Chapter Review
erythrocytic indices are typically
Turgeon, M. (2012). Clinical Hematology:
Theory and Procedures. Sixth Edition.
Lippincott Williams & Wilkins. China
Chapter 10:
Iron Deficiency Anemia and Anemia of
Chronic Inflammation
● The etiology of Iron Deficiency
Anemia is :
○ Nutritional deficiency
○ Faulty iron absorption
○ Excessive loss of iron
● Iron Deficiency anemia is still
common in:
○ Toddlers
○ Adolescent girls
○ Women of childbearing age
● Decrease iron intake
○ Meat poor diet
● Faulty iron absorption
○ Sprue
● Pathological iron loss
○ Colon cancer
● Physiological iron loss
○ Menstruation
● Increased iron utilization
○ Adolescent growth spurt
● The average adult has 3.5g to 5.0g
of total iron.
● The most functional iron in humans
is found in hemoglobin molecules of
erythrocytes (RBCs).
● Approximately 90% of iron from food
is in the form of nonheme iron.
● Most ingested iron is readily
absorbed into the body in the
duodenum and upper jejunum.
● Transferrin represents:
○ Beta globulin that moves iron
○ Glycoprotein that moves iron
● In iron deficiency anemia, the
MCV decreased, MCH decreased
and MCHC decreased.
● The peripheral blood smear
demonstrates microcytic,
hypochromic red blood cells in IDA.
● In IDA, the serum iron is severely
decreased and the TIBC is
increased.
● Anemias of inflammation/chronic
diseases can be caused by:
○ Inflammation
○ Infection
○ Malignancy
● AOI can result from:
○ Inappropriately decreased
erythropoietin
○ Suppression of
erythropoiesis by cytokines
from activated macrophages
and lymphocytes
○ Impaired iron metabolism
● The typical peripheral blood film of a
patient with AOI typically reveals
normocytic, normochromic
erythrocytes.
● Leukoerythroblastosis can appear as
immature leukocytes and
erythrocytes.
● The most appropriate treatment for
AOI is treatment of the inflammatory
condition.
● Sideroblastic anemia can be caused
by:
○ Congenital (chromosomal)
defect
○ Drugs (e.g.,
chloramphenicol)
○ Association with malignant
disorders (e.g., acute
myelogenous leukemia)
● The common feature of sideroblastic
anemia is ringed sideroblasts.
 ● The greatest portion of operational
body iron is normally contained in
hemoglobin.
● Storage iron in the human body is:
○ Found in hepatocytes
○ Found in macrophages
○ Sequestered as ferritin
● The most sensitive assay for the
diagnosis of hereditary
hemochromatosis (HH) is transferrin
saturation.
Chapter 11
Megaloblastic Anemias
● Megaloblastic anemias can be
caused by:
○ Tapeworm infestation
○ Gastric resection
○ Nutritional deficiency
● Megaloblastic anemia related to folic
acid deficiency is associated with:
○ Abnormal absorption
○ Increased utilization
○ Nutritional deficiency
● The underlying type A gastritis that
causes pernicious anemia is
immunologically related to:
○ Autoantibody to IF
○ Autoantibody to parietal cells
● Cobalamin transport is mediated by:
○ IF
○ TC II
○ R proteins
● In megaloblastic anemia, the typical
erythrocytic indices are MCV
increased,MCH increased and
MCHC normal.
● The peripheral erythrocyte
morphology in folate deficiency is
similar to pernicious anemia, and the
RBCs are large.
● In a case of classic pernicious
anemia, the patient has:
○ Leukopenia
○ Hypersegmented neutrophils
○ Anemia
● The reticulocyte count in a patient
with untreated pernicious anemia is
characteristically <1.0%.
● The following clinical chemistry
assays with their expected value in
pernicious anemia:
○ Serum Haptoglobin-binding
capacity
■ Decreased
○ Serum B12
■ Decreased
○ Folate
■ Normal
○ Serum iron
■ Increased
○ Percent Transferrin
■ Increased
○ Serum LDH
■ Significantly
increased
○ Unconjugated bilirubin
■ Increased
Chapter 12
Hemolytic Anemias
● Hemolytic disruption of the
erythrocyte involves an alteration in
the erythrocyte membrane.
● Intravascular hemolysis
○ Destruction of RBCs within
the circulatory blood
● Extravascular hemolysis
○ Destruction of RBCs outside
the circulatory blood
● The following tests are useful in
determining increased erythrocyte
destruction:
○ Reticulocyte count
○ Serum haptoglobin
○ Unconjugated bilirubin
● The following disorders are matched ● The most common glycolytic
with their appropriate category: enzyme deficiency associated with
○ G6PD deficiency the aerobic pathway of erythrocyte
■ Erythrocytic enzyme metabolism is G6PD.
defect ● The most common glycolytic
○ Hereditary spherocytosis enzyme deficiency associated with
■ Structural membrane the anaerobic pathway of
defect erythrocyte metabolism is Pyruvate
○ Thalassemia kinase.
■ Defect of the ● The laboratory assay that would
hemoglobin molecule specifically indicate a deficiency of
○ Pyruvate kinase (PK) G6PD enzyme is Heinz bodies on
deficiency peripheral blood smears.
■ Erythrocytic enzyme ● The enzyme deficiency that causes
defect methemoglobinemia is NADH-
○ Hereditary spherocytosis methemoglobin reductase.
■ The most common ● Acquired hemolytic anemia can be
prevalent hereditary caused by:
hemolytic anemia ○ Chemicals or drugs
among people of ○ Infectious organisms
Northern European ○ Antibody reactions
descent ● The infectious microorganism
○ Hereditary elliptocytosis directly associated with hemolytic
■ An overabundance of uremic syndrome is E. coli O157-H7.
oval-shaped red cells ● The following acquired hemolytic
○ Hereditary pyropoikilocytosis anemias:
(HPP) ○ Warm-type autoimmune
■ A subgroup of hemolytic anemia (AIHA)
common hereditary ■ Rh antibodies are the
elliptocytosis most frequent cause
○ Hereditary stomatocytosis ○ Cold-type AIHA
■ Can be seen in the ■ IgM, usually anti-I
genetic hemoglobin ○ Isoimmune hemolytic anemia
defect, thalassemia ■ Usually occurs in
○ Hereditary xerocytosis newborn infants
■ A permeability ● The erythrocyte alteration
disorder characteristically associated with
● Heinz bodies are associated with the hemolytic anemias is burr cells.
congenital hemolytic anemia, G6PD ● The following are laboratory
deficiency. procedures that would reflect a
● A hemolytic crisis may be typical hemolytic anemia:
precipitated in 10% of American ○ Increased osmotic fragility
black males suffering from G6PD ○ Increased total serum
deficiency by primaquine. bilirubin
 ○ Increased reticulocyte count,
unless hematopoiesis is
suppressed
● The following are associated with
hemolytic anemia:
○ Decreased hemoglobin and
packed cell volume
○ Increased reticulocyte count
○ Decreased erythrocyte
survival
● Paroxysmal nocturnal
hemoglobinuria exhibits sensitivity of
one population of red blood cells to
complement.
● Paroxysmal nocturnal
hemoglobinuria episodes are usually
associated with sleep.
● The defect in PNH probably is a
structural protein associated defect
of the red cell membrane.
Chapter 13
Hemoglobinopathies and Thalassemias
● The common denominator in the
hemoglobinopathies is that all are
inherited or genetic defects related
to hemoglobin.
● Hemoglobinopathies can be
classified as:
○ Abnormal hemoglobin
globulin structure
○ A defect of hemoglobin
globulin synthesis
○ A combination of defects of
both structure and synthesis
● Normal adult hemoglobin contains
the following components: Hb A
(95% to 98%), Hb A2 (2% to 3%),
Hb A1 (3% to 6%), and Hb F (<1%).
● In the hemoglobinopathies, a trait is
described as heterozygous and
asymptomatic.
● In sickle cell anemia the cause is:
○ A change of a single
nucleotide (GAT to GTT)
○ The substitution of valine for
glutamic acid at the sixth
position on the beta chain of
the hemoglobin molecule
● In sickle cell disease the abnormality
is related to an abnormal molecular
structure of hemoglobin.
● One of the two most common
monogenetic diseases of man is
sickle cell anemia.
● If a patient with sickle cell anemia is
in an acute crisis state, peripheral
blood smears may exhibit
drepanocytes.
● Estimated percentage of black
Americans are heterozygous for Hb
S is 8%.
● Factors that contribute to the sickling
of erythrocytes in sickle cell anemia
crisis are extremely reduced oxygen
and increased acidity in the blood.
● The most common complaint
associated with sickle cell anemia
acute pain.
● Thalassemias are characterized by
absence or decrease in synthesis of
one or more globlin subunits.
● Homozygous b-thalassemia patients
have severe transfusion-dependent
anemia.
● In a-type thalassemia, with three
inactive a genes, Hb H is a
characteristic.
● The primary risk to thalassemia
major patients who receive frequent
and multiple blood transfusions is
iron overload.
● The peripheral blood smear in silent
state patients with a-thalassemia
typically appears as normochromic,
normocytic.
 ● The characteristic hemoglobin
concentration in a patient’s silent
state with heterozygous b-
thalassemia is Hb A level normal.
● Deoxyhemoglobin C has:
○ Decreased solubility
○ The ability to form
intracellular crystals
● The incidence of Hb E
hemoglobinopathy is highest in
Southeast Asia.
● Most unstable hemoglobins:
○ Are inherited autosomal
dominant disorders
○ Result from amino acid
substitutions or deletions
○ Are hemoglobin variants
Rodak, B. et al. (2007). Hematology:
Clinical Principles and Applications. Third
Edition. Saunders Elsevier. St. Louis,
Missauri.
CHAPTER 18
Anemias: Red Blood Cell Morphology and
Approach to Diagnosis
● All of the following are clinical signs
or symptoms of anemia:
○ Fatigue
○ Jaundice
○ Eating unusual things such
as ice
● The RBC index that is used to
describe average RBC volume is the
MCV.
● Variation in RBC volume is
expressed by the RDW.
● There is an anemia that develops
because the bone marrow becomes
scarred. As a result, the amount of
active bone marrow is diminished,
including RBC precursors. The cells
that are present are normal, but
there are too few to meet the
demand for blood cells, and anemia
develops. The reticulocyte count is
low. This anemia would be
described as insufficient
erythropoiesis.
● The elevation which points to
reduced RBC life span and
hemolytic anemia is the reticulocyte
count.
● An elevated MCV, along with a high
RDW suggests vitamin B12 or folate
deficiency.
● Poikilocytosis Is only detectable by
examination of a peripheral blood
smear.
● Folate deficiency would be within the
differential diagnosis of a patient
with an MCV of 115 FL and an RDW
of 20% (reference range 11.5 -
14.5).
● When anemia is long standing,
reduced oxygen affinity of Hb is
among the adaptations of the body.
● Among a newborn boy, an adult
woman, an adult man, and a 10-year
old-girl, the patient that would be
considered with an Hb value of 14.5
g/dL is the newborn boy.
CHAPTER 19
Disorders of Iron and Heme Metabolism
● The mother of a 4-month-old infant
who is being breastfed sees her
physician for a routine postpartum
visit. She expresses concern that
she may be experiencing
postpartum depression because she
does not seem to have any energy.
Although the physician is
sympathetic to the patient’s concern,
she orders a CBC and iron studies
seeking an organic explanation for
the patient’s symptoms. The results
are as follows:
CBC:All results within reference
range except RDW = 15 %.
Total iron: decreased
Iron-binding capacity: increased
% saturation: decreased
Ferritin: decreased
Based on the patient’s laboratory
and clinical findings, it can be
concluded that the patient is in stage
2 of iron deficiency, before frank
anemia develops.
● A bone marrow biopsy was
performed as part of the cancer
staging protocol for a patient with
Hodgkin lymphoma. Although no
evidence of spread of the tumor was
apparent in the marrow, other
abnormal findings were noted.,
including a slightly elevated myeloid-
to-erythroid ratio. White blood cell
and RBC morphology appeared
normal, however. The Prussian blue
stain showed abundant stainable
iron in the marrow macrophages.
The patient’s CBC revealed an Hb of
10.8 g?dL, but RBC indices were
within reference ranges. RBC
morphology was unremarkable.
These findings would be consistent
with anemia of chronic inflammation.
● It can be predicted that the iron
study results for the patient with
Hodgkin disease described in the
2nd bullet, is as follows:
○ Total Iron: Decreased
○ Iron Binding: Decreased
○ % Saturation: Decreased
○ Ferritin: Increased
● A 35-year-old Caucasian woman
saw her physician, complaining of
headaches, dizziness, and nausea.
The headaches had been increasing
in severity over the last 6 months.
This was coincident with her move
into an older house built about 1900.
She had been renovating the house,
including stripping paint from the
woodwork. Her CBC results showed
a mild hypochromic, microcytic
anemia with polychromasia and
basophilic stippling noted. Serum
lead test would be the most useful
in confirming the cause of her
anemia.
● In men and postmenopausal women
whose diets are adequate, iron
deficiency anemia most often results
from chronic gastrointestinal
bleeding.
● Among a 15-year-old boy who eats
mainly fast food and junk food, a 37-
year-old woman who has never
been pregnant and amenorrhea, a
63-year-old man with reactivation of
tuberculosis from his childhood, and
a 40-year-old man who lost blood
during surgery to repair a fractured
 leg, the individual who is at greatest
risk for development of iron
deficiency anemia would be the 15-
year-old boy who eats mainly fast
food and junk food.
● Among a 15-year-old girl with
asthma, a 40-year-old woman with
type 2 diabetes mellitus, a 65-year-
old man with hypertension, and a
40-year old man with severe
rheumatoid arthritis, the individual
who is at greatest risk for the
development of anemia of chronic
inflammation would be the 30-year-
old man with severe rheumatoid
arthritis.
● Transferrin saturation assay can be
used cost-effectively in screening for
hereditary hemochromatosis.
● In the pathogenesis of the anemia of
chronic inflammation, hepcidin levels
increase during inflammation and
reduce iron absorption from
enterocytes.
● Sideroblastic anemias are anemias
that result from failure to incorporate
iron into protoporphyrin IX.
CHAPTER 20
Anemias Caused by Defects of DNA
Metabolism
● The findings which are consistent
with a diagnosis of megaloblastic
anemia are:
○ Absolute decrease of
neutrophils
○ Increased RDW
○ Increased serum lactate
dehydrogenase
● A patient has a picture of
megaloblastic anemia. The folate
level is decreased, and the vitamin
B12 is normal. The expected value
for the methyl-malonic acid assay
would be normal.
● The statements that characterize the
relationships among macrocytic
anemia, megaloblastic anemia, and
pernicious anemia are as follows:
○ Megaloblastic anemia is
macrocytic.
○ Pernicious anemia is
macrocytic.
○ Pernicious anemia is
megaloblastic.
● Hypersegmentation of neutrophils is
the CBC finding most suggestive of
a megaloblastic anemia.
● The following is a description of a
bone marrow smear:
The marrow appears hypercellular
with a myeloid-to-erythroid ratio of
1:1 due to prominent erythroid
hyperplasia. Megakaryocytes appear
normal in number and appearance.
The WBC elements appear larger
than normal with especially large
metamyelocytes, although they
otherwise appear morphologically
normal. Teh RBC precursors also
appear large. There is nuclear-
cytoplasmic asynchrony, with the
nucleus appearing more mature than
expected for the color of the
cytoplasm.
 The statement that is inconsistent
with the expected picture of
megaloblastic anemia is the
statement indicating that RBC
nucleus are more mature than the
cytoplasm.
● The following findings would be
consistent with elevated levels of
parietal cell antibodies:
○ Hypersegmentation f
neutrophils
○ Macrocytic RBCs
○ Elevated levels of intrinsic
factor blocking antibodies
● Holotranscobalamin II is the most
metabolically active form of
absorbed vitamin B12.
● Folate and vitamin B12 work
together in production of DNA.
● The macrocytosis associated with
megaloblastic anemia results from
reduced numbers of cell divisions.
● Individuals who descended from the
Northern European ethnic/racial
group are at higher risk for
pernicious anemia.
CHAPTER 21
Bone Marrow Failure
● The clinical consequences of
pancytopenia include:
○ Fatigue
○ Infection
○ Bleeding
● Idiopathic, acquired aplastic anemia
is due to a drug reaction.
● The pathophysiologic mechanism is
acquired, idiosyncratic aplastic
anemia is the destruction of stem
cells by autoimmune T cells.
● The aplastic anemia classification of
a patient with a bone marrow
cellularity of 10%, a Hb of 7 g/dL, an
absolute neutrophil count of
0.1 x 1 09 /L and a platelet count of
10 x 1 09 /L is very severe.
● The most consistent peripheral
blood findings in severe aplastic
anemia are:
○ Macrocytosis
○ Thrombocytopenia
○ Neutropenia
● The treatment that has shown the
best success rate in young patients
with severe aplastic anemia is stem
cell transplant from an HLA-identical
sibling.
● The test that is most useful in
differentiating Fanconi anemia from
other causes of pancytopenia is
Diepoxybutane-induced
chromosome breakage.
● Mutations in genes that code for the
telomerase complex may include
bone marrow failure by premature
death of stem cells.
● Diamond-Blackfan anemia differs
from inherited aplastic anemia in that
in the former, only erythropoiesis is
affected.
● The anemia that should be
suspected in a patient with refractory
 anemia, hemosiderosis, and
multinuclearity of erythrocyte
precursors in the bone marrow is
CDA (Congenital dyserythropoietic
anemia).
● The pathophysiology of anemia of
chronic renal disease is mainly due
to inadequate production of
erythropoietin.
CHAPTER 22
Introduction to Increased Destruction of
Erythrocytes
● The term hemolytic disorder in
general refers to a disorder in which
there is an increased destruction of
RBCs after entering the
bloodstream.
● RBC destruction that occurs when
macrophages ingest and destroy
RBCs is termed extravascular.
● Signs of hemolysis that typically are
associated with intravascular
hemolysis (and not extravascular)
include:
○ Hemoglobinuria
○ Hemosiderinuria
○ Hemoglobinemia
● An elderly Caucasian woman is
evaluated for worsening anemia with
a decrease of approximately 0.5
mg/dL of Hb each week. The patient
is pale, and her skin and eyes are
slightly yellow. She complains of
extreme fatigue, being unable to
complete the tasks of daily living
without napping mid-morning and
mid-afternoon. She also tires with
exertion, finding it difficult to climb
even five stairs. The features in this
description which points to a
hemolytic cause of her anemia is her
yellow skin and eyen.
● Reticulocyte count test is a good
indication of accelerated
erythropoiesis,
● A 5-year-old girl was seen by her
physician several days ago and
diagnosed with pneumonia. Her
mother has brought her to the
physician again because the girl’s
urine began to darken after the first
visit and now is alarmingly dark. The
girl has no history of anemia, and
there is no family history. A CBC
shows a mild anemia,
polychromasia, and a few
schistocytes. This anemia could be
categorized as acquired,
intravascular.
● The patient has a personal and
family history of a mild hemolytic
anemia. The patient has a
consistently elevated total and
indirect serum bilirubin and elevated
urinary urobilinogen. The serum
haptoglobin is consistently
decreased, whereas reticulocytes
are elevated. The latter can be seen
as polychromasia on the patient’s
blood smear along with spherocytes
as evidence of the hemolysis.
Among these findings reported,
spherocytes on the peripheral smear
is inconsistent with a diagnosis of
intravascular hemolysis.
 ● Macrophages of the spleen liberate
bilirubin during Hb catabolism is true
about bilirubin metabolism.
● A patient is evaluated for anemia,
and the conclusion is drawn that the
anemia does not have hemolytic
component. The patient’s evaluation
is as follows:
The patient’s anemia has been
worsening over the last several
months. The Hb has been declining
with a drop of 1.5 g/dL of Hb over
about 6 weeks. Polychromasia and
anisocytosis are seen on the blood
smear, consistent with the elevated
reticulocyte count and RDW. Serum
total bilirubin and indirect fractions
are normal. Urinary urobilinogen is
also normal.
Based on this evaluation, the
hemolysis was ruled out as the
cause of the anemia because the
evidence of the increased
protoporphyrin catabolism is lacking.
● The result below is expected with
intravascular hemolysis:
○ Serum haptoglobin:
■ Decreased
○ Serum Methemalbumin:
■ Increased
○ Serum Hemopexin-Heme:
■ Increased
CHAPTER 23
Intracorpuscular Defects Leading to
Increased erythrocyte Destruction
● An outstanding abnormality of
hereditary spherocytosis noted in the
CBC is increased MCHC.
● The altered shape of the spherocyte
in HS is due to abnormal RBC
membrane protein.
● Increased osmotic fragility and
negative DAT is consistent with HS.
● RBCs in HE are abnormally shaped
and have unstable cell membranes
as a result of fragile self association
of sprectrin to spectrin.
● The blood picture for patients with
with mild common HE is
characterized by greater than 30%
elliptocytes on the blood smear and
no anemia, but patient may have a
mild compensated hemolysis.
● Laboratory tests for patients with
hereditary pyropoikillocytosis include
all of the following:
○ RBCs that show marked
thermal sensitivity at 45℃ to
46℃
○ Marked poikilocytosis with
elliptocytes, RBC fragments,
budding RBCs, spherocytes
and triangular RBCs
○ Markedly increased osmotic
fragility and autohemolysis
● Acanthocytes are found in
association with G6PD deficiency.
● The classic manifestation of G6PD
deficiency is chronic hemolytic
anemia owing to cell shape change.
● The most common defect or
deficiency in the anaerobic glycolytic
 pathway is methemoglobin ● When one alpha gene is missing
reductase. (ɑ-/ɑɑ), a patient has normal Hb.

Chapter 27 ● Hydrops fetalis is more common

Thalassemias Southeast Asia.

● The thalassemias are caused by ● The condition of Hb S-Beta

absent or defective synthesis of thalassemia has a clinical course
polypeptide chain in hemoglobin. that resembles sickle cell anemia.

● Thalassemia is more prevalent in ● Hb H inclusions in supravital stain

individuals from areas along the appear as small, multiple, irregularly
tropics because it confers selective shaped, greenish-blue bodies that
advantage against malaria. resemble golf balls.
●
● The hemolytic anemia associated
with the thalassemia is due to
imbalance of globin chain synthesis.

● Beta thalassemia minor

(heterozygous) usually has
increased Hb A2.

● The RBC morphology in beta

thalassemia would most likely
include microcytic cells,
hypochromic cells, target cells and
stippled cells.

● The major Hb present on

electrophoresis in beta thalassemia
major is Hb F.

● Heterozygous hereditary persistence

of fetal hemoglobin has 15% to 30%
of Hb F with normal RBC
morphology.

● Hb H is composed of four beta

chains.

● Hb Bart is composed of four gamma

chains.