Hematology PPT Flashcards Unit 2
What is the shape of a mature
erythrocyte?
The mature erythrocyte is a biconcave disc with a
central pallor that occupies the middle one third of
the cell.
What is the function of hemoglobin in
In the mature cell, the respiratory protein,
the mature cell?
hemoglobin, performs the function of oxygen–carbon
dioxide transport.
What is the lifespan of a mature
Throughout the life span of the mature cell, an
erythrocyte?
average of 120 days, this soft and pliable cell moves
with ease through the tissue capillaries and splenic
circulation.
What changes the cell go through as it
As the cell ages, cytoplasmic enzymes are
ages?
catabolized, leading to increased membrane rigidity
(density), phagocytosis, and destruction.
What is erythropoiesis?
The term used to describe the process of erythrocyte
production is erythropoiesis.
What does erythropoiesis encompass?
Erythropoiesis encompasses differentiation from the
hematopoietic stem cell (HSC) through the mature
erythrocyte.
How is the transport of oxygen and
Transport of oxygen to the tissues and transport of
carbon dioxide accomplished?
carbon dioxide from the tissues is accomplished by
the heme pigment in hemoglobin, which is
synthesized as the erythrocyte matures.
What are the basic substances which are The basic substances needed for normal erythrocyte
needed for a mature erythrocyte?
and hemoglobin production are amino acids
(proteins), iron, vitamin B12, vitamin B6, folic acid
(a member of the vitamin B2 complex), and the trace
minerals cobalt and nickel.
What happens when there are not enough Abnormal erythropoiesis can result from deficiencies
of these substances?
of any of these necessary substances.
Which organ makes erythropoietin?
Erythropoietin is produced primarily by the kidneys.
How are tissue oxygenation and blood
Blood levels of erythropoietin are inversely related to
erythropoietin related?
tissue oxygenation.
What are the effects of erythropoietin?
Erythropoietin produces an increase in the production
of several types of ribonucleic acid (RNA) followed
by an increase in deoxyribonucleic acid (DNA)
activity and protein synthesis.
How long time does the erythroid cell
Once the stem cell differentiates into the erythroid
spend in the nucleated cell stage?
cell line, a cell matures through the nucleated cell
stages in 4 or 5 days.
How long is the average maturation
Bone marrow reticulocytes have an average
period for a bone marrow reticulocyte?
maturation period of 2.5 days.
How long do the young reticulocytes
Once young reticulocytes enter the circulating blood,
remain in the reticulocyte stage in the
they remain in the reticulocyte stage for an average
blood stream?
of 1 day.
What is the percentage of reticulocytes in Reticulocytes represent approximately 0.5% to 1.5%
the circulating erythrocytes?
of the circulating erythrocytes.
1
Hematology PPT Flashcards Unit 2
Describe the general characteristics of cells
during erythrocyte development
Describe a mature erythrocyte
What are Reticulocytes?
What is a reticulocyte count?
What is a corrected reticulocyte count?
What is a Reticulocyte production index?
After the reticulocyte stage, the mature
erythrocyte (RBC red blood cell) is formed.
An RBC has an average diameter of 6 to 8
mm.
A supravital stain, such as new methylene
blue, precipitates the ribosomal RNA in
these cells to form a deep-blue, mesh-like
network.
- The reticulocyte count procedure (see
Chapter 26) is frequently performed in the
clinical laboratory as an indicator of the rate
of erythrocyte production.
- Usually, the count is expressed as a
percentage of total erythrocytes. The normal
range is 0.5% to 1.5% in adults. In newborn
infants, the range is 2.5% to 6.5%, but this
value falls to the adult range by the end of
the second week of life.
The corrected reticulocyte count be made
mathematically by correcting the observed
reticulocyte count to a normal packed red
blood cell volume.
- A simple percentage calculation of
reticulocytes does not account for the fact
that prematurely released reticulocytes
require from 0.5 to 1.5 days longer in the
circulating blood to mature and lose their
net-like reticulum.
- The RPI measures erythropoietic activity
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Hematology PPT Flashcards Unit 2
How do you calculate Reticulocyte production
index (RPI)?
What is polycythemia?
What is secondary, or absolute, polycythemia?
What is associated with red cell increase?
How is megaloblastic maturation associated with
anemia?
In megaloblastic maturation, what are the most
noticeable characteristics?
How can megaloblastic maturation make cells
look younger than they actually are?
How is the hemoglobin gene inherited?
What is the role of 2,3-diphosphoglycerate?
Where is 2,3-diphosphoglycerate located?
How is 2,3-diphosphoglycerate abbreviated?
when stress reticulocytes are present. The
rationale for obtaining this value is that the
life span of the circulating stress
reticulocytes is 2 days instead of the normal
1 day.
- To compensate for the increased
maturation time and consequent retention of
residual RNA of the prematurely released
reticulocytes, the corrected reticulocyte
count is divided by a correction factor
derived from the maturation timetable.
RPI = [ corrected reticulocyte count in % ]
[maturation time in days]
Polycythemia is the term used to refer to an
increased concentration of erythrocytes
(erythrocytosis) in the circulating blood that
is above normal for gender and age.
Secondary, or absolute, polycythemias
reflect an increase in erythropoietin
production and should not be confused with
polycythemia vera (see Chapter 21) or
relative polycythemias.
Increases in erythrocytes can result from
conditions that are not related to increased
erythropoietin production. These conditions
include the relative polycythemias.
A defect in maturation known as
megaloblastic maturation can be seen in
certain anemias, such as vitamin B12 or
folate deficiencies.
The most noticeable characteristic of this
type of defect is that nuclear maturation lags
behind cytoplasmic maturation. Because of
an impaired ability of the cells to synthesize
DNA, both the interphase and the phases of
mitotic division are prolonged.
The nuclear development is halted,
meanwhile the cytoplasmic development
continues. And nuclear development is
determined by the cytoplasmic
development.
Normal adult hemoglobin A is inherited in
simple mendelian fashion.
Regulate the oxygen affinity of the
hemoglobin molecule.
In the erythrocyte
2,3-DPG
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Hematology PPT Flashcards Unit 2
What is the basic manner in which 2,3-DPG
binding to reduced hemoglobin
(deoxyhemoglobin) affects oxygen affinity?
What mechanism is responsible for approximately
three fourths of the activity for removing carbon
dioxide?
In the predominant indirect erythrocyte
mechanism, carbon dioxide is catalyzed by what
enzyme?
What is carbon dioxide transformed into at the
end of the predominant indirect erythrocyte
mechanism?
What is the formula for the predominant indirect
erythrocyte mechanism?
What happens to the hydrogen ion of carbonic
acid?
What happens to the bicarbonate ion?
What is the chemical formula for this?
What enzyme is the a key regulator of the entry of
iron into the circulation.
2,3-DPG combines with the beta chains of
deoxyhemoglobin and diminishes the
molecule’s affinity for oxygen.
The predominant indirect erythrocyte
mechanism
Starting from 5’ to 3’ what is the order of globin
gene clusters for Beta Globulin and Alpha
Globulin.
For Beta Globulin Gene Cluster:
Epsilon, Gamma, Delta, Beta
During the Beginning stage of Hemoglobin
formation, what does Glycine and Succynyl CoA
form and what enzyme catalyzes the reaction.
What are porphyrias and how are they classified?
carbonic anhydrase
Carbonic acid
H2O + CO2 --------- H2CO3
It is accepted by the alkaline
deoxyhemoglobin
It diffuses back into the plasma
H2CO3 ----------- H+ + HCO3 Hepcidin.
For Alpha Globulin Gene Cluster:
Zeta2, Zeta 1, Alpha 2, Alpha 1
Succinyl-CoA and glycine are combined by
ALA synthase to form δ-aminolevulinic
acid (dALA)
Porphyrias are disorders in the synthesis of
porphyrin.
Porphyrias can be classified by:

What are disorders of Iron Metabolism?
What are the causes of Sideroblastic Anemia?
Clinical presentation (acute versus
chronic)
 Source of enzyme deficiency
Site of enzyme deficiency in the heme
biosynthetic pathway
 Genetic Defect of Iron
 Iron Overload
 Sideroblastic Anemia

congenital defect, acquired effect,
association with malignant marrow
disorders, Secondary to drugs, and
4
Hematology PPT Flashcards Unit 2
What is Type 1 Hereditary Hemochromatosis
What is Type 2 Hereditary Hemochromatosis?
toxins.
Hereditary Hemochromatosis that is
 HFE-1 Gene Related.
Hereditary Hemochromatosis that is from
Different mutations of the HJV gene.
When does Type 3 Hereditary Hemochromatosis
appear?
Type 3 Hereditary Hemochromatosis appear in
midlife.
What is Type 4 Hereditary Hemochromatosis?
Hereditary Hemochromatosis Type 4 is
related to the SLC40A1 gene that encodes
for ferroportin.
Is a highly coordinated with porphyrin
synthesis. When globin synthesis is
impaired, protoporphyrin synthesis is
correspondingly reduced. Similarly, when
porphyrin synthesis is impaired, excess
globin is not produced
Important substances in the body, one of
these is hemoglobin, the protein in red blood
cells that carries oxygen in the blood.
Globulin is a protein in plasma like albumin.
Iron is an important ingredient for the
synthesis of hemoglobin, lack of iron can
cause Iron Deficiency Anemia.
Ferritin act as a storage to store Iron in the
liver.
A family of inherited blood disorders that is
characterized by decreased production of
either alpha or beta-globin chains of the
hemoglobin molecule
Ontogeny of Hemoglobin is an Embryonic
Hemoglobins(HbsE)
Are primitive hemoglobins formed by
immature erythrocytes in the yolk sac. They
are found in the human embryo and persist
until approximately 12 weeks of
Gestation.
Is the predominant hemoglobin variety in
the fetus and the newborn. This hemoglobin
type has 2 alpha
And two gamma chains.
Is an adult hemoglobin is predominantly of
the A variety (95% to 97%)
 A subfraction of normal HbA is
HbA1.
 This subfraction can be termed
What is the disorders of globulin synthesis?
What is porphyrin?
What is globulin?
What is Iron?
What is ferritin?
What is Thalassemias?
What is Ontogeny of Hemoglobin?
What is HbsE?
What is Fetal Hemoglobin?
What is Hemoglobin A?
What is Glycosylglyated Hemoglobin (HbA1)?
5
Hematology PPT Flashcards Unit 2
List the variant forms of normal hemoglobin:
Where are abnormal hemoglobin molecules
found?
What method is used for identification of
abnormal hemoglobin?
How was hemoglobin separated on
electrophoresis?
How was hemoglobin migrated on Citrate agar
electrophoresis?
When should hemoglobin specimens undergo
electrophoresis on acid citrate agar?
Glycosylated hemoglobin and
includes the separate Hb fractions
A1a, A1b, and A1c.
 This type of hemoglobin is formed
during the maturation of the
erythrocyte. Because proteins are
vulnerable to modification after
being synthesized by the ribosomes,
this modification takes the form of
glycosylation of hemoglobin in
hyperglycemic persons.
 The concentration of glycosylated
hemoglobin accurately reflects the
patient’s blood glucose level over
the preceding weeks and has been
recently used to monitor the control
of diabetes.
The concentration of hemoglobin A1 is 3%
to 6% in normal persons and 6% to 12% in
both insulin-dependent and non–insulindependent diabetics.
– Carboxyhemoglobin
– Sulfhemoglobin
Methemoglobin
o Abnormal hemoglobin
molecules such as those seen
in sickle cell anemia result
from mutant, codominant
genes.
o A method for the preliminary
identification of abnormal
hemoglobin is
electrophoresis.
o In this method, hemoglobins
are separated on the basis of
a complex interaction
between hemoglobin, agar,
and citrate buffer ions.
o Citrate agar separates
hemoglobin fractions that
migrate together on cellulose
acetatehemoglobins S, D,
G, C, E, and O.
o All hemoglobin specimens
that show an abnormal
electrophoretic pattern in
alkaline media should
undergo electrophoresis on
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Hematology PPT Flashcards Unit 2
What is the Kleihauer-Betke procedure?
How can chromatography be used in the analysis
of hemoglobin?
What are the membrane characteristics and
metabolic activities of erythrocytes?
How is energy for metabolic process generated
for erythrocytes?
What might the overall pathway of erythrocyte
glycolysis be subdivided into?
What are the three supplementary pathways?
The shape of the erythrocyte constantly changes
when?
The cellular membrane is composed of?
The cell membrane is deformable and tolerant
against?
When does the cell shape reversibly changes?
In addition to hemoglobin, the cytoplasmic
contents of the erythrocyte include?
acid citrate agar.
It’s commonly used to determine the
amount of fetal blood that has mixed with
maternal blood following delivery.
Quantitation of hemoglobin A1 can be
accomplished by cation exchange
minicolumn chromatography. However, the
results of this technique can be affected by
several types of hemoglobin in addition to
hemoglobin A1. Cellulose acetate and citrate
agar electrophoresis should be used in
conjunction with cation exchange
chromatography to eliminate the possibility
of interference by hemoglobin variants.
Other assay methods for glycosylated
hemoglobin include high-pressure liquid
chromatography (HPLC) and colorimetric
methods.
The mature erythrocyte has no nucleus of
other organelles but is capable of existing in
the blood circulation for an average of 120
days. An erythrocyte has a limited ability to
metabolize fatty acids and amino acids and
lacks mitochondria for oxidative
metabolism.
It’s generated almost exclusively through
the breakdown of glucose and acts in these
processes are essential for the erythrocyte to
transports oxygen and to maintain the
physical characteristics required for survival
in the blood circulation.
Into the major anaerobic Embden-Meyerhof
glycolytic pathway that generates ATP and
maintains the function of hemoglobin or
into the three supplementary pathways.
The methemoglobin reductase pathway, the
Luebering-Rapoport pathway and the
phosphogluconate pathway.
It moves through the circulation and
performs extremely complex maneuvers.
A protein-lipid bilayer with associated
antigens.
Mechanical stress and various pH and salt
concentrations in vivo and in vitro.
Depending on ATP level in the cell and
intracellular calcium ion concentration.
Potassium ions in excess of the
concentration of sodium ions, glucose, the
7
Hematology PPT Flashcards Unit 2
In addition to hemoglobin, the enzymes
synthesized during early cell development have to
be sufficient to provide the energy needed for?
If metabolic pathways are blocked or inadequate,
the life span of the erythrocyte is reduced and
hemolysis results. Therefore, defects in
metabolism can occur. What are some of the
defects?
What is the most common erythrocytic enzyme
deficiency, which involves the Embden-Meyerhof
glycolytic pathway?
What are 4 metabolic activities?
Where can anexceptions to the normal
erythrocytic life span be found?
What happens to an erythrocyte as it ages?
What happends when an erythrocyte is
phagocytized and digested by macrophages of the
mononuclear phagocytic ?
What are the resulting components when
molecules are disassembled ?
The iron required for heme production is
transported to the _________from other areas in
the _____via the bloodstream by a ______called
_____
intermediate products of glycolysis, and
enzymes.
1) Maintaining hemoglobin iron in an active
ferrous (Fe 2+) state
2) Driving the cation pump needed to
maintain intracellular sodium ion (Na+) and
potassium ion (K+) concentrations despite
the presence of a concentration gradient
3) Maintaining the sulfhydryl groups of
globins, enzymes, and membranes in an
active reduced state
4) Preserving the integrity of the membrane
1) Failure to provide sufficient reduced
glutathione, which protects other elements
in the cell from oxidation
2) Insufficient energy-providing coenzymes
such as reduced nicotinamide-adenine
dinucleotide (NADH), nicotinamide-adenine
dinucleotide phosphate hydrogenase
(NADPH), and ATP
Pyruvate kinase.
1) Embden-Meyerhof pathway
2) Oxidative pathway or hexose
monophosphate shunt
3) Methemoglobin reductase pathway
4) Luebering-Rapaport pathway
In premature infants, whose erythrocytes
have a mean life span of only 35 to 50 days,
and in fetuses, in which case erythrocytes
have an average life span of 60 to 70 days.
1) The membrane becomes less flexible.
2) The concentration of cellular hemoglobin
increases.
3) Enzyme activity, particularly glycolysis,
diminishes.
system the hemoglobin molecule is
disassembled
Iron, protoporphyrin, globin
Bone marrow
Body
Transport
Protein
Transferrin
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Hematology PPT Flashcards Unit 2
What is the function of hemoglobin
In order for the heme iron to be capable of
binding O2 it must be in its ___________What is oxyhemoglobin?
What is deoxyhemoglobin?
What is carbaminohemoglobin?
Mean corpuscular volume ?
Mean corpuscular hemoglobin concentration
(mchc)
Mcv equation
Mchc equation
Haptoglobin takes the hemoglobin dimer to the
_____ and then what happens_______
Haptoglobin is made in the ____
If RBC are being broken down by the
intravascular system at 90% how does
haptoglobin response
What does corpuscular hemoglobin (MCH)
mean?
What does corpuscular hemoglobin concentration
(MCHC) mean?
To transport O2 and to a lesser extent CO2
Reduced state ferrous state, Fe2+
It is hemoglobin with oxygen bound to its
heme molecules transporting O2
Hemoglobin that is not currently
transporting O2
No O2 bound to its hemes ready to transport
Hemoglobin that is transporting carbon
dioxide CO2 instead of O2
A measure of the average red blood cell
size calculated by dividing the volume
of packed red blood cells by the total
number of red blood cells
a calculation of the average hemoglobin
concentration in each red blood cell using
hgb and hct results
mchc=hgb/hct
Hct (%) rbc count millions /mm3) x10 8589 cubic microns
Hbg(g/l) /hct(%)x100 32-36 of rbc is
hemoglobin
Reticuloendothelial system process
continues as normal
Liver
Haptoglobin levels decrease because the
liver cannot keep up with the over
breakdown
– The MCH expresses the
average weight (content) of
hemoglobin in an average
erythrocyte. It is directly
proportional to the amount of
hemoglobin and the size of
the erythrocyte.
– MCH = picograms (pg)
– The reference value of MCH
is 27 to 32 pg.
–
The MCHC expresses the
average concentration of
hemoglobin per unit volume
of erythrocytes. It is also
defined as the ratio of the
weight of hemoglobin to the
volume of erythrocytes.
– MCHC = g/dL
a. The normal value of MCHC is
9
Hematology PPT Flashcards Unit 2
What is bilirubin?
Where bilirubin is excreted in?
What color is responsible for bilirubin?
What happen when red blood cell are old (RBC’s
breakdown)?
What is the globin chains (proteins)?
What are the alpha and beta chains?
What are The heme units
Is Iron is quite toxic?
What is Iron essential for its role?
Where Iron’s toxicity is comes from?
What happen when hemoglobin is broken down?
Where the iron is stored in?
Hemoglobin in RBC’s is broken down to what?
32% to 36%.
• Hemoglobin in RBC’s is
broken down to bilirubin
• It excreted in bile and urine,
and elevated levels may
indicate certain diseases.
• The yellow color of bruises,
the straw-yellow color of
urine, the yellow color of
jaundice, and brown color of
feces.
Their cell membranes become irregular and
they become trapped in the reticular fibers
in the spleen.
• A macrophage engulfs it, and
breaks down the hemoglobin,
which is made from heme (a
porphyrrin ring with iron in
the center), and globin
chains. These three segments
of hemoglobin are detached
from each other and
liberated.
The globin chains (proteins) are broken
down into amino acids (the building blocks
of proteins), which are used for synthesis of
any other proteins wherever they are
needed.
The globins.
The porphyrin rings.
Iron is essential to nearly all cells but also is
quite toxic
It’s role in oxidation-reduction reactions
needed for metabolism.
It’s propensity to form oxygen radicals that
damage cells.
Therefore, it has to be transported in the
blood by special proteins, taken to cells that
need it, and stored in those cells by being
bound to other special proteins.
The iron (Fe+2) is released into plasma; a
protein called apoferrin binds to it (now the
apoferrin is called transferrin), and takes it
into cells that can use or store it.
Most body cells as ferritin (Fe+3) or as
hemosiderin in white blood cells
bilirubin
10
Hematology PPT Flashcards Unit 2
Bilirubin is excreted in bile and urine, and ? levels
may indicate certain diseases.
what is responsible for the yellow color of
bruises, the straw-yellow color of urine, the
yellow color of jaundice, and brown color of
feces?
When RBC’s are old, their cell membranes
become irregular and they become trapped in the
reticular fibers in the spleen. A macrophage
engulfs it, and breaks down 1, which is made
from heme (a porphyrrin ring with iron in the
center), and 2. These three segments of
hemoglobin are detached from each other and
liberated.
What type of chains are broken down into amino
acids (the building blocks of proteins), which are
used for synthesis of any other proteins wherever
they are needed?
Tor F? Iron is essential to nearly all cells but also
is quite toxic.
Iron is essential for its role in oxidation-reduction
reactions needed for what?
Its toxicity comes from its propensity to form
oxygen radicals that damage what?
When hemoglobin is broken down, the iron (Fe+2)
is released into plasma; a protein called apoferrin
binds to it (now the apoferrin is called
transferrin), and takes it into cells that can use or
store it. The iron is stored in most body cells as
what in white blood cells?
What happens to RBC’s when they are old?
What does a macrophage do?
What is the broken form of hemoglobin?
What are globulin chains?
What are amino acids?
What is essential to nearly all cells but also is
quite toxic?
What role is iron essential for metabolism?
Where does irons’ toxicity come from?
How is blood transported in the blood?
When hemoglobin is broken down, the iron (Fe+2)
is released into what?
elevated
Bilirubin
1. hemoglobin
globin chains
–
globin chains (proteins)
–
True
–
metabolism.
–
cells.
–
ferritin (Fe+3) or as hemosiderin
Cell membranes become irregular and they
become trapped in the reticular fibers in the
spleen
Engulfs and breaks down the hemoglobin
HemeProtein
Building blocks of proteins
Iron
Oxidation-reduction reactions
Its propensity to form oxygen radicals that
damage cells
By special proteins, taken to cells that need
it, and stored in those cells by being bound
to other special proteins
Plasma
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Hematology PPT Flashcards Unit 2
How does transferrin come about?
How is Iron stored in most body cells?
How is Iron stored in White Blood cells?
What is converted in the macrophage to
unconjugated bilirubin, which is released into the
blood?
Where does unconjugated bilirubin taken to be
conjugated?
What does hydrophobic mean?
What does unconjugated bilirubin have to bind to
since it is hydrophobic?
What is albumin?
What does total bilirubin consist of?
Conjugated bilirubin is also known as?
Unconjugated bilirubin is also known as?
How do you calculate unconjugated bilirubin?
Unconjugated Hyperbilirubinemia is?
What does Hyperbilirubinemia occur?
Most commonly occurs naturally in what age
range?
Where is the unconjugated bilirubin taken and
where does it enter?
Within the hepatocyte, it is conjugated(joined)
with what?
Describe the process of enterohepatic circulation
What is the process/pathway that the conjugated
bilirubin travels called?
What percentage of conjugated bilirubin is
reabsorbed?
What percentage of conjugated bilirubin goes
through the intestines?
How is urobilinogen formed?
Urobilinogen is further oxidized to which
substance that gives feces its brown color?
Which gives urine its yellow color?
By a protein called apoferrin binds to Iron.
As Ferritin
Hemosiderin
The porphyrin ring.
The liver
Not soluble in water
Albumin
A protein carrier
Conjugated and Unconjugated Bilirubin
Direct
Indirect
By subtracting direct bilirubin from total
bilirubin
A high level of unconjugated bilirubin in a
blood test.
 Result from increased production of
bilirubin because too many RBC’s are
broken down
A liver problem that causes impaired
conjugation, or impaired hepatic reuptake of
bilirubin
Newborns.
Liver, hepatocyte(liver cell)
Glucuronic acid
The conjugated bilirubin first travels to the
gallbladder as bile, then into small intestine,
back to liver, gallbladder, and put back into
intestines again
Enterohepatic circulation
95.00%
5.00%
Conjugated (direct) bilirubin is metabolized
by colon bacteria
Stercobilin
A small amount of the urobilinogen is
oxidized to uribilin and is excreted in the
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Hematology PPT Flashcards Unit 2
The high levels of uribilin turns the urine into
what color?
True or False: white stools indicate obstruction in
the bile duct
True or False: Without the brown color in the
feces, they will look black.
The conjugated bilirubin can only exit the body
by the urine when what occurs:
What does high serum levels of conjugated
bilirubin mean?
What are the causes of hyperbilirubinemia?
What causes the bile duct to be obstructed?
Obstructed bowels result from:
What is systemic illness?
Liver disease, bile duct, obstruction, obstructed
bowels, and systemic illness cause which
condition?
5% of conjugated bilirubin goes to where? And is
broken down by what?
What are the effects of conjugated and
unconjugated bilirubin?
What does bilirubinuria implies?
Why Unconjugated bilirubin is not found in
urine?
What kind of bilirubin can be found in urine?
urine.
Deep orange yellow
TRUE
FALSE
If there is a blockage of the bile duct
The liver is conjugating the bilirubin, but
the bilirubin is not being excreted in the
stools.
Liver disease esp. hepatitis, bile duct
obstruction, obstructed bowels, systemic
illness
Hemolytic diseases such as malaria, sickle
cell disease may predispose patients to
biliary obstruction through pigment
gallstones formation.
Parasite infections like tapeworms
Sepsis or cardiogenic shock
Hyperbilirubinemia
Colon, bacteria
If there is excess unconjugated bilirubin, it
will cause jaundice.
If there is excess conjugated bilirubin, it will
turn the urine dark amber.
An elevated level of conjugated serum
bilirubin implies liver disease because only
conjugated bilirubin appears in urine,
bilirubinuria can implies liver disease.
Unconjugated bilirubin is tightly bound to
albumin, not filtered by the kidney, so it is
never in the urine even with raised serum
levels of unconjugated bilirubin
If there is bilirubin in the urine (called
bilirubinuria), it is always conjugated.
Usually, their blood levels of conjugated
bilirubin are also high.
In the assessment of a patient with raised
total bilirubin, urinalysis for bilirubin and
urobilinogen may be helpful in identifying
the underlying pathology.
13
Hematology PPT Flashcards Unit 2
Describe the fetus hemoglobin
When a deoxygenated RBC from the
capillary bed in the placenta of the fetus
passes close to an oxygenated RBC in the
mother’s blood vessel, the oxygen is pulled
off the mother’s red blood cell and is pulled
into the fetus’ red blood cell.
What are the types of Hemoglobin?
There are two types of hemoglobin: fetal
hemoglobin and adult hemoglobin.
Fetal hemoglobin has a higher affinity for
oxygen (attracts and holds onto oxygen
more strongly) than does adult hemoglobin
Since fetal hemoglobin has a high affinity
for oxygen, it will not release the oxygen
into the tissues very easily, so the old RBC’s
with fetal hemoglobin need to go to the
spleen to be destroyed during the first week
of life, while new RBC’s with adult
hemoglobin are made in the bone marrow
and released into the blood stream.
How does the fetus oxygenate their own RBC’s ?
How does jaundice usually present itself in a
newborn child?
What is the treatment for a newborn with
jaundice?
What is the term for too much unconjugated
bilirubin in the bloodstream?
If hyperbilirubinemia is manifested in a newborn,
how would this affect the child if not treated in
time?
Bilirubin-induced brain dysfunction
When a person has jaundice, is it high levels of
conjugated or unconjugated bilirubin?
What type of jaundice is formed when the
bilirubin has not been conjugated yet because
there is too much of it from hemolytic anemia?
How is hepatic jaundice manifested in the body?
What type of jaundice is formed if the bilirubin
has been conjugated but bile duct is obstructed?
Pre-hepatic jaundice is caused by anything which
When the liver has reached its maximum
capacity for conjugating the bilirubin, the
excess unconjugated bilirubin leaks into the
bloodstream, causing jaundice, which is
common in newborns and not usually
harmful.
Treatment is exposure to ultraviolet light, to
assist the breakdown process of bilirubin.
Hyperbilirubinemia
Hyperbilirubinemia in a newborn can lead
to accumulation of bilirubin in the brain,
causing irreversible damage, manifesting as
seizures or abnormal reflexes and eye
movements.
Kernicterus
It depends on what is causing the jaundice.
Pre-hepatic jaundice
The bilirubin has not been conjugated yet
because of liver damage such as alcoholism
Post-hepatic jaundice
Malaria, sickle cell anemia, Hereditary
14
Hematology PPT Flashcards Unit 2
causes an increased rate of hemolysis; what are
some examples that would lead to pre-hepatic
jaundice.
What type of jaundice could result from acute
hepatitis, hepatotoxicity or alcoholic liver
disease?
True or False
In alcoholics, their unconjugated bilirubin levels
are high in the serum because their hepatocytes
are not damaged.
What causes the elevation of the conjugated
bilirubin in alcoholics?
When ascites occurs, the abdominal fluid puts
pressure on bile duct, conjugated bilirubin was not
reabsorbed into the enterohepatic circulation, what
happens to the level of the conjugated bilirubin?
Treatment for ___________ is to drain the excess
fluid out of the abdominal cavity and have the
patient take a diuretic.
True or False
When blood leaves a ruptured blood vessel, the red
blood cell dies, and the hemoglobin of the cell is
released into the intracellular
What causes the purple color of 2-day old bruises?
White blood cells called macrophages engulf
(phagocytose) the hemoglobin to degrade it, what
is being produce from the iron and biliverdin from
the porphyrin ring?
What do you call the pigment responsible for the
greenish color of 5-day old bruises?
Biliverdin breaks down into what, causing the
bruise to turn yellow in 7-10 days, and then
brown.
The heme portion (porphyrin ring) of hemoglobin
breaks down into biliverdin (which is green),
which breaks down into unconjugated bilirubin.
What is the color of the unconjugated bilirubin?
When a bruise is brand new, it appears reddish
what causes this color?
At 1-2 days old, a bruise will take on a bluish or
purple color. This is caused by what?
A bruise will turn a greenish color as the
hemoglobin breaks down to biliverdin, at how
many days?
Spherocytosis, Hemolytic Disease of the
Newborn (HDN), G6DH deficiency.
Hepatic jaundice
False (hepatocytes ARE DAMAGED)
Lack of albumin, ascites occurs, and the
abdominal fluid puts pressure on bile duct,
so the conjugated bilirubin is not reabsorbed
into the enterohepatic circulation.
Increases
Ascites
False (Extracellular space)
Hemosiderin
Hemosiderin
Biliverdin
Bilirubin
Yellow
Due to the color of the blood that leaked
from the capillaries under the skin.
The swelling at the site of the bruise will
cause oxygen to be cut off, and hemoglobin
will turn blue.
6 days
15
Hematology PPT Flashcards Unit 2
An 8-9 days old bruise, the ______will break
down to unconjugated bilirubin, which is yellow.
Biliverdin
In a 10-14 days old bruise, what is being oxidized
and causes the bruise to turn brown.
The appearance of a bruise changes over time and
you can tell how old a bruise is by its ____.
My neighbor slipped on a wet floor and it caused
her a big bruise on her buttocks. She is concern
about the color and wondering when (how many
weeks?) will it disappear and turn back to its
normal color?
How old are these bruises? (please see table for the
answers)
Bilirubin
What is the morphology of a normal erythrocyte?
On microscopic exam, erythrocyte color can be
best seen using which stains?
Abnormal erythrocytes can be classified with the
following five variations:
A normal erythrocyte varies in diameter from ___
to ___ with an average of ___.
Erythrocytes from 6.2nm to 8.2nm are considered
___.
Erythrocytes with diameter larger than 8.2 are ___.
Erythrocytes with a diameter smaller than 6.8 are
___.
The term for increased variation in erythrocyte size
is ___.
What kind of cells are characteristic of Heinz
body-mediated hemolysis?
What are schistocytes?
Biconcave disc without a nucleus.
Wright or similar Romanowsky-type stain.
Color
The skin should look normal 2-3 weeks after
an injury.
Size, shape, color, inclusions and
distribution on a peripheral smear
6.8nm to 7.5nm
7.2nm
Normocytic
Macrocytic
Microcytic
Anisocytosis
Blister cells
Irregular, fragmented erythrocytes
16
Hematology PPT Flashcards Unit 2
Kinds of variations in erythrocytes shape
polychromatophilia or polychromasia is:
What does the alteration in color that occurs with
polychromasia in erythrocytes reflect?
reticulocytes are slightly immature RBC's that lack
the full amount of hemoglobin, and the blue
colored objects, seen within the RBC’s, when
stained are?
what stain is used to determine a reticulocytes
count?
Babesia and malaria are examples of what?
The following are examples of?
Basophilic stippling (both fine and coarse forms)
Cabot rings
Heinz bodies
Howell-Jolly bodies
Pappenheimer bodies
Siderotic granules
The "stippling" in Basophilic stippling represents?
Clinically, basophilic stippling is associated
with...
The two types of basophilic stippling are?
Which type of basophilic stippling appears as
tiny, round, solid-staining, dark-blue granules,
usually evenly distributed throughout the cell and
often require careful examination to detect them?
Which type of basophilic stippling is sometimes
referred to as punctate stippling, has larger
granules and is considered to be more serious in
terms of pathological significance?
What is the typical size of Heinz bodies?
What stains are used to view Heinz bodies?
What are Heinz Bodies?
What are Heinz bodies clinically associated with?
-Ovalocyte (elliptocyte)
-Pyknocyte (blister)
-Schistocytes and increased reticulocytes in
a patient with thrombotic thrombocytopenic
purpura.
-Drepanocyte (sickle)
-Hereditary spherocytosis
-Stomatocyte
When non-nucleated erythrocytes have a
faint blue color when stained with Wright
stain.
cell immaturity
diffusely distributed residual RNA in the
cytoplasm.
The Supravital Stain, New methylene blue
Red blood cell parasitic inclusions.
Nonparasitic red blood cell inclusions
granules composed of ribosomes and RNA
that are precipitated during the process of
staining of a blood smear.
disturbed erythropoiesis (defective or
accelerated heme synthesis), lead poisoning,
and severe anemias.
Fine and coarse
Fine basophilic stippling
Coarse basophilic stippling
0.2-2.0 mm in size
Crystal violet or brilliant cresyl blue
Represent precipitated denatured
hemoglobin
1) Congenital hemolytic anemia
17
Hematology PPT Flashcards Unit 2
2) G6PD deficiency
3) Hemolytic anemias secondary to
drugs such as phenacetin
4) Some hemoglobinopathies
What do Howell-Jolly (H-J) bodies look like?
What are Howell-Jolly bodies?
How are H-J bodies believed to develop?
What are the presence of H-J bodies clinically
associated with?
The following Inclusions are seen in what type of
cell?
-Pappenheimer bodies (siderotic granules)
-May be observed in wright-stained smears as
purple dots.
-Are infrequently seen in peripheral blood smears.
-Are aggregates of mitochondria, ribosomes, and
iron particles
-Are clinically associated with iron-loading
anemias hyposplenism, and hemolytic anemias.
_____ bodies and sideritic granules are probably
identical structures.
These type of granules are dark-staining particles
of iron in the erythrocyte that are visible with a
special iron stain-Prussian blue. They appear as
blue dots and represent ferric (Fe3+) ions.
This formation abnormality of erythrocytes is
associated with the presence of cryoglobulins.
True agglutination is caused by the presence of
antibodies reacting with ____ on the erythrocyte.

Round, solid-staining, dark blue to
purple inclusions (1 or 2), usually 12mm in size
 Nuclear remnants predominantly
composed of DNA and not seen in
normal erythrocytes
 They develop in periods of
accelerated or abnormal
erythropoiesis, because the spleen
can’t keep up with pitting these
remnants from the cell.
1) Hemolytic anemias
2) Pernicious anemia, particularly
postsplenectomy
 Physiological atrophy of the spleen
Erythrocytes
Pappenheimer
Siderotic granules
Rouleaux formation
Antigens
18
Hematology PPT Flashcards Unit 2
Rouleaux
What is the name of the erythrocyte alteration
depicted above?
Malaria disease cycle
What disease cycle is depicted above?
What is the 1st stage in the Malaria disease
cycle?
What is the name of the 2nd stage in the
Malaria disease cycle?
What is the name of the 3rd stage in the
Malaria disease cycle?
What happens in the 4th stage of the Malaria
disease cycle?
What happens in the 5th stage of the Malaria
disease cycle?
What happens in stage 5a of the Malaria
disease cycle?
What happens in the 6th stage of the Malaria
disease cycle?
What happens in the 7th stage of the Malaria
disease cycle?
What happens in the 8th stage of the Malaria
disease cycle?
What happens in the 9th stage of the Malaria
disease cycle?
Sporozoite invades the red blood cell
Ring stage
Ameboid stage
Asexual division
Cell rupture with release of spore
Reinfection of RBC by some spores
Development of other spores into sexual
forms
Development into egg and sperm cells after
mosquito sucks them in
Fertilized cell develops into a cyst
Ruptured cyst releases sporozoites
19
Hematology PPT Flashcards Unit 2
Schizonts, trophozoites, and unlysed
leukocytes
What types of parasitic inclusions are depicted
above?
Microgametocytes and several ring forms
What types of parasitic inclusions are depicted
above?
Ring forms from P. Falciparum
What type of parasitic inclusion is depicted
above?
A Gametocyte
What type of parasitic inclusion is depicted
above?
20
Hematology PPT Flashcards Unit 2
Identify:
Parasitic inclusions in erythrocyte (Malaria)
Identify:
Parasitic inclusion in erythrocyte
(Leishmania sp)
Identify:
Parasitic inclusion in erythrocyte
(Babesiosis)
What is general term for mature erythrocytes that
have a shape other than the normal round,
biconcave appearance on a stained blood smear,
or variations
What are the kinds of variations in erythrocyte
shape?
What does a normal erythrocyte looks?
Poikilocytosis
What is normochromic?
What is the general term for a variation in the
normal coloration?
Teardrop
Target
A normal erythrocyte has a moderately
pinkish-red appearance with a lightercolored center when stained with a
conventional blood stain.
The color reflects the amount of hemoglobin
present in the cell. The lighter color in the
middle, thinner portion of the cell does not
normally exceed one third of the cell’s
diameter and is referred to as the central
pallor.
Anisochromia
21
Hematology PPT Flashcards Unit 2
What does it determine if an alteration in the
color of an erythrocyte occurs?
What term is used if a nonnucleated erythrocyte
has a faintly blue-orange color?
If the hemoglobin concentration of the RBCs or
hematocrit is below the limit of the 95% interval
for the patients age, gender, and geographical
location, what is considered to be present?
What 3 major categories does anemia fall under?
True or False?
Anemia may be a sign of an underlying disorder
The dilution of anemia with normal or increased
total red cell mass is seen in?
True or False?
Anemias only have one pathogenic mechamism
and go through only one morphological state.
Cell immaturity
Polychromatophilia
Anemia
Blood loss, impaired red cell production,
and accelerated red cell destruction
(hemolysis in excess of the ability of the
marrow to replace these losses)
True
Pregnancy, macroglobulinemia, and
splenomegaly
False. Some anemias have more than one
pathogenic mechanism and go through more
than one morphological state such as blood
loss anemia
What occurs in accelerated red cell destruction?
Hemolysis in excess of the ability of the
marrow to replace these losses
What are clinical signs and symptoms of anemia a diminished delivery of oxygen to the tissues.
result of?
What are the signs and symptoms of anemia
lowered hemoglobin concentration
related to?
What else do the signs reflect?
the rate of reduction of hemoglobin and
blood volume
If anemia develops slowly in a patient who is not hemoglobin concentration of as low as 6
otherwise severely ill how low can concentration g/deciliters may develop without producing
of hemoglobin get?
any discomfort or physical signs if the
patient is sedentary
What are the usual complaints of an anemic
are easy fatigability and dyspnea on
patient?
exertion
What are other general manifestations of anemia? vertigo, faintness, headache, and heart
palpitations
What are the most common physical expressions
are pallor, low blood pressure, a slight fever,
of anemia?
and some edema
How is anemia classified?
morphology, physiology, or probable
etiology
How did Wintrobe categorize anemias?
by the size of the erythrocytes.
How else can anemia be classified by red cell
as macrocytic, normocytic, or microcytic.
morphology?
What is the limitation of red cell morphology
it tells nothing about the etiology or reason
classification of anemia?
for the anemia.
What is the limitation of classifying anemia by
within each classification the various
etiology?
subdivisions are not completely inclusive
22
Hematology PPT Flashcards Unit 2
What is the advantage of etiology?
What are three major categories in this system?
What are the most frequent forms of anemia?
What does laboratory investigation of anemias
involve?
The results of these analyses provide the
foundation for what two things?
What is physiologically defined as a condition in
which the circulating blood lacks the ability to
adequately oxygenate body tissues?
How many major laboratory manifestations of
anemia are?
describes the basic mechanism or probable
mechanism responsible for the anemia
are accelerated erythrocyte destruction,
blood loss, and impaired RBC production.
result from either blood loss or iron
deficiency conditions
quantitative and semiquantitative
measurements of erythrocytes and
supplementary testing of blood and body
fluids.
both the diagnosis and treatment of anemia
Anemia
These are:
A decreased hemoglobin concentration
A reduced packed cell volume
(microhematocrit) level
A decreased erythrocyte concentration
What are assessments to the direct measurement
of hemoglobin, packed cell volume
(microhematocrit), and erythrocyte count, a
variety of other measurements or calculations can
yield additional information?
These assessments include the following:
Red blood cell indices
The red cell histogram
Red cell distribution width (RDW) or red
cell morphology index (RCMI)
Where is the best area on a blood smear for the
examination of red cell morphology?
Under 10x (low-power), is it possible to evaluate
the relative number of white blood cells?
That is where the red cells are barely
touching each other but not overlapping
Yes, approximately one WBC for every
1000 and rbc's, and one platelet that for
every 10 rbc's.
Erythrocyte are reported using the following
descriptive terms, such as moderate or
marked, or grades on a numerical scale,
such as 1+, 2+, 3+, or 4+.
The characteristics of such a grading scale
may vary from one laboratory to another
A bone marrow examination may be
performed and may reveal an abnormal
ratio of leukocytes to erythrocytes, the
myeloid-erythroid (M:E) ratio.
Fetal hemoglobin (Hb F) concentration
Malarial smears
Platelet count
Reticulocyte count
Sickle cell testing
Glucose-6-phosphate dehydrogenase (G6PD) assay
23
How is semiquantitive grading of erythrocyte
morphology?
What are assays performed in the hematology
laboratory and others may be performed in
another section of the clinical laboratory?
Hematology PPT Flashcards Unit 2
Hemoglobin electrophoresis
What are additional procedures, usually
performed in other sections of the clinical
laboratory?
These procedures include the following:
Antibody screening and identification tests
Direct antiglobulin (AHG) test
Measurements of bilirubin levels
Folic acid assay
Measurement of haptoglobin level
Lactic dehydrogenase (LDH) determination
Serum iron and total iron-binding capacity
(TIBC)
Vitamin B12 assay
Occult blood testing
Urobilinogen screening
What are the etiology of the acute blood loss
anemia?
•
What are the physiology of the acute blood loss
anemia?
What are the physiology of the acute blood loss
anemia?
Etiology
•
The acute loss of blood is
usually associated with
traumatic conditions such as an
accident or severe injury.
Occasionally, acute blood loss may occur
during or after surgery.
•
Physiology
•
An acute blood loss does not
produce an immediate anemia.
•
A severe hemorrhage or rapid
blood loss amounting to more
than 20% of the circulating
blood volume reduces an
individual’s total blood volume
and produces a condition of
shock and related
cardiovascular problems.
1. Even if enough hemoglobin remains in
the circulation, and oxygen and
impairment can exist because of
circulatory failure.
•
Physiology
•
However, severe acute bleeding
can be fatal as a result of the
collapse of the circulatory
system; immediate expansion of
the blood volume is required.
•
In acute blood loss, the body
itself adjusts to the situation by
expanding the circulatory
volume, which produces the
24
Hematology PPT Flashcards Unit 2
What are the laboratory findings of the Acute
blood loss anemia?
What are the laboratory findings of the acute
blood loss anemia?
What are the laboratory findings of the acute
blood loss anemia?
After acute blood loss how long does it take for
the total white blood cell count and the red blood
subsequent anemia.
1. Fluid from extra vascular spaces enters
the blood circulation and has a diluting
effect on the remaining cells.
•
Laboratory findings
•
Hematological findings are very
different in the patient who has
experienced an acute bleeding episode
within the past 24 to 48 hours
compared with a patient who has
suffered from chronic bleeding for
several months.
•
Laboratory findings
•
The earliest hematological
change in acute blood loss is a
transient fall in the platelet
count, which may rise to
elevated levels within 1 hour
(inflammatory reaction).
•
The next change is the
development of neutrophilic
leukocytosis (from 10 to 35 x
109/L) with a shift to the left.
1. The hemoglobin and hematocrit do not
fall immediately but fall as tissue fluids
move into the blood circulation. It can
be 48 or 72 hours after the hemorrhage
until the full extent of the red cell loss
is apparent.
•
Laboratory findings
•
The earliest hematological
change in acute blood loss is a
transient fall in the platelet
count, which may rise to
elevated levels within 1 hour
(inflammatory reaction).
•
The next change is the
development of neutrophilic
leukocytosis (from 10 to 35 x
109/L) with a shift to the left.
 The hemoglobin and hematocrit do not
fall immediately but fall as tissue fluids
move into the blood circulation. It can
be 48 or 72 hours after the hemorrhage
until the full extent of the red cell loss
is apparent.
It takes about 2 to 4 days after the blood loss
for the total white blood cell count to return
25
Hematology PPT Flashcards Unit 2
cell profile to return to normal?
What disorders are associated with chronic blood
loss?
How long does the blood loss occur in chronic
anemias?
How does chronic blood loss influence the blood
volume?
What are the laboratory findings in small amounts
of blood loss during and extended period?
What is aplastic anemia?
What are the other anemias in the same category?
What is the cause of aplastic anemia?
What are aplastic anemias considered secondary
to?
When is anemia iatrogenic?
What causes injury to proliferating and quiescent
hematopoietic cells?
Drug related and chemically realted aplastic
anemia account for what percent of cases?
What has been well documented as a cause of
aplastic anemia?
What are some examples of iatrogenic agents?
to normal.
The return of the red cell profile to previous
values takes longer.
Chronic blood loss is frequently associated
with disorders such as the following:
Gastrointestinal (GI) tract
Heavy menstruation in women
Urinary tract abnormalities
In chronic anemias, blood loss of small
amounts occurs over an extended period,
usually months.
The chronic and continual loss of small
volumes of blood does not disrupt the blood
volume.
If blood is lost in small amounts over an
extended period
Both the clinical and hematological features
seen in acute bleeding are absent.
Regeneration of red blood cells occurs at a
slower rate.
The reticulocyte count may be normal or
only slightly increased.
Aplastic anemia is one of a group of
disorders, known as hypoproliferative
disorders, that are characterized by reduced
growth or production of blood cells.
Other anemias in this category include the
following:
Deficiencies of erythropoietin
Iron
Folic acid and vitamin B12
Aplastic anemia is an unusual disease of
bone marrow failure.
Etiologic agents that are drug related
(iatrogenic) and chemically related.
When the transient marrow failure follow
cytotoxic chemotherapy or radiation
therapy.
Chemical or physical agents, which lead to
DNA damage and apoptosis.
20%
Ionizing radiation.
Benzene/benzene derivatives,
Trinitrotoluene, insecticides, weed killers,
inorganic arsenic, antibiotics, etc.
26
Hematology PPT Flashcards Unit 2
What is a feature of patients with acquired
aplastic anemia?
What inhibits the maturation and amplification of
bone marrow stem and blast cells?
In which cases are chemically aplastic anemia
reversible?
What are viral infections secondary to?
What is the mechanism associated with the
induction of aplastic anemia?
Rarely is there exposure to any substance
that is toxic to the bone marrow.
Metabolization in the liver of new benzene
to a series of structures.
depends on the extent of damage
Do INF-alpha and TNF suppress the proliferation
of early and late hematopoietic progenitor cells
and stem cells?
What helps to increase the rate of suppression
associated with INF-alpha and TNF?
Yes
bone marrow aplasia
Includes the possibility of drug exposure
during treatment, direct stem cell damage by
the virus, depressed Maddow policies by the
viral genome, and virus-induced
autoimmune damage.
Do patients with aplastic anemia have a increased Blood and Marrow from patients also
number of activated cytotoxic lymphotcytes? Will contained increased numbers of activated
therapy with anti-thymus site globulin (ATG)
cytotoxic lymphocytes, and the activity and
therapy?
numbers of these cells decreased with
successful anti-thymus site globulin (ATG)
therapy.
This suppression is greater when these
factors are secreted into the marrow
microenvironment then when they are added
to cultured cells.
Is there any information that describes the events
that precede the destruction of hematopoietic
cells?
The immunological events that precede the
destruction of hematopoietic cells are not as
clear as the mechanism of suppression of
proliferation.
Do we know what leads to the destruction of
Both the dish regulatory events that lead to
hematopoietic stem cells?
the loss of tolerance and to autoimmune
destruction of hematopoietic cells and the
initial antigen exposure that triggers
immune system activation are unknown.
Do laboratory studies of patients lymphocytes and Yes
their products support the concept of
pathophysiological roles for lymphocytes and
lymphokines in the destruction of hematopoietic
cells?
Is alpha-INF a specific marker for aplastic
Alpha-INF suppression is prevalent in
anemia?
acquired aplastic anemia and may be a
specific marker of this disease.
What may be an important mediating factor for
aplastic anemia?
Local production of this inhibitory
lymphokine in the target organ, the bone
marrow, may be important in mediating
27
Hematology PPT Flashcards Unit 2
aplastic anemia.
Would measurement of lymphokines be able to
help distinguish between aplastic anemia and
other forms of bone marrow failure?
Yes, measurement of this lymphokines
message may be useful in distinguishing
acquired aplastic anemia from other forms
of bone marrow failure.
What are characteristics of acquired aplastic
anemia?
Acquired aplastic anemia is characterized by
total bone marrow failure with a reduction
in circulating levels of red blood cells, white
blood cells, and platelets.
No
The clinical course may be acute and
fulminating, with profound pancytopenia
and a rapid progression to death, or the
disorder may have an insidious onset and a
chronic course.
Is acquired aplastic anemia a common disease?
Is acquired aplastic anemia acute or chronic?
What are some signs and symptoms of acquired
aplastic anemia?
The signs and symptoms depend on the
degree of the deficiencies and include
bleeding from thrombocytopenia, infection
from neutropenia, and signs and symptoms
of anemia. Splenomegaly and
lymphadenopathy are absent.
Recent studies have shown that long-term
survivors of acquired aplastic anemia may be at
high risk for what complications?
At what point after the disease can survivors of
acquired aplastic anemia experience
complications?
What percentage of patients does Peroxisomal
nocturnal hemoglobinuria (P and H) occur in?
At what cumulative incidence rate does mild load
dysplasia (MDS) and acute myelogenous
leukemia (AML) occur in ten years after
treatment of in patients?
Solid tumors increase after what incidence?
Subsequent malignant diseases or late clonal
hematologic diseases.
What is aplastic anemia caused by?
If all the cell lines are affected, what is the
disorder referred to as?
If only one cell line is involved, what cells?
When is a diagnosis of sever aplastic anemia
made?
Any point up to even years after successful
immunosuppressive therapy.
10%
15%
Immunosuppression and after bone marrow
transplantation.
Damage or destruction of the hematopoietic
tissue of the bone marrow that results in
deficient production of blood cells.
Pancytopenia
Erythrocytes
When at least two of the three peripheral
blood values fall below critical levels.
28
Hematology PPT Flashcards Unit 2
In aplastic anemia, the marrow is either
significantly or moderately hypo cellular, with
what percentage of residual hematopoietic cells?
In this anemia, concentration of hemoglobin in
the red blood cells is within the standard range.
However, there are insufficient numbers of red
blood cells. What is the term for this?
What is a red cell distribution whit (RDW) like in
non-transfused patients?
In aplastic anemia, leukopenia with an increase or
decrease in granulocytes is noticeable?
Is thrombocytopenia typically present in patients
with aplastic anemia?
What happens to serum iron levels in patients
with aplastic anemia?
What is increased serum plasma a valuable sign
of in patients with aplastic anemia?
What does erythorid hypoplasia reflect in patients
with aplastic anemia?
Is the erythrocyte use of iron increased or
decreased due to the increased serum iron level in
patients with aplastic anemia?
What happens to effective and total erythropoiesis
in patients with aplastic anemia?
The bone marrow reveals very few early erythroid
and myeloid cells at what stage of differentiation?
How common are mega cario sites in the bone
marrow at any stage of differentiation?
What happens to primitive progenitor and stem
cells?
Primitive progenitor and stem cells constitute
approximately what percent of marrow cells?
If acute exposure to radiation is the inciting agent,
the production of new red blood cells
(reticulocyte count) rises or falls?
Why do the red blood cells decline slowly if acute
exposure to radiation is the inciting agent?
When does a decrease in lymphocytes occur?
What is this decrease in lymphocytes responsible
for?
How long does it take for granulocytes to begin
decreasing?
What type of cells are often last to return to
normal in the recovery phase?
Aplastic anemia responds to what treatment?
What sort of damage to the body can result from
Less than 30%
Normochromatic
Normal
Decrease
Yes
It is increased
Erythorid hypoplasia
The decreased plasma iron turnover
Decreased
It is decreased
Any
Scanty if present at all
They cannot be identified by their parents
1%
Falls
Because of their long survival
After the first day
Early leukopenia
Five days
Platelets
Immunosuppressive therapy, or stem cell
transplantation
Organ destruction, the capacity for tissue
29
Hematology PPT Flashcards Unit 2
the treatment for aplastic anemia?
What factors determine treatment strategy for a
patient?
If a suitable donor is available, patients younger
than what age are indicated for allergenic bone
marrow transplantation?
What is the recommended treatment for younger
patients who have an identical twin donor or an
HLA-matched donor?
What are the two year survival rates for patients
who receive the transplant procedure?
What is the death rate?
What is the treatment of choice for Aplastic
Anemia in patients without donors and older
patients?
What can be combined with immunosuppression
when treating Aplastic Anemia?
What are inherited bone marrow failure
syndromes (IBMFS) that initially exhibit aplastic
anemia?
regeneration, and perhaps most importantly,
a drug regimen that can control a
misdirected and extraordinarily potent
immune response.
Age of the patient, and the availability of an
identical familial donor.
40 years of age
Bone marrow transplantation
70%
10%
Immunosuppression.
Anti-lymphocyte globulin (ALG),
cyclosporine-A, splenectomy and
lymphocytophoresis have been developed.
Fanconi anemia, Congenital
amegokaryocytic thrombocytopenia, and
Diamond-Blackfan anemia
What mutations in telomerase genes can lead to
aplastic anemia?
Heterozygotes mutations in TERC,
telomerase RNA component, the gene for
the RNA component of telomerase, have
been found to cause short to low mirrors in
congenital aplastic anemia.
What are telomeres enzymes in humans?
In humans, telomerase are the nucleic acid
sequence TTAGGG that is found on the
ends of our chromosomes. That sequesnce is
repeated and forms an extra thread attached
onto the ends of our DNA.
Why do the telomeres shorten every cell division?
Because Telomeres cannot be fully
duplicated during cell division
To counter telomere shortening, stem cells
and lymphocytes express the enzyme
telomerase.
Telomeres are long at birth but rapidly he
rode in the first two decades of life,
continuing to shorten with age at a slower
rate thereafter.
How is the shortening of telomeres prevented?
How does the rate of telomere shortening look
like in peripheral blood leukocytes as it ages?
30
Hematology PPT Flashcards Unit 2
What causes defects in telomere repair and
protection?
Mutations in genes that function to repair
telomerase in hematopoietic tissue results in
defects in telomere repair and protection
What are techniques that measure telomere
length?
Southern Blot, PCR, and Flow-FISH
What does excessive telomere shortening lead to?
Excessive telomere loss permeates the
pathogenesis of bone marrow failure and
malignancy.
• Peripheral cytopenias range from
absent to severe.
• Unexplained red cell macrocytosis,
especially if a family history of
marrow failure exists.
• In many cases, red cell macrocytosis
is the only hematologic abnormality.
• Macrocytosis may be masked, if a
concurrent iron deficiency or
thalassemia trait is present.
• Elevated levels of hemoglobin F are
common.
• Cells in the bone marrow may
exhibit dysplastic changes, for
example, abnormal nuclei,pseudoPelger Huet anomalies, mild mega
low blasted features with nuclear:
cytoplasmic dis-synchrony or
multinucleated erythroid precursors.
• A minority of patients with aplastic
anemia have heterozygous mutations
in genes encoding for telomerase.
These patients have an increased risk
of developing cancer, particularly
AML.
• Hypo proliferation of the erythroid
elements, without corresponding
decreases in other cell lines, is
characteristic of pure red cell
aplasia.
This condition exists in three forms but a
number of variant and intermediate forms
have been recognized.
• 1) congenital – diamond-black fan
syndrome
• 2) acquired chronic – idiopathic,
associated with thymoma and
lymphoma
What is Bone Marrow Failure Syndromes?
What is examples of Red Cell Aplasia?
31
Hematology PPT Flashcards Unit 2

What is AML?
What is Aplastic Anemia?

•
What is Pure red Cell Aplasia?

•
•
•
•
•
•
•
•
•
•
•
•
3) acute (transient) – parvovirus,
other infections, drugs, riboflavin
deficiency
Acute Myelogenous Leukemias
Aplastic anemia is one of a group of
disorders, known as
hypoproliferative disorders that are
characterized by reduced growth or
production of blood cells.
This is a disorder primarily
involving disturbed every throw
polices. New immune suppression of
erythropoiesis is believed to play a
role in this form of red cell aplasia.
An immune system etiology is
supported by the fact that some
patients respond to steroid treatment.
Patients with pure red cell aplasia
have antibodies against erythroid
precursor cells and lymphocytes
capable of inhibiting erythropoiesis.
Erythroid precursors are absent from
the bone marrow, and evidence of
hemolysis or hemorrhage is not
present in red cell aplasia.
The level of serum erythropoiesis
and is usually increased.
And a plastic crisis can develop in
some patients with hemolytic anemia
and can't commit tent infection.
Other causes of acquired red cell
aplasia include malnutrition and
neoplasia.
Thymoma (tumor of the thymus
gland) is a frequent finding.
Acquired pure red cell aplasia
characterized by selective failure of
red blood cell production rarely
occurs in middle-aged adults.
Reticulocytopenias and a cellular
marrow devoid of all but the most
primitive erythroid precursors are
characteristic.
Leukocyte and platelet production
are normal.
Approximately half of reported cases
have been associated with thymoma.
32
Hematology PPT Flashcards Unit 2
What is Etiology?
What are the clinical signs and symptoms of
Fanconi anemia?
What percentage of patients with congenital
malformations are diagnosed before the onset of
hematologic manifestations?
Progressive pancytopenia is usually apparent by
what age?
What do patients with Fanconi anemia have a
predisposition to?
What is the best way to diagnose Fanconi
anemia?
What is the traditional therapy for Fanconi
anemia?
Only 10% of patients with thymoma
have anemia. New remission of
anemia occurs in 25% of cases after
surgical removal of the thymoma
• Has been associated with other
conditions, such as drugs, collagen
vascular disorders, and
lymphoproliferative disorders.
• Most of these anemias appear to be
part of a spectrum of autoimmune
cytopenias in which the target cells
are either erythroid stem cells or
normal blasts.
• Antibodies that react with these cells
have been identified in some
patients.
– Corticosteroids and
immunosuppressive drugs have been
used as therapy, but less than 50% of
patients achieve satisfactory
remission.
– The cause, set of causes, or manner
of causation of a disease or
condition.
Clinical signs commonly include low birth
weight, skin hyperpigmentation (café au lait
spots), and short stature. Other
manifestations can include skeletal disorders
(aplasia or hypoplasia of the thumb), renal
malformations, microcephaly,
hypogonadism, mental retardation, and
strabismus.
30%
Five years of age.
Neo-plasma.
With the demonstration of increased
chromosomal breakage following exposure
to clastogenes, distinguishing Fanconi
anemia from most of the other chromosomal
breakage syndromes.
Bone marrow transplantation to ward off
hemorrhage and infection as well as
administration of steroids and androgens.
Bone marrow transplantation has been the
33
Hematology PPT Flashcards Unit 2
What are some other treatment alternatives for
Fanconi anemia?
What is a subset of Fanconi anemia?
What does the age of diagnosis vary from for
Fanconi anemia?
What symptoms do few children present with?
What do patients develop as the disease
progresses?
What might some cases of Fanconi anemia
present?
What is hepatitis-associated aplastic anemia?
What type of hepatitis is present for hepatitisassociated aplastic anemia?
How rare is hepatitis-associated aplastic anemia?
Where is aplastic anemia most common?
treatment of choice for patients with an
HLA-identical unaffected sibling however
transplantation from other donors has
produced poor results.
Cryopreserved umbilical cord blood transplantation
from a sibling shown by prenatal testing to be
unaffected by the disorder or using recombinant
granulocyte colony-stimulating factor (CSF).
New this treatment has been successful in reducing
neutropenia but is ineffective in stimulating
erythrocyte or thrombocyte cell lines.
Familial aplastic anemia with a low incidence of
congenital abnormalities.
Younger than a year old to 77 years old.
Bleeding manifestations secondary to
thrombocytopenia.
Pancytopenia and hypo cellular bone
marrow however patients may have
pancytopenia and hypo cellular marrow
without major developmental anomalies.
There may be skin hyperpigmentation or
stunted growth.
- Hepatitis-associated aplastic anemia is a
variant of aplastic anemia in which aplastic
anemia follows an acute attack of hepatitis.
- Severe pancytopenia can occasionally
occur two months after an episode of
apparent viral hepatitis.
- The stereo typical syndrome of post
hepatitis aplasia would seem to offer the
opportunity to identify a specific infectious
cause of aplastic anemia.
• In most patients, the hepatitis is nonA, non-B, non-Sea, and non-Jeep.
• The hepatitis does not appear to be
caused by any of the known hepatitis
viruses.
Several features of the syndrome suggest
that it is mediated by immuno pathologic
mechanisms.
 Although aplastic anemia is a rare
sequela of hepatitis, there is a
striking relationship between
fulminant seronegative hepatitis and
aplastic anemia.
• Epidemiological studies suggests the
involvement of an enteric microbial
34
Hematology PPT Flashcards Unit 2
How lethal is hepatitis-associated aplastic
anemia?
What happens when HLA-matched donor is not
available for bone marrow?
Impaired erythrocyte production can be caused by
a variety of factors:
What is the pathophysiology of aplastic anemia?
What is the relationship between hematopoietic
failure and aplastic anemia?
agent in the causation of aplastic
anemia.
 Aplastic anemia not only is more
common in the far east (10%
compared to 5% in the West), where
hepatitis viruses are prevalent, but
also is associated with poverty, rice
farming, and past exposure to
hepatitis A.
 Hepatitis-associated aplastic anemia
is often fatal if untreated.
 If a human leukocyte antigen
(HLA)-matched related donor is not
available for bone marrow
transplantation, immunosuppressive
treatment is given.
- Proinflammatory cytokines tumor necrosis
factor-alpha (TNF-α) and interferon-gamma
(IFN-γ) may play a role
 - Heterozygous mutations in genes
including TERC and TERT, the
genes for the RNA component of
telomerase, may be a risk factor for
marrow failure.
- The pathophysiology of aplastic anemia is
immune mediated in most cases, with
activated type 1 cytotoxic T cells
implicated.
- The molecular basis of the apparent
immune response and deficiencies in
hematopoietic cells is now being defined
genetically; examples are telomere repaired
gene mutations in the target cells and disregulated T cell activation pathways.
- Cellular immune suppression may occur
transiently with certain viral infections such
as parvovirus or as a result of drug action.
- Pure red cell aplasia is often associated
with thymomas.
- Hematopoietic failure may occur at any
level in the differentiation of bone marrow
precursor cells. New line there may be
insufficient or defective pluripotent stem
cells (colony-forming units, stem cells,
CFU-S) or committed stem cells (colonyforming unit, committed cells, CFU-C).
- The microenvironment may be unable to
provide for the normal development of
35
Hematology PPT Flashcards Unit 2
What is the relationship between bone marrow
and aplastic anemia?
What is the more common diagnosis for a child
with pure red cell aplasia?
TEC occurs in previously healthy children,
usually younger than 80 years of age, with most
cases occurring between what ages?
Someone that has TEC has a history of viral
infection that has been frequent within the last
past ____ months?
Is there a treatment for TEC?
In TEC, the pathogenesis appears to involve
humoral inhibition of 1)___or decreased 2)____
in many of the patients who have been studied,
but parvovirus is not a cause.
What is TEC characterized by?
In TEC, generally the bone marrow is?
How many types of congenital Dyserythropoietic
hematopoietic cells.
- The appropriate humoral and cellular
stimulators for hematopoiesis may be
absent.
- In addition, bone marrow failure could
result from excessive suppression of
hematopoietic's this by T lymphocytes or
macro phages.
- Finally, stem cells could interact among
themselves with one clone inhibiting the
growth of another.
- In most cases of aplastic anemia, it is
likely that the damage to the hematopoietic
stem cell by unknown or unknown agent in
some way alters the ability of the cell to
proliferate or differentiate.
• In most patients with acquired
aplastic anemia, bone marrow failure
results from immunologically
mediated, tissue-specific organ
destruction. New the course of the
disease can be separated into distinct
phases.
• The bone marrow is unlikely to
recover spontaneously, and most
patients die of infection or bleeding
complications within a few years.
Acquired transient erythroblastopenia of
childhood (TEC).
One and three years old
Three months
It is usually self-limited with recovery
occurring within one or two months without
therapy.
1) Erythropoiesis
2) Stem cells
A moderate to severe normocytic anemia
and severe reticulocytopenia.
Is normocellular and shows virtual absence
of erythroid precursors.
4 types of CDA
36
Hematology PPT Flashcards Unit 2
Anemia CDA
How are the 4types of CDA characterized?
What does type one CDA demonstrates?
What is the most common type of CDA?
What type of CDA has a positive acidified serum
test.
What are the erythrocytes of CDA similar to?
When does blood become acidic?
In CDA are the pathogenesis of bone marrow
failure entirely certain or not?
One hypothesis of CDA states that a foreign
agent, such as a drug or virus, may enter the body
and attach itself to?
This attachment may then provoke the body into
defending itself against what is perceived as
what?
In CDA, the patient's own body defense
mechanism may destroy what cell?
Cellular and humoral abnormalities in
hematopoietic regulation and an altered marrow
microenvironment have been implicated as
possible factors in what?
in CDA, what will happen to the patient if all
cells are involved?
In CDA, what will happen if only the red cells are
affected?
What will a bone marrow examination
demonstrate in CDA?
When did the Diamond Blackfan anemia (DBA)
first reported?
What is Diamond Blackfan anemia?
They are characterized by
hyperbilirubinemia, ineffective
erythropoiesis, and peculiarly shaped multinuclear and re-throw blasts.
A mildly macrocytic anemia with prominent
anisocytosis and poikilocytosis. New and
this form is apparent at birth and is not a
threat to life.
Type 2
Type 2
They are similar to those of patients with
PNH because the red cells in both
abnormalities are susceptible to hemolysis
in acidified normal serum.
during the night, as respirations become
more shallow.
It is not entirely certain.
Pluripotent hematopoietic stem cells.
A foreign body.
The stem cell
Aplastic anemia
The patient will have a decreased
hemoglobin, he Maddock red, and red cell
count with decreased leukocyte and platelet
counts.
Only the hemoglobin, hematocrit, and red
cell count will be affected.
The erythroid cell line and perhaps the
leukocyte and thrombocyte cell line will all
demonstrate a lack of maturational activity.
Diamond Blackfan anemia (DBA), first
reported in 1936.
is one of a group of disorders characterized
by bone marrow failure, low stature, birth
defects, and predisposition to cancer known
37
Hematology PPT Flashcards Unit 2
How many cases with Diamond Blackfan anemia
disease were reported in North America in 2010?
What was the first diagnosed of DBA?
How were the anemia and other hematologic
abnormalities being formed?
What are the central hematopoietic defected in
DBA?
When is the right time for diagnosed DBA?
What are the classic diagnosis criteria for DBA?
Is there existing evident of nonclassical cases of
DBA?
When has a patient been suffering from DBA
disease?
Is the DBA disease more common now?
What are the characteristics disorder in DBA?
What is the effect of severe anemia?
as the inherited bone marrow failure
syndromes
In 2010, there were only about 600 patients
with this disease in North America.
DBA was the first recognized inherited bone
marrow failure syndrome in which a
ribosomal disorder was identified.
Mutations in genes encoding ribosomal
proteins and the resulting defects in
ribosome biogenesis or function appeared to
be capable of causing anemia and other
hematologic abnormalities.
The central hematopoietic defects in DBA
are thought to be the hypo-proliferation of
erythroid cells and the enhanced sensitivity
of hematopoietic progenitors to apoptosis.
The majority of DBA patients are diagnosed
in the first year of life, with pallor and
lethargic he being the most common
presenting symptoms.
• anemia appearing prior to the first
birthday
• normal or slightly decreased
neutrophil count
• variable platelet counts, often
increased
• macrocytosis
normal bone marrow cellularity with few
red cell precursors
2. it is now evident that nonclassical
cases of DBA occur.
3. In patients beyond one year old,
those with mild or no anemia and
consistent congenital anomalies
may be suffering from DBA
4. DBA may be present more
commonly than previously thought,
but other causes of red cell failure
are more common.
5. The disorder is characterized by
slowly progressive and refractory
anemia, with no concurrent
leukopenia or thrombocytopenia
6. This severe anemia is
normochromic and slightly
macrocytic, reticulocyte level is
low, leukocytes are normal or
slightly decreased, platelets are
38
Hematology PPT Flashcards Unit 2
Are there any residual erythroid detected in
DBA?
How many DBA patients are respond to steroids
treatment?
What is the long-term survival rate in DBA
patients?
What is the aplastic anemia?
How many subtypes are there in Fanconi anemia
disease?
How many cases are diagnosed of childhood
aplastic anemia?
What is the characteristic of Fanconi anemia?
Is Fanconi anemia present more in male?
normal or increased, the marrow
usually shows a reduction in all
developing erythroid cells but
normal granulocytic and
megakaryocytic cell lines.
7. in a small number of cases, residual
erythroid precursors are detected.
8. Approximately 75% of patients
respond at least partially to steroids.
9. The overall long-term survival rate
is about 65%, although many
patients require long-term steroid
treatment.
10. Fanconi anemia is the best
described congenital form of
aplastic anemia.
11. There are at least 13 different
Fanconi anemia subtypes.
12. Although aplastic anemia is rare
during childhood, Fanconi anemia
occurs most frequently, accounting
for 30% of cases of childhood
aplastic anemia.
13. Fanconi anemia is inherited through
and autosomal recessive mode.
14. It is twice as common in males as in
females and can be confused with
peer red cell aplasia and
thrombocytopenia-absent radius
syndrome.
False
Iron deficiency anemia is limited to developing
countries or un developing countries. True or
False
Iron Deficiencies in children are associated
True
with infections.
True or False
An iron deficiency is a clinically significant
D
diagnosis and should be screened immediately
with:
A. Non anemic infants
B. Toddlers under 2 years of age
C. Pregnant women
All of the above
Iron Defiency has several contributing factors D
including:
A. Increased Physiological Demand, Faulty
or Incomplete Absorption
B. Excessive Loss
39
Hematology PPT Flashcards Unit 2
C. Nutritional Defiency
All of the Above
For etiological purposes an Iron Defiency can
be caused by a meat-poor diet. True or False
Can growth spurts, pregnancies, or
menstruation cause Iron Deficiencies?
Iron Deficiency Anemia was very prevalent in
the _______. Until efforts were made to
combat it. A subgroup has benifited from it.
For example, infants.
A. 1950’s
B. 1960’s
C. 1970’s
None of the above
Three subgroups remain at high risk. Identify
them.
A. Toddlers
B. Adolescent Girls
C. Women of a child bearing age
All of the above
Humans have ___ to ___ of iron per kilogram
of body weight.
The average adult has ___ to ___ of total iron.
Normal iron loss is very small, about ___ per
day.
Iron is lost the following 3 ways:
To compensate, the adult male must replace
how much iron per day?
Operational iron consists of iron used for ___
and ___.
Operational iron is found in the heme portion
of ___ and ___.
Hemoglobin contains ___% of iron in the
body.
In the normal infant at term, iron stores are
adequate to maintain iron sufficiency for
approximately ___ of postnatal growth.
In premature infants, total body iron is lower
than in the full-term newborn. They have a
faster rate of postnatal growth than infants
born at term, so unless the diet is
supplemented with iron, they become irondepleted more rapidly than full-term infants.
Iron deficiency can develop by ___ to ___
months of age in premature infants.
True
Yes
B
D
35mg to 50mg
3.5g to 5.0g
1 mg
1. exfoliation of intestinal epithelial and skin
cells 2. Through bile 3. Through urinary
excretion
1 mg
Oxygen binding and biochemical reactions.
Hemoglobin and myoglobin
Two thirds.
4 months
2-3
40
Hematology PPT Flashcards Unit 2
Breast milk and cow’s milk both contain
about ___ to ___ of iron per liter, but its
bioavailability differs significantly
The absorption of iron from breast milk is
uniquely high, about ___ on average, and
tends to compensate for its low concentration.
By contrast, only about ___ of iron in whole
cow’s milk is absorbed. About ___ of iron is
absorbed from iron-fortified cow’s milk
formulas that contain ___ of iron per liter.
Reasons for high bioavailability of iron in
breast milk are unknown.
Approximately 90% of iron from food is in
the form of iron salts and is referred to as ___
iron
The other 10% of dietary iron is in the form of
heme iron, which is derived primarily from
the ___ and ___ of meat
Sequential phases of iron deficiency:
Iron deficiency anemia often presents initially
with symptoms of:
Iron deficiency anemia in children is
associated with ___ and ___ in the first 2
years of life.
Currently, more than ___ of children in the
United States demonstrate evidence of iron
insufficiency, ___% have iron deficiency without
anemia, and
___% have iron deficiency anemia.
Which blood counts should be evaluated for IDA.
About a third of patients with IDA will present
with normal rbc morphology because:
What is the most sensitive and specific parameter
of functional iron deficiency?
A reticulocyte count equal to or greater than
___% demonstrates increased erythropoiesis.
4 chemical studies for IDA are:
Anemia of chronic disease is also known as:
Anemias can result from illness, inflammation,
0.5 to 1.0 mg
50%
10%, 4%, 12 mg
nonheme
hemoglobin and myoglobin
Stage 1 (Prelatent), Decrease in storage iron
Stage 2 (Latent), Decrease in iron for
erythropoiesis
Stage 3 (Anemia), Decrease in circulating
red blood cell parameters &Decrease in
oxygen delivery to peripheral tissues
symptoms of paleness, fatigue, and/or
weakness.
psychomotor and mental impairment
one third, 7%, 10%
Complete blood count including observation
of the peripheral blood smear, platelet count
and WBCs
They are in the early phase of iron depletion
Percentage of hypochromic RBCs
(%HYPO)
2.5%
Serum iron, Transferrin sat, serum ferritin
and soluble transferrin receptor
Anemia of inflammation
Infection, malignancy, systemic disease
41
Hematology PPT Flashcards Unit 2
___, ____ and ___.
Half of AOI/ACD are caused by ___.
Microbial agents associated with anemia of
inflammation are:
6 Other causes of AOI/ACD are:
AOI/ACD is a ___ defect not related to any
nutritional deficiency.
The principal pathogenesis of ACD is believed to
be related to ___, a small plasma protein, that is a
key molecule in controlling iron absorption and
recycling.
6 mechanisms associated with anemia of
inflammation:
What does direct bone marrow infiltration by
malignant tumor cells or by primary marrow cell
malignancies cause?
What acute-phase reactants are released in the
blood in systemic diseases that produce AOI
(anemia of inflammation)?
What initiates a common pathway of metabolic
events in response to AOI?
What is interleukin-1 specifically responsible
for?
What do laboratory assays that suggest
inflammation or infection include?
AOI is usually a mild hypoprolific anemia
What is the hematocrit range in AOI?
The peripheral blood smears usually show
normochromic and normocytic erythrocytes, but
one fourth to one third of patients display
hypochromic and microcytic erythrocytes
What do clinical chemistry studies of AOI
include?
In megaloblastic anemia, hemoglobin,
microhematocrit, and RBC are low.
What is MCV?
Subacute or chronic infections
Bacterial, fungal, viral
Neoplasms, Rheumatoid arthritis,
Rheumatic fever,
Systemic lupus erythematosus (SLE),
Uremia,
Chronic liver disease
Hypoproliferative
hepcidin
Increased hepcidin production, alterations in
Proinflammatory cytokines, hemolysis,
effects of chemotherapy, nutritional
deficiencies, blood loss
Decreased erythrocyte production
C-reactive protein, fibrinogen, haptoglobin,
ceruloplasmin
Interleukin-1 from activated macrophages
production of fever, neutrophilia,
leukocytosis, acute-phase protein synthesis,
stimulation of production of lymphokines,
and the release of lactoferrin from
granulocytes
Elevated platelet counts, elevated total
leukocyte counts, evidence of acute-phase
reactants
true
28-32%
true
Serum iron,transferrin, total iron-binding
capacity, transferrin saturation levels, serum
ferritin, soluble transferrin receptor
True
Mean corpuscular volume
42
Hematology PPT Flashcards Unit 2
MCV may be as high as ____.
What is MCH?
MCH varies but is usually ______ in 90% of
cases.
In megaloblastic anemia, a peripheral blood
smear with show moderate to significant
anisocytosis and poikilocytosis.
It will also show many macrocytic, ovalocytic red
cell precursors, notably ________.
Basophilic stippling, Howell-Jolly bodies, cabot
rings may be observed in a peripheral blood
smear.
A neutrophil is considered _______ if it contains
more than four lobes.
Platelets are also typically _____ in number.
Bone marrow is usually ________ with
megaloblastic changes in either the erythroid line
or all lines, but it can be ________ and mimic
aplastic anemia.
Erythrocyte precursors are _______ with a
_______ nuclear-cytoplasmic ratio.
Nuclear-cytoplasmic asynchrony, with relative
immaturity of the nucleoplasm, is _______.
_______ _________ may also display nuclearcytoplasmic dissociation and enlargement.
Giant __________ with with large, incompletely
segmented nuclei are characteristically seen.
The number of mitoses are ______, and the M:E
ratio is diminished to 1:1 or less.
What is the M:E ratio?
Iron store are _______, unless iron deficiency is
coincidentally present.
What is the standard treatment for vitamin B12
deficiency?
Reticulocyte count begins to increase __to__ days
after treatment and peaks in __to__ days.
Higher and later peaks occur in more ______
anemia.
________ begins to increase in approximately 1
week and will normalize within 4 to 8 weeks.
MCV typically increases for the first 3 to 4 days,
presumably because of ___________ and then
begins to decrease.
When is The normal MCV reference range is
expected to be reached?
What are the 2 major categories of megaloblastic
130 fL
Mean corpuscular hematocrit
Increased
True
Metarubricytes
True
Hypersegmented
Decreased
Hypercellular, hypocellular
Enlarged, decreased
Typical
Granulocytic precursors
Metamyelocytes
Increased
Myeloid:Erythroid ratio
Increased
Regular monthly intramuscular injections
of at least 100 mg of vitamin B12 to correct
the vitamin deficiency.
2 to 3, 5 to 8
Severe
Hematocrit
reticulocytosis
In 25 to 78 days
Vitamin B12 deficiency, Folic acid
43
Hematology PPT Flashcards Unit 2
anemia?
deficiency
What does the term megaloblastic refer to?
the abnormal marrow erythrocyte precursor
seen in processes such as pernicious anemia
true
Megaloblastic anemia reveals an abnormal
nuclear maturation and imbalance between
nuclear and cytoplasmic maturation
What is vitamin B12 deficiency associated with?
What percentage of adults over 60 years have
undiagnosed pernicious anemia?
What is the median age of diagnosis?
More men than women are affected
What would suggest a genetic predisposition to
pernicious anemia?
Pernicious anemia may be associated with
autoimmune endocrinopathies and antireceptor
autoimmune disease.
What are some hematological factors that normal
red cell maturation is dependent on ?
What occurs when one of these factors is absent?
Hemolytic disruption of the erythrocyte involves
an alteration in the erythrocytic membrane.
The causes of this membrane alteration can be
divided into inherited hemolytic disorders by the
following:
_________ and
_________ hemolytic anemia
What term refers to the site of destruction of the
red blood cell within the circulating blood?
What term refers to the site of destruction of the
red blood cell outside the circulating blood?
Inherited hemolytic disorders may affect the basic
membrane structure, the erythrocytic enzymes, or
the hemoglobin molecules within the red cell.
The ability of erythrocytes to deform and
subsequently return to their original biconcave
disc shape is determined by what?
Flexibility of the membrane relies on the
structural and functional integrity of the
________ _________.
Cytoplasmic viscosity is determined primarily by
_______.
Mutations in any of the genes coding for the
major membrane proteins can:
increased utilization of vitamin B12,
Malabsorption syndrome, Nutritional
deficiency, Pernicious anemia
1.9%
60 years
false
Gastric autoantibodies in families
true
vitamin B12 coenzymes, Folates
Megaloblastic dyspoiesis
true
Intrinsic, extrinsic
Intravascular
Extravascular hemolysis
True
Flexibility of the membrane
Cytoplasmic viscosity
Cell surface area-to-volume ratio
Membrane skeleton
Hemoglobin
Alter the amount or function of expressed
proteins
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Hematology PPT Flashcards Unit 2
What is HPP?
What is hereditary pyropoikilocytosis?
What is hereditary xerocytosis?
In vitro, the thermal instability of spectrin
suggests a defect in qualitative spectrin
abnormality.
The net loss of intracellular ____ exceeds the
passive ____, yielding a net ____ gain.
This causes the red cell to __________.
What is Rh null disease also called?
What is Rh null disease?
This disorder is associated with stomatocytosis
and spherocytosis.
What are 2 other forms of hemolytic anemia?
What is spur cell hemolytic anemia?
What is neuroacanthocytosis?
Acquired hemolytic anemia
Compromise the integrity of the membrane
Contribute to abnormal erythrocyte
morphology
Hereditary pyropoikilocytosis
It is a rare autosomal recessive disorder,
representing a subset of common hereditary
elliptocytosis HE, seen primarily in blacks.
A permeability disorder
True
K+, Na+, Na+
Dehydrate
Rh deficiency syndrome
A rare hereditary disorder causing mild,
compensated chronic hemolytic anemia
True
Spur cell hemolytic anemia
Neuroacanthocytosis
A form of acanthocyte-associated
hemolytic anemia is seen in patients with
established alcoholic cirrhosis
A heterogeneous group of
neurodegenerative disorders associated with
acanthocytosis in peripheral blood.
can be classified according to the agent or
condition responsible for inducing the
hemolysis.
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Hematology PPT Flashcards Unit 2
Example of agents and conditions associated with
acquired hemolytic anemia
46
Hematology PPT Flashcards Unit 2
Representative microorganisms associated with
hemolytic anemia
47
Hematology PPT Flashcards Unit 2
Acquired hemolytic anemia immune mechanisms
(antibodies)
Autoimmune hemolytic anemia
Some unusual aspects of the epidemiology of
AIHA are association with the following:
caused by an altered immune response
resulting in production of antibody against
the patient’s own erythrocytes, with
subsequent hemolysis. The definitive cause
of autoantibody production is unknown.
-Blood transfusion
-Immune hemolysis with allogeneic
hematopoietic cell transplantation
-Immune hemolysis with orthotopic solidorgan transplantation
Comparison of warm and cold autoimmune
hemolytic anemia
Cold-type autoimmune hemolytic anemia
associated with cold-type autoantibody (e.g.,
cold hemagglutinin disease), the
erythrocytes are usually coated with IgM.
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Hematology PPT Flashcards Unit 2
Warm- and cold-type autoimmune hemolytic
anemias
Other types of hemolytic anemia
AIHA associated with both warm and cold
autoantibodies is mediated by IgG warm
antibodies and complement as well as IgM
cold hemagglutinins.
•
•
•
Microangiopathic red cell destruction
Other examples of microangiopathies include
Paroxysmal nocturnal hemoglobinuria: etiology
Paroxysmal nocturnal hemoglobinuria:
epidemiology
Paroxysmal nocturnal hemoglobinuria:
pathophysiology
Clinical signs and symptoms
Isoimmune hemolytic anemia
Drug-induced immune hemolytic
anemia
Physical agents
DIC is one example of a microangiopathic
hemolytic anemia.
15.
-Thrombotic thrombocytopenic purpura
(TTP)
-Hemolytic uremia syndrome (HUS)
-HELLP syndrome (Hemolysis, Elevated
Liver enzyme levels, Low Platelet count)
is a rare, acquired, clonal blood disorder
caused by a nonmalignant clonal expansion
of one or more stem cell lines.
-Twenty-five percent of cases will evolve
into or from aplastic anemia.
-Approximately 5% to 10% of patients will
have terminal acute myelogenous leukemia.
-The median age of patients at diagnosis is
42 years (range, 16 to 75 years).
-Median survival after diagnosis is 10 years.
Spontaneous long-term remission can occur.
Mutations occur in a gene termed PIG-A
and result in the failure to present a large
class of proteins on the hematopoietic cell
surface
-PNH begins insidiously in patients between
the age of 30 and 60 years.
-Irregular episodes of hemoglobinuria
associated with sleep are a startling
manifestation of this disorder.
less than 6 g/dL.
Most patients have severe anemia with
hemoglobin concentrations
Peripheral blood smears may reveal hypochromic, an iron deficiency state has developed to
microcytic red cells if
cell lysis
Autohemolysis
is increased after 48 hours, and hemolysis
may increase with the addition of glucose to
the test. Both the sucrose hemolysis (sugarwater) test and Ham test (acid-serum lysis)
are diagnostic procedures.
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Hematology PPT Flashcards Unit 2
Hemosiderinuria
The diagnosis of PHN
is increasing
Hemoglobin defect
SCD and -thalassemias
These hemoglobin mutations occur at high
incidences in these regions because
-are inherited single-gene disorders that affect the
amino acid residual sequence or production of
normal hemoglobin
-It is estimated that around 7% of the world
population carries a globin-gene mutation, and in
the majority of cases, it is inherited as an
autosomal recessive trait. Disorders associated
with autosomal recessive genes need to be in the
homozygous state to produce the disease.
-Some disorders are caused by the inheritance of
an autosomal dominant gene that will produce
hemolytic disease in its heterozygous state.
Hemoglobinopathies may have a hemolytic
manifestation.
Although hemoglobinopathies and thalassemias
are two genetically distinct disease groups
In the genetic manifestation of the
hemoglobinopathies, the distinction between the
disease state and the trait condition is made.
the excretion of an iron-containing pigment
derived from hemoglobin on disintegration
of red cells, is a classic manifestation of
chronic intravascular hemolysis.
The use of flow cytometry for
immunophenotyping erythrocytes is
increasing
-is the least common type of AIHA
-It is transient and self-limiting but can
produce serious hemolysis of erythrocytes.
-It occurs almost exclusively in children in
association with viral disorders.
The hemoglobinopathies encompass a
heterogeneous group of disorders associated
with genetic mutations in both the α-globin
and β-globin genes.
are the most common monogenic diseases
of man. They are found in the “malaria belt”
that extends from the Mediterranean and
sub-Saharan Africa through Southeast Asia
and southern China.
heterozygotes have a selective advantage
against infection with Plasmodium
falciparum
Hemoglobinopathies, for example, SCD
Approximately 25% of all
hemoglobinopathies demonstrate the
decreased red cell survival due to red cell
membrane deformity that characterizes
hemolytic disease.
the clinical manifestations of both include
anemia of variable severity and variable
pathophysiology
Disease versus trait
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Hematology PPT Flashcards Unit 2
A disease
A trait
Abnormal hemoglobins including
hemoglobinopathies and thalassemias can be
classified into three major categories:
In sickle cell disease, what other RBC form is
commonly present, other than drepanocytes
(sickles)?
What are acceptable, reliable, and accurate
methods of testing for sickle cell disease?
An alternate method for sickle cell testing that is
expensive and limited in the number of genotypes
that it can identify is known as?
What tests are performed on a suspected sickle
cell patient to obtain a definitive diagnosis?
At how many weeks gestation can fetal diagnosis
of sickle cell disease be determined through
amniocentesis?
Which test allows DNA diagnosis to be
performed at the 7th to 10th week of gestation.
what is the most abundant form of hemoglobin in
a newborn?
what is the normal hemoglobin distribution in a
normal term infant?
Adult normal Hemoglobin A has 2 alpha and 2
beta chains, what is fetal hemoglobin (Hb F)
made up of?
During which trimester is there a progressive
is defined as either the homozygous
occurrence of the gene for the abnormality
or the possession of a heterozygous,
dominant gene that produces a hemolytic
condition
is described as the heterozygous and
normally asymptomatic state. In the case of
sickle cell anemia, the trait must be
inherited from both parents
-Abnormal molecular structure of one or
more of the polypeptide chains of globulin
in the hemoglobin molecule, for example,
sickle cell anemia
-A defect in the rate of synthesis of one or
more particular polypeptide chains of
globulin in the hemoglobin molecule, for
example, the thalassemias
-Disorders that are a combination of
abnormal molecular structure with a
synthesis defect, for example, Hb E–βthalassemia
Target cells (codocytes)
Hemoglobin electrophoresis, IEF, and
HPLC
Globin DNA analysis
-Reassessment of the hemoglobin phenotype
-Measurement of hemoglobin concentration
and red cell indices
-Inspection of red cell morphology
-Correlation of laboratory findings with the
clinical history
14 weeks
chorionic villus biopsy
Hemoglobin F (fetal hemoglobin)
80% Hb F and 20% Hb A in a normal term
infant
Hb F is composed of two α- and two γglobulins
During the last trimester (3rd)
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Hematology PPT Flashcards Unit 2
increase in β-globin synthesis and a decrease in γchain synthesis.
True or False
In a normal term infant, approximately 80% of
the non-α globulin is γ-globin and 20% is βglobin.
True or False
Screening for SCD in newborns at birth is
mandated in all 50 states and the District of
Columbia.
Sickle cell disease affects 1 in 375 African
American newborns a year. Without quick
diagnosis and prophylactic antibiotics with
pneumococcal conjugate vaccination before 2
months of age what are the newborns with sickle
cell disease vulnerable to?
Screening tests will identify approximately 50
sickle cell carriers for every infant diagnosed with
SCD. What type of hemoglobin is expected with
an infant with sickle cell trait?
Which hemoglobin is always in more abundance
in infants with sickle cell trait? Why?
True
True
life-threatening pneumococcal infections
Hb F, Hb A, Hb S
Hb A
because α chains preferentially pair with
normal β chains
True
True or False
The initial sickle cell screen performed after birth
isn't conclusive and a confirmatory test should
always be performed on an infant no later than 2
months of age.
For hemoglobin screening, blood collected by
At least 1 week at room temperature
heel stick onto filter paper remains stable for how
long?
what tests are commonly used in the United States Thin Layer Isoelectric Focusing (IEF), or
for sickle cell screening?
High Performance Liquid Chromatography
(HPLC)
What part does the clinical lab take in monitoring -Monitoring the severity of the anemia and
sickle cell disease?
transfusing blood only when necessary
-Testing to help diagnose organ failure.
(recurrent vasoocclusion and its associated
vasculopathy result in significant
progressive organ failure.)
What is the only potential cure for sickle cell
Bone marrow transplant
disease?
What is most probable reason the Hb S mutation
Sickle cell trait provides a survival
has remained somewhat common in people with
advantage over individuals with normal
African descent?
hemoglobin in regions where malaria, P.
falciparum, is endemic
what hemoglobin disorder is becoming an
Thalassemia
increasing public health issue and is expected to
52
Hematology PPT Flashcards Unit 2
become increasingly identified in many parts of
the world where it has previously not been seen?
which thalassemia’s account for much of the
projected increase?
which thalassemia is one of the most frequent
hemoglobinopathies worldwide, reaching 60% of
the population in many regions of Southeast
Asia?
Which thalassemia diseases often considered
benign, are now recognized to be more severe
than originally reported.
what is the cause of thalassemia?
How does thalassemia differ from sickle cell?
Inheritance of thalassemia is?
Thalassemias are characterized by the ____ or
____ in the synthesis of one of the two constituent
globin subunits of a normal hemoglobin
molecule.
In α-thalassemia, decreased synthesis of ____
results in accelerated red cell destruction because
of the formation of insoluble Hb H inclusion in
the mature erythrocyte.
The more severe ____ reflects the extreme
insolubility of α-globin, which is present in
excess in the red cell because of decreased βglobin synthesis.
Studies of RNA metabolism in erythroid cells
have suggested that many patients with ____ have
a defect in RNA processing. This defect affects
efficient RNA splicing during protein globin
synthesis.
one of the most common single-gene disorders.
This type of thalassemia can occur due to any of
200 or more single-gene point mutations which
result in the decrease in production if β-globin.
The reduction in β-globin results in an increase of
what? And what does this cause?
ineffective erythropoiesis found in β-thalassemia
is now thought to occur do to?
In β-thalassemia, hematological findings include.
Hb E–β-thalassemia and Hb H disease
Hb E–β-thalassemia
α-thalassemia diseases
an abnormality in the rate of synthesis of the
globin chains
Thalassemia is caused by an abnormality in
the rate of synthesis of the globin chains.
Whereas sickle cell is due to an inherited
structural defect in one of the globin chains
that produces hemoglobin with abnormal
physical or functional characteristics.
Autosomal
absence, decrease
α-globulin
β-thalassemia
α-thalassemia
β-thalassemia
β-thalassemia
α-globin chains, causing ineffective
erythropoiesis and reduced red cell survival
Accelerated apoptosis of the red blood cells
Decreased hemoglobin
Decreased hematocrit
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Hematology PPT Flashcards Unit 2
What would the hemoglobin concentration be for
someone with β-thalassemia?
What type of RBC's would be found in a blood
smear from someone with β-thalassemia?
how would the red cell indices appear with a
blood sample from a patient with β-thalassemia?
In a patient with β-thalassemia, what would you
expect the RDW to be? Why?.
Knowing the disease state and processes of βthalassemia, what would be expected of the
following tests?
Reticulocyte count
Osmotic fragility of RBC
Bilirubin
Serum iron
TIBC
why is the soluble transferring receptor index test
more specific than serum ferritin test?
In β thalassemia, hemoglobin electrophoresis
reveals an change in which two hemoglobins?
A variable form of homozygous α thalassemia
demonstrates changes in which hemoglobins?
Why is there an absence of Hb A is this situation?
Heterozygous β thalassemia could be mistaken for
what condition on a peripheral blood smear?
What are some other laboratory findings?
What is the ideal time period for prenatal
diagnosis of β Thalassemia?
How is this test preformed?
Why is second trimester fetal blood analysis
done?
When were methods developed to perform
diagnostic testing before implantation in high-risk
patients?
What is preimplantation genetic diagnosis
(PGD)?
Decreased red cell count
2-3g/dL
anisocytosis, poikilocytosis, hypochromia,
target cells, polychromatophilia, and few to
many nucleated red cells Erythrocytes are
significantly microcytic and hypochromic
All indices will be reduced
The RDW would be increased due to
anisocytosis
increased reticulocyte formation (5% to
10%)
decreased osmotic fragility
moderately increased bilirubin
increased serum iron
Increased saturated total iron-binding
capacity (TIBC).
because serum ferritin may be increased due
to other pathology
An increase in Hb F and decrease in Hb A.
There is no Hb A, an increase in Hb A2, and
a decrease in Hb F.
Because there is an absence of β Chains
A mild iron deficiency anemia
Decreased MCV, Increased Hb A2 on
electrophoresis and decreased osmotic
fragility
First trimester
Chorionic villus tissue is used for DNA
analysis by PCR to detect point mutations or
deletions.
It is done to estimate the relative rates of
synthesis of globin chains of hemoglobin
and then base the diagnosis on the beta to
alpha biosynthetic ratio
In the early 1990s
It involves performing conventional in vitro
fertilization followed by extracting one or
two cells from the resulting blastomeres on
day 3. PCR is used to detect thalassemia
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Hematology PPT Flashcards Unit 2
PGD has been extended to HLA typing of
embryonic biopsies. What has this allowed for?
Why is testing for hemoglobinopathies
incorporated into existing programs?
What are the initial screening methods used?
If an abnormal is identified what information is
helpful in guiding the sequence of diagnostic tests
for specifics?
What treatment is required for severe anemias?
mutation within the cells. Unaffected cells
are selected for implantation
This allows for the selection of an embryo
that is not affected by thalassemia and that
may also serve as a stem cell donor or a
previously affected child in the same family.
This can be ethically controversial or even
illegal in some contries.
There is an increase in the prevalence of
hemoglobinopathies in the United States.
Most screening programs employ HPLC or
IET as the preferred first-line technique to
make a presumptive diagnosis of a clinically
significant hemoglobinopathy.
Ethnicity information and parental studies
Blood transfusion, bone marrow, or PSC
transplant
How can homozygous β thalassemia be
Careful counseling and prenatal diagnosis in
prevented?
Sardinia reduced the incidence of
homozygous β Thalassemia by more than 90
percent.
What is the cause of α Thalassemia?
In contrast to β Thalassemia with most cases
caused by point mutations, the major cause
of α thalassemia is deletion that remove one
or both α globulin genes from the affected
chromosome 16
What are the four types of α Thalassemias based
1) Silent carrier state (one inactive α
on genotype and the total number of abnormal
gene)
genes that result?
2) Α Thalassemia trait (two inactive α
genes)
3) Hb H disease (Three inactive α
genes)
Hydrops fetalis with Hb Bart (four inactive
α Genes)
Which hemoglobinopathy is prevalent in the same Hemoglobin C disease
geographic area as Hb S (sickle cell) disease?
How does Hb C differ from Hb A?
It differs by the substitution of a single
amino acid residual, Lysine, for Glutamic
acid in the sixth position from the amino
NH2 terminal end of the beta chain.
This is the exact point of substitution of Hb S. So The amino acid is different
how is it different?
What disorder results from the inheritance of one Hemoglobin SC disease
gene for Hb S from one parent and one gene for
Hb C from the other parent?
How is SCD different from Hemoglobin SC
The course of the disease is usually milder
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Hematology PPT Flashcards Unit 2
disease?
What are the clinical signs and symptoms?
Hb D has several variants. What are the
symptoms of patients who are homozygous or
heterozygous?
What kind of cells may be seen on
examination of a peripheral blood smear?
Which hemoglobinopathy occurs with the
greatest frequency in southeast asia?
In Thailand what is the frequency of the
Hb E trait?
When do Hb E syndromes appear?
than SCD although Hb C tends to aggregate
and potentiate the sickling of Hb S
They are similar to mild sickle cell anemia.
Lab examination of a peripheral blood
smear usually reveals target cells, folded
erythrocytes, and occasionally intracellular
crystals
They are asymptomatic
Target cells
Hemoglobin E disease
Almost 50 percent
Syndromes appear in homozygous and
heterozygous forms. They also appear as
compound heterozygotes in combination
with alpha and beta thalassemias, and other
structural variants
What amino acid substitution causes Hb
The substitution of lysine for glutamic acid
E?
in the beta chain of hemoglobin.
What are the clinical presentations of Hb
Clinical presentation is diverse. It can range
E?
from entirely asymptomatic to mildly
anemic to severely anemic.
What is Hb H?
It is a mild to severe chronic hemolytic
anemia.
What causes Hb H?
It frequently results from an absence of
three of the four alpha-globin genes.
In what regions does Hb H primarily
1) Southeast Asia
affect individuals?
2) Mediterranean islands
3) Parts of the middle east
Why has the prevalence of Hb H increased Because of the large influx of immigrants
in the United States?
from southeast Asia in the past 20-30 years
What is methemoglobinemia (Hb M)?
It is a disorder associated with elevated
methemoglobin levels in the circulating
blood
What are the causes of
1) Toxic substances
methemoglobinemia?
2) Hb M variants
3) NADH methemoglobin reductase
(also called diaphorase) deficiency
How many variant forms does Hb M
It has five variant forms.
have?
What is the process by which Hb M
It has a dominant inheritance resulting from
affects the body?
a single substitution of an amino acid in the
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Hematology PPT Flashcards Unit 2
What are unstable hemoglobins?
How are most unstable hemoglobins
acquired?
What does this unstable hemoglobin
cause?
What are Heinz bodies associated with?
Tetramers of normal chains, such as Hb Bart and
Hb H, appear in what disease?
What is Hb F?
Is expression in adult life normal?
What is the level of expression?
What is the abnormality referred to as?
What are normal adult hemoglobin components?
What is Sickle Cell Disease?
What is Sickle cell anemia (Hb SS)?
What is the most common form of
hemoglobinopathy?
Hb S is different from Hb A because of?
In which ethnic background is SCD most
commonly found?
What occurs under conditions of extremely
reduced oxygen and increased acidity in the
blood?
What happens when sickling occurs?
globin chain that stabilizes iron in the ferric
form. NADH-diaphorase is the enzyme that
reduces cytochrome b5, which converts
naturally occurring ferric iron back to the
ferrous state
Unstable hemoglobins are hemoglobin
variants in which amino acid substitutions
or deletions weaken the binding forces that
maintain the internal portion of the globin
chains of the hemoglobin molecule
They are inherited as autosomal dominant
disorders
May cause abnormal hemoglobin to
denature and precipitate in erythrocytes
such as Heinz bodies of an oxidizing drug
or an infection
They are associated with alpha or beta
chain abnormalities.
Thalassemias
Fetal hemoglobin
No
15%-30% of the total hemoglobin
Hereditary persistence of Hb F
Hb A (95% to 98%), Hb A2 (2% to 3%), Hb
A1 (3% to 6%), and fetal hemoglobin (Hb F)
(<1%). The major fraction is Hb A
SCD is a general term for abnormalities of
hemoglobin structure in which the sickle
gene is inherited from at least one parent
Is an expression of the inheritance of a
sickle gene from both parents
Sickle cell anemia
A single nucleotide change (GAT to GTT)
that results in the substitution of valine for
glutamic acid at the sixth position on the 
chain of the hemoglobin molecule.
African ancestry, but it also affects persons
of Mediterranean, Caribbean, South and
Central American, Arab, and East Indian
ancestry.
Polymerization of Hb S
It subsequently leads to an increased mean
57
Hematology PPT Flashcards Unit 2
What leads to repeated cycles of sickling and
unsickling?
What is the adherence of sickled erythrocytes to
the vascular endothelium?
What cause by recurrent obstruction of the
microcirculation by intravascular sickling?
What splenic dysfunction is a potentially lifethreatening complication that develops during
infancy?
What is the most frequent cause of death in
patients younger than 5 years?
In what age does vasoocclusive disease develops?
In pregnancy, there is no increase in disease
manifestation but there is an increase in the
following:
The two main causes of erythropoietic
suppression are the following:
Aplastic crises result from which virus infection?
What is a significant cause of death in patients of
all ages who have sickle cell anemia?
What percentage of patients with sickle cell
anemia survive beyond the fifth decade?
What are the general signs and symptoms of
sickle cell anemia?
What can be seen on peripheral smears if patient
is in acute crisis state?
What are the laboratory features?
corpuscular hemoglobin concentration
(MCHC) in proportion to the number of
molecules in the deoxygenated state.
Deoxyhemoglobin S is less soluble than
deoxyhemoglobin A or oxyhemoglobin S.
RBC’s becoming permanently damaged.
Vasoocclusion
Acute crises
Sickle cell anemia
Infectious crises
Between the ages of 12 months and 6 years.
Maternal mortality of 20%
Fetal mortality of 20%
Aplastic crises
Megaloblastic erythropoiesis
Parvovirus
Acute chest syndrome
50%
Pain
Pulmonary complications
Stroke
Sickled red cells (drepanocytes)
•
•
•
•
•
•
•
Reticulocytosis (8% to 12%)
An increased mean corpuscular
volume (MCV) to levels up to 100
fL
Elevated serum; unconjugated
bilirubin and methemalbumin
Decreased serum haptoglobin and
hemopexin
Increased serum lactate
dehydrogenase (LDH)
Mildly increased aspartate
transaminase (AST)
Increased urine urobilinogen
58