Anemia:General

Aspects

Shi Xue

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 Definition of anemia
 Anemia is defined as a reduction in the
number of circulating erythrocytes which
cannot supply sufficient oxygen to tissues.

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 Generally, anemia is recognized in the
laboratory when a patient’s hemoglobin
(Hb)level /hematocrit(Hct) or red blood cell
(RBC)is reduced below the normal range.

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 Any decrease of the three measures of
concentration (hemoglobin, hematocrit, or
number of red cells) may be used to
establish the presence of anemia, but the
blood hemoglobin concentration is often
preferred.

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 Diagnosis criterion of anemia
 According to the diagnosis criterion of
WHO ,at sea level, anemia is:
 For adult male Hb < 130g/L

For adult female Hb<120g/L

For 6 months old to 6 years old children,
Hb<110g/L
For 6 to 14 years old children, Hb<120g/L
For pregnant women, Hb<110g/L
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 Etiology and pathogenesis
1. Impaired erythrocyte production
2. Increased red cell destruction
3. Blood loss

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 Etiology and pathogenesis
1. Impaired erythrocyte production
(1)bone marrow failure: Any condition
that is characterized by a deficiency of
hematopoietic stem cells or erythroid
precursor cells can result in anemia.

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In almost all such cases, the defect is a
more generalized bone marrow abnormality
that results in reduced production of all
lineages of bone marrow–derived cells,
particularly erythrocytes, granulocytes, and
platelets. Aplastic anemia is the prototype of
these disorders, including inherited
（ Fanconi anemia ） and acquired AA.

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(2)ineffective hematopoiesis:
IT is defined as anemia with increased
numbers of erythroid precursor cells in bone
marrow but decreased numbers of mature
circulating erythrocytes being released from
bone marrow.

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 This condition is usually caused by defects in the
maturing proerythroblasts and normoblasts in
bone marrow and results in their premature death
within the bone marrow, usually by apoptosis. The
most common causes of anemia secondary to
ineffective erythropoiesis are myelodysplasia,
megaloblastic anemia, and thalassemia.

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 (3) Inhibition of bone marrow: radiation,
drugs
 (4)bone marrow infiltration: acute leukemia,
bone metastasis of malignant tumor

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(5) Abnormal hematopoietic
microenvironment of bone marrow: stromal
cells, macromolecular substances
(6) Low levels of erythropoietin :The
prototype for impaired EPO production is
renal failure in which only low levels of EPO,
generally less than 10% of normal, are
produced .

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(7) deficiency of hematopoiesis material
Megaloblastic anemia
vitamin B12 deficiency
Folate deficiency
Iron deficiency

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2. Increased red cell destruction:

(1)Red blood cell intrinsic defect:

Hereditary: Hereditary spherocytosis

Enzyme-deficiency anemia

Thalassemia

Acquired :Paroxysmal nocturnal hemoglobinuria

(PNH)
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(2) Red blood cell extrinsic factors
immune factor: immunohemolytic anemia
non-immune factor:
hemolytic anemia result from physical,
mechanical trauma, chemical or biological
factors

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3. Blood loss
（1） acute blood loss anemia
（2） chronic blood loss anemia

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 Classification
 According to morphology
MCV(fl) MCH(pg) MCHC(%)
Macrocytic >100 >32 32-35
Normocytic 80-100 26-32 31-35
Microcytic <80 <26 31-35
Microcytic <80 <26 <31
hypochromic

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 According to etiology and pathogen
Impaired erythrocyte production

Increased red cell destruction

Blood loss

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According to severity of anemia
mild moderate severe very severe
Hb(g/L) >90 60-90 30-60 <30

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 Life span

120days

Main function
Transport O2

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Double-faced concave disk
Clinical manifestations of anemia
 The clinical signs and symptoms of
anemia will depend on how rapidly it
appears, its severity, and the tolerance
of the patient.

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 (1) Pallor: Pallor can be the most evident
sign of anemia, but many factors can affect
skin color, such as, the degree and nature of
the pigmentation, and jaundice, cyanosis,
dilation of the peripheral vessels.
 Palpebral conjunctiva, nail bed, oral mucosa,
lip
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A waxy, dead whiteness of skin maybe
suggest acute blood loss, particularly when
accompanied by cold and moist palms.
A distinctly sallow color implies chronic
anemia.

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A lemon-yellow pallor usually suggests
pernicious anemia.
Definite pallor associated with mild scleral
and cutaneous icterus suggests
hemolytic anemia.
Marked pallor associated with petechiae or
ecchymoses may imply acute leukemia.

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(2) Cardiorespiratory system:
Breathless and tachycardia. In chronic
anemia, only moderate dyspnea or
palpitation may occur, but in some patients,
congestive heart failure and angina pectoris
can be the presenting manifestation.

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Heart systolic murmurs are a common
cardiac sign associated with anemia.
Electrocardiographic changes can occur
in severe anemia and may disappear
as anemia is relieved. The most
common changes are depression of
S-T segment, and flat or inverted T
waves.

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(3) Neuromuscular system：
Headache, dizziness, vertigo, fatigue,
loss of stamina，lack of mental
concentration, drowsiness, muscular
weakness are common symptoms of
severe anemia.

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Some of these signs may be manifestations
of cerebral hypoxia. Paresthesias are
common in pernicious anemia and may be
associated with other symptoms and signs
of peripheral neuropathy.

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(4) Gastrointestinal system :
There are manifestations of the disorders
underlying the anemia (such as duodenal
ulcer or gastric carcinoma)
Other symptoms: glossitis and atrophy of
papillae of the tongue often occur in
pernicious anemia and much less often in
IDA.
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Dysphagia may occur in chronic IDA.

Non-specific symptoms :
loss of appetite, abdominal distension,
nausea, constipation, diarrhea

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(5) Genitourinary system:
Slight proteinuria, microscopic hematuria,
menstrual disorders, loss of libido

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 Diagnosis
 History :
including exposure to certain toxic agents
or drugs ; occupation; environment
pollution; the history of chronic diseases ;
menstruation; the history of pregnancy and
abortions; nutritional history; family history;
drugs intake; the courses of diagnosis and
treatment of the anemia before admission.
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 symptoms
the process ,severity and complications of
anemia
bleeding, fatigue, fever, weight loss, night
sweats and other systemic symptoms.

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 Physical examination:
Skin and mucous membrane may be
pale /sallow, scleral icterus, forceful
heartbeat, tachycardia, systolic murmur
Findings of infection, blood in the
stool, enlargement of lymph nodes ,
splenomegaly, or petechiae, sternal
tenderness.

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 Neither the pelvic nor the rectal
examination can be neglected, for tumor
or infection in these regions may also
cause anemia.

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 Laboratory examination
Routine complete blood count:
red blood cell count (hemoglobin)
red blood cell indexes(MCV,MCH,MCHC)
White blood cell count
Platelet count
Reticulocyte count

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 Hypochromic, microcytic red cells
indicate iron deficiency anemia
 Larger than normal RBCs, or
“macrocytosis,” occur in folate and
vitamin B12 deficiencies , liver disease,
some myelodysplastic disorders, and
conditions with reticulocytosis

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 Spherocytic RBCs, which lack central
pallor , appear when antibody coats the
RBC surface in congenital spherocytosis,
a heterogeneous condition with
cytoskeletal defects in RBCs.

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 Bone marrow examination
Bone marrow examination is essential to
diagnose the anemia. From bone marrow
smear and biopsy, a physician can
understand the degree of hyperplasia, the
proportion of blood cells, and if there
existed abnormal cells, and so on.

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 Other laboratory measurements :
Additional laboratory tests will be
elucidated in individual disorders.

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 USE OF THE MEDICAL HISTORY IN
DIAGNOSIS OF ANEMIAS
 History/Signs and
Symptoms
Known normal complete
blood cell count in the past
Anemia known since
childhood
Possible Etiology of
Anemia
Probably not a
hereditary disorder
Inherited/congenital
hemolytic anemia or
(less likely) bone
marrow hypoplasia
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 USE OF THE MEDICAL HISTORY IN
DIAGNOSIS OF ANEMIAS

Splenomegaly, gallstones, Chronic hemolytic

and/or jaundice anemia, liver disease
Family history of Hereditary hemolytic
splenomegaly, gallstones, anemia (RBC enzyme or
and/or jaundice membrane disorder,
thalassemia, or
hemoglobinopathy)
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 USE OF THE MEDICAL HISTORY IN
DIAGNOSIS OF ANEMIAS
Poor or unconventional diet, IDA，folate deficiency
malnutrition, or severe
alcoholism
Paresthesias, foot vitamin B12 deficiency
numbness, loss of balance,
altered mental status

Gastrectomy, surgical vitamin B12 deficiency

removal of the ileum, chronic
malabsorption disorder 43
 USE OF THE MEDICAL HISTORY IN
DIAGNOSIS OF ANEMIAS

Chronic gastritis, peptic ulcer Iron

disease, chronic use of ASA or deficiency
NSAIDs, recurrent epistaxis or rectal
bleeding, melena, menorrhagia,
metrorrhagia, hemorrhoid bleeding,
multiple pregnancies, duodenal
surgery, gastrectomy

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 USE OF THE MEDICAL HISTORY IN
DIAGNOSIS OF ANEMIAS
Dark urine Hemolytic anemia
(intravascular hemolysis)
Occupational/environmen Bone marrow
tal toxin exposure aplasia/hypoplasia, acute
(benzene, ionizing leukemia, myelodysplasia,
radiation, lead) lead poisoning
Recent onset of Bone marrow
infections, mucosal and aplasia/hypoplasia, acute
skin bleeding, easy leukemia, myelodysplasia,
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bruising, oral ulcerations myelophthisis

 Therapy
 Etiology treatment
 Supportive treatment
 Supply hematopoiesis material
 Hematopoietic growth factors
 Immunosuppressive Agents
 Allogeneic hematopoietic stem cell transplantation
 Splenectomy

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Iron Deficiency
Anemia

SHI XUE

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 Definition
 Iron deficiency anemia is the condition in
which there is an evidence of iron-store
depletion and hemoglobin synthesis is
impaired.

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 Iron metabolism
Iron supply
 Iron come from diet

 Daily diet contain approximately 10 to 15 mg

of iron, only 5%-10% will be ingested.
 Two forms of iron in diet : heme iron

and inorganic forms of iron

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 Iron absorption
Iron is absorbed in duodenum and the
proximal small intestine( upper
jejunum).
 Absorption is a carefully regulated
process that is tuned to the level of
body iron stores and the demands of
erythropoiesis.

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 It becomes more efficient as body iron
stores are depleted. Patients with certain
types of anemias, especially those with high
levels of ineffective erythropoiesis, have a
tendency to absorb excess amounts of iron.

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 Certain diets that lack iron or contain large
quantities of phytates from cereals or
tannate from tea, both of which inhibit
intestinal iron absorption, may result in
inadequate iron absorption.

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 Iron transportation
 Iron is transported through the plasma by
transferrin, a plasma glycoprotein that binds
two atoms of iron. The majority of iron-laden
transferrin molecules are destined to bind to
specific receptors on the surface of erythroid
precursors and are subsequently
internalized.

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 The iron is then released, and the
transferrin-receptor complex returns to the
cell surface where transferrin molecules are
released back to the circulation to complete
the transport cycle. The erythroid precursor
uses the delivered iron for the synthesis of
hemoglobin, storing any excess as ferritin.

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 Iron distribution and store
 Male body iron is 50mg/kg
 Female body iron is 35mg/kg

 Hemoglobin 65%,myoglobin 6%,iron stores

25% ,others in enzyme iron
 Iron is stored as ferritin or hemosiderin in
reticuloendothelial system(macrophages)

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 Iron recycle and excretion
 The bulk of the iron required for
erythropoiesis is recycled from senescent
red cells by the reticuloendothelial system
 Only 1 to 1.5 mg iron is needed from daily
diet.
 The iron is lost from desquamation of skin
and mucosal cells. Very little is lost through
bile, urine and sweat.
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 Etiology
1. Imbalance between iron intake and natural
requirements
(1) Iron malabsorption: atrophic gastritis
and extensive gastric surgery.
Chronic use of histamine 2 (H2) receptor
blockers or proton-pump inhibitors affects
the absorption of iron.

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 (2) Enhanced natural requirements
adult premenopausal female , pregnancy
and lactation, infants, children, and
adolescents

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2. Increased loss of iron:
chronic loss of blood: Gastrointestinal (GI)
blood loss is the most common type of blood
loss leading to iron deficiency .
In developed countries, the blood loss is
usually secondary to benign or neoplastic
lesions of the GI tract .

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Chronic ingestion of drugs that cause GI
mucosal damage is another frequent cause
of blood loss : the most common offending
agents are alcohol and salicylates or other
non-steroidal anti-inflammatory agents.
Other causes: helminthic infections, including
hookworm

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 Clinical Manifestations
 Symptoms of anemia:
The anemia in iron-deficient patients can be
very severe, with blood hemoglobin levels less
than 40 g/l，being encountered in some
patients. Severe iron-deficiency anemia is
associated with all of the various symptoms of
anemia, resulting from hypoxia and the body's
response to hypoxia.
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Tachycardia with palpitations and pounding
in the ears, headache, light-headedness,
tachypnea on exertion, and even angina
pectoris may all occur in patients who are
severely anemic.

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 Dysphagia
In the laryngopharynx, mucosal atrophy
may lead to web formation in the postcricoid
region, thereby giving rise to dysphagia
(Plummer-Vinson syndrome). If these
alterations are of long duration, they may
lead to pharyngeal carcinoma.

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 Pica
The craving to eat unusual substances,
such as dirt, clay, ice, laundry starch, salt,
cardboard, or hair, is a classic manifestation
of iron deficiency and is usually cured
promptly by iron therapy

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 Restless Legs
Restless legs is a common nocturnal
problem, especially in the elderly, and has
been associated with iron deficiency.

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 Hair Loss
It has been suggested that hair loss may be
a consequence of iron deficiency, and in one
study there were significantly lowered ferritin
levels in women with androgenetic alopecia.
 Koilonychia: a softening and curling of the
nails called spooning.

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 Infant and Childhood Development
Iron deficiency is associated with poor
attention span, poor response to sensory
stimuli, and retarded behavior, even in the
absence of anemia.

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Physical Findings
The physical findings in iron-deficiency
anemia include pallor, glossitis (smooth, red
tongue), stomatitis, and angular cheilitis.
Koilonychia, once a common finding, is now
encountered rarely.
Cardiovascular signs

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 Laboratory Examinations
BLOOD ROUTINE
 HGB, RBC

 MCV, MCH, MCHC

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 Laboratory Examinations
Biochemical examination
 Serum iron(SI) <8.95μmol/L(500μg/L)

 Total Iron Binding Capacity

(TIBC)>64.44 μmol/L(360μg/L)
 percent saturation of transferrin<15%

 serum ferritin level<14μg/L

 The level of red cell protoporphyrin is

elevated 70
Morphology
 Blood smear: Hypochromic microcytic
anemia can be confirmed on the
peripheral blood smear
 Bone marrow aspiration
Reticuloendothelial cell iron stores can
be estimated from the Prussian blue
stain of a marrow aspirate or a biopsy
specimen.
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 Decreased or absent
hemosiderin(extracellular iron) in the
marrow is characteristic of iron deficiency.
Hemosiderin appears in the unstained
marrow film as golden refractile granules,
but the hemosiderin content of the marrow
film is more readily and more reliably
evaluated after staining by the simple
Prussian blue method.
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 Iron granules, normally found in the
cytoplasm of 10 percent or more of
erythroblasts(intracellular iron), become
rare but may not be entirely absent.

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Center light dye area expands

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 Diagnosis
 Prelatent iron deficiency: SI is normal,
Serum ferritin and bone marrow iron store
are decreased .
 Latent iron deficiency: Percent saturation of
transferrin is decreased. The level of red cell
protoporphyrin is elevated
 IDA Hemoglobin is decreased

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 Differential diagnosis
 Thalassemia and hemoglobinpathy:
racial background and family history, the
presence of target cell, abnormal hemoglobin
pattern on electrophoresis, normal iron
stores,SI,TIBC and percent saturation of
transferrin

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 Anemia of chronic disease:
Inflammatory block in iron delivery from the
reticuloendothelial system to the erythroid
progenitors . low SI, no high TIBC, a normal to
high serum ferritin level, and, if a marrow
aspiration is performed, normal to increased
iron stores.

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 Sideroblastic anemia:
defect mitochondrial function, ringed
sideroblasts > 15%

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 Treatment
 The treatment of iron deficiency anemia is
replenishment of body iron stores.
 The underlying cause should always be
investigated before treatment is begun,
because in many cases it is a correctable
and potentially fatal GI lesion

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 Etiology therapy effective control of the
primary disease
 Oral Iron Preparations

The preferred route of iron administration is

oral.

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 Oral iron is most readily absorbed in the
absence of food, especially in the setting of
decreased stomach acid production due to
atrophic gastritis, gastric surgery, or chronic
suppression of gastric acid with an H2
antagonist or proton-pump inhibitor.

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 150 to 200 mg of elemental iron should be
provided per day.
 The major obstacle to oral iron replacement
is unacceptable gastrointestinal side effects,
chiefly epigastric discomfort or nausea,
although diarrhea or constipation also
occurs in some patients.
 Vitamin C can enhance absorption.

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 Given both the low toxicity and the low cost
of oral iron replacement, a therapeutic trial is
a complementary means for confirming a
diagnosis of iron deficiency anemia.

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 Parenteral Iron Therapy Iron can be
administered parenterally in patients who
are unable to tolerate oral iron or who suffer
from gastrointestinal malabsorption or
hemodialysis

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 The amount of iron needed can be
calculated as follows:
Total dose (mg) =(normal hemoglobin -
patient's hemoglobin, g/dL)× Body weight
(kg) ×0.24+ 500 mg

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 The most widely used parenteral iron
preparation is an iron dextran which may
be given either intramuscularly or
intravenously .
 The maximum intravenous or
intramuscular daily dose should not
exceed 100 mg of iron.

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 Usually the reticulocyte count increases 3 to
4 days after the initiation of therapy and
reaches a peak at about 7- 10 days.
Hemoglobin increases two weeks after
therapy and reaches normal value 1 to 2
months later.

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 The goal of therapy, which is to reach a
serum ferritin level of greater than 50 mg/L,
usually takes 4 to 6 months.

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 Prognosis
 In most cases, iron deficiency anemia can
be corrected rapidly by either oral or
parenteral replacement, but the long-term
prognosis ultimately depends on the therapy
of the underlying cause.
 It is critical that the patient undergo a full
evaluation to determine the underlying
cause of the iron deficiency.
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 Questions
 1.What is the definition of anemia and IDA?
 2. What is the diagnosis criterion of anemia?

 3. What is the classification of anemia

according to morphology and according to
etiology and pathogen(answer briefly)?
 4.What is the clinical manifestation of
anemia (answer briefly) and IDA?
 5.What is the principles of IDA therapy?
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