
The researchers looked further and found that
glutathione was the nutrient in the protein group with a strong link to lower
cancer risk. Glutathione is an antioxidant found in both meat and legumes, and
it plays a role in the synthesis and repair of DNA, as well as the
detoxification of certain harmful compounds. National guidelines recommend that
people eat at least five servings of fruits and vegetables every day, and two
to three servings of foods from the protein group.
B-cell chronic lymphocytic leukemia
Peripheral blood smear showing CLL cells
B-cell chronic lymphocytic leukemia (B-CLL), also
known as chronic lymphoid leukemia (CLL), is the most common type of leukemia.
Leukemias are cancers of the white blood cells (leukocytes). CLL affects B cell
lymphocytes. B cells originate in the bone marrow, develop in the lymph nodes,
and normally fight infection by producing antibodies. In CLL, B cells grow out
of control and accumulate in the bone marrow and blood, where they crowd out
healthy blood cells. CLL is a stage of small lymphocytic lymphoma (SLL), a type
of B-cell lymphoma, which presents primarily in the lymph nodes. CLL and SLL
are considered the same underlying disease, just with different appearances.
CLL is a disease of adults, but, in rare cases, it
can occur in teenagers and occasionally in children (inherited). Most (>75%)
people newly diagnosed with CLL are over the age of 50, and the majority are
men.
Most people are diagnosed without symptoms as the
result of a routine blood test that returns a high white blood cell count, but,
as it advances, CLL results in swollen lymph nodes, spleen, and liver, and
eventually anemia and infections. Early CLL is not treated, and late CLL is
treated with chemotherapy and monoclonal antibodies.
DNA analysis has distinguished two major types of
CLL, with different survival times. CLL that is positive for the marker ZAP-70
has an average survival of 8 years. CLL that is negative for ZAP-70 has an
average survival of more than 25 years. Many patients, especially older ones,
with slowly progressing disease can be reassured and may not need any treatment
in their lifetimes.
Symptoms and signs
Most people are diagnosed without symptoms as the
result of a routine blood test that returns a high white blood cell count. Less
commonly, CLL may present with enlarged lymph nodes without a high white blood
cell count or no evidence of the disease in the blood. This is referred to as
small lymphocytic lymphoma. In some individuals the disease comes to light only
after the neoplastic cells overwhelm the bone marrow resulting in anemia
producing tiredness or weakness.
Diagnosis
Micrograph of a lymph node affected by B-CLL showing
a characteristic proliferation center (right of image), composed of larger,
lighter staining, cells. H&E stain.
CLL is usually first suspected by the presence of a
lymphocytosis, an increase in one type of white blood cell, on a complete blood
count (CBC) test. This frequently is an incidental finding on a routine
physician visit. Most often the lymphocyte count is greater than 4000 cells per
microliter (µl) of blood, but can be much higher. The presence of a
lymphocytosis in an elderly individual should raise strong suspicion for CLL,
and a confirmatory diagnostic test, in particular flow cytometry, should be
performed unless clinically unnecessary.
The diagnosis of CLL is based on the demonstration of
an abnormal population of B lymphocytes in the blood, bone marrow, or tissues
that display an unusual but characteristic pattern of molecules on the cell
surface. This atypical molecular pattern includes the coexpression of cells
surface markers cluster of differentiation 5 (CD5) and cluster of
differentiation 23 (CD23). In addition, all the CLL cells within one individual
are clonal, that is, genetically identical. In practice, this is inferred by
the detection of only one of the mutually exclusive antibody light chains,
kappa or lambda, on the entire population of the abnormal B cells. Normal B
lymphocytes consist of a stew of different antibody-producing cells, resulting
in a mixture of both kappa and lambda expressing cells. The lack of the normal
distribution of kappa and lambda producing B cells is one basis for
demonstrating clonality, the key element for establishing a diagnosis of any B
cell malignancy (B cell non-Hodgkin lymphoma).
The combination of the microscopic examination of the
peripheral blood and analysis of the lymphocytes by flow cytometry to confirm
clonality and marker molecule expression is needed to establish the diagnosis
of CLL. Both are easily accomplished on a small amount of blood. A flow
cytometer is an instrument that can examine the expression of molecules on
individual cells in fluids. This requires the use of specific antibodies to
marker molecules with fluorescent tags recognized by the instrument. In CLL,
the lymphocytes are genetically clonal, of the B cell lineage (expressing
marker molecules cluster of differentiation 19 (CD19) and CD20), and
characteristically express the marker molecules CD5 and CD23. These B cells
resemble normal lymphocytes under the microscope, although slightly smaller,
and are fragile when smeared onto a glass slide, giving rise to many broken
cells, which are called smudge, or smear cells.
Childhood leukemia, the most
common type of cancer in children and teens, is a cancer
of the white blood cells. Abnormal white blood cells
form in the bone marrow. They quickly travel through the bloodstream and crowd
out healthy cells. This increases the body's chances of infection and other
problems.
As tough as it
is for a child to have cancer, it's good to know that most children and teens
with childhood leukemia can be successfully treated.
Description of Evidence
Incidence and
Mortality An estimated 12,200 new cervical cancers and 4,210 cervical cancer
deaths will occur in the United States in 2010.An additional 1,250,000 women
will be diagnosed with precancers annually by cytology using the Papanicolaou
(Pap) smear. A continuum of pathologic changes may be diagnosed, ranging from atypical
squamous cells of undetermined significance to low-grade squamous
intraepithelial lesions (LSIL) to high-grade squamous intraepithelial lesions
(HSIL) to invasive...
Doctors don't
know exactly what causes most cases of childhood leukemia. But certain factors
may increase the chances of getting it. Keep in mind, though, that having a
risk factor does not necessarily mean a child will get leukemia. In fact, most
children with leukemia don't have any known risk factors.
The risk for
childhood leukemia increases if your child has:
·
An inherited
disorder such as Li-Fraumeni syndrome, Down syndrome, or
Klinefelter syndrome
·
An inherited
immune system problem such as ataxia telangiectasia
·
A brother or
sister with leukemia, especially an identical twin
·
A history of
being exposed to high levels of radiation, chemotherapy, or
chemicals such as benzene (a solvent)
·
A history of
immune system suppression, such as for an organ transplant
Although the
risk is small, doctors advise that children with known risk factors have
regular checkups to spot any problems early.
Almost all
cases of childhood leukemia are acute, which means they develop rapidly. A tiny
number are chronic and develop slowly.
Types of
childhood leukemia include:
·
Acute lymphoblastic leukemia (ALL), also called acute lymphocytic leukemia. ALL
accounts for three out of every four cases of childhood leukemia.
·
Acute
myelogenous leukemia (AML). AML is the next most common type of childhood
leukemia.
·
Hybrid or
mixed lineage leukemia. This is a rare leukemia with features of both ALL and
AML.
·
Chronic
myelogenous leukemia (CML). CML is rare in children.
·
Chronic
lymphocytic leukemia (CLL). CLL is very rare in children.
·
Juvenile
myelomonocytic leukemia (JMML). This is a rare type that is neither chronic nor
acute and occurs most often in children under age 4.
Symptoms of
leukemia often prompt a visit to the doctor. This is a good thing because it
means the disease may be found earlier than it otherwise would. Early diagnosis
can lead to more successful treatment.
Many signs
and symptoms of childhood leukemia occur when leukemia cells crowd out normal
cells.
Common
symptoms include:
·
Fatigue or pale skin
·
Infections
and fever
·
Easy bleeding
or bruising
·
Extreme
fatigue or weakness
·
Shortness of
breath
·
Coughing
Other
symptoms may include:
·
Bone or joint
pain
·
Swelling in
the abdomen, face, arms,
underarms, sides of neck, or groin
·
Swelling
above the collarbone
·
Loss of
appetite or weight loss
·
Headaches,
seizures, balance problems, or abnormal vision
·
Vomiting
·
Rashes
·
Gum problems
To diagnose
childhood leukemia, the doctor will take a thorough medical history and perform
a physical exam. Tests are
used to diagnose childhood leukemia as well as classify its type.
Initial tests
may include:
·
Blood tests to
measure the number of blood cells and see how they appear.
·
Bone marrow
aspiration and biopsy, usually
taken from the pelvic bone, to confirm a diagnosis of leukemia.
·
Lumbar puncture, or spinal tap, to
check for spread of leukemia cells in the fluid that bathes the brain and spinal cord.
A pathologist examines cells from the
blood tests under a microscope. This specialist also checks bone marrow samples
for the number of blood-forming cells and fat cells.
Other tests may be done to help
determine which type of leukemia your child may have. These tests also help the
doctors know how likely the leukemia is to respond to treatment.
Certain tests may be repeated later
to see how your child responds to treatment.
Have a "heart-to-heart"
talk with your child's doctor and other members of the cancer care team about
the best options for your child. Treatment depends mainly upon the type of
leukemia as well as other factors.
The good news is the survival rates
for most types of childhood leukemia have increased over time. And treatment at
special centers for children and teens provides the advantages of specialized
care. In addition, childhood cancers tend to respond to treatment better than
adult cancers do, and children's bodies often tolerate treatment better.
Before cancer treatment begins,
sometimes a child needs treatment to address illness complications. For
example, changes in blood cells can lead to infections or severe bleeding and
may affect the amount of oxygen reaching the body's tissues. Treatment may
involve antibiotics, blood transfusions, or other measures to fight infection.
Chemotherapy is the main treatment
for childhood leukemia. Your child will receive anticancer drugs by mouth, or into a vein, a muscle,
or the spinal fluid. To keep leukemia from returning, maintenance therapy
occurs in cycles over a period of two or three years.
Targeted therapy is also sometimes
used for leukemia. This therapy targets specific parts of cancer cells, working
differently than standard chemotherapy. Effective for certain types of
childhood leukemia, targeted therapy often has less severe side effects.
Other types of treatment may include
radiation therapy, which uses high-energy radiation to kill cancer cells and
shrink tumors. It may be used to help prevent or treat the spread of leukemia
to other parts of the body. Surgery is rarely used to treat childhood leukemia.
If standard treatment is likely to be
less effective, a stem cell transplant may be the best option. It involves a
transplant of blood-forming stem cells after whole body radiation combined with
high-dose chemotherapy to first destroy the child's bone marrow.
VIDEO
Blood
Groups
Diseases
of Blood
Literature:
1. Àäàì÷èê Ì.Â.
Âåëèêèé àíãëî-óêðà¿íñüêèé ñëîâíèê. – Êè¿â, 2007.
2. Àíãë³éñüêà
ìîâà çà ïðîôåñ³éíèì ñïðÿìóâàííÿì: Ìåäèöèíà: íàâ÷. ïîñ³á. äëÿ ñòóä. âèù. íàâ÷.
çàêë. IV ð³âíÿ àêðåäèòàö³¿ / ². À. Ïðîêîï, Â. ß. Ðàõëåöüêà, Ã. ß. Ïàâëèøèí ;
Òåðíîï. äåðæ. ìåä. óí-ò ³ì. ². ß. Ãîðáà÷åâñüêîãî. – Òåðíîï³ëü: ÒÄÌÓ : Óêðìåäêíèãà, 2010. – 576 ñ.
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