ANEMIA BY

Hazel Carbon-Granil, RMT, MiB, MSMT

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• Inability of blood to supply tissues
with adequate oxygen for proper
metabolic function.
• Diagnosis:patient history, physical
examination, signs and symptoms,
and hematological laboratory
findings.

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• decreased levels of hemoglobin or
hematocrit (packed red cell volume) -
Abnormal hemoglobin may give appearance
of anemia (methemoglobin).
• decreased RBCs.
• Classified as moderate (Hb 7-10 g/dl) or
severe (Hb <7g/dl).
•

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• Physical signs:difficulty breathing
(dyspnea), vertigo, light-headedness,
muscle weakness, headaches, and lethargy.
Rapidly developing anemia may be
associated with hypotension and
tacchycardia.
• Two general forms:  
1. Absolute Anemia (decrease in red cell
mass) 2. Relative Anemia (increased
plasma volume gives appearance of
anemia). 
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 Considerations by Age, Sex,
and Other Factors
• Newborns less than one week old have
hemoglobin of 14-22 g/dl.
• By six months of age, hemoglobin runs
between 11 and 14 g/dl.
• 1-15 years of age:11-15 g/dl.
• Normal adult hemoglobin depends on gender:
– ♀ 12-16 g/dl
– ♂ 14-18 g/dl
• In geriatric age group, men and women:12-
16 g/dl.
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• Other factors influencing “normal”
hemoglobin include:
– Environment: elevation
– Physical Health: e.g. lung or kidney disease
– Nutritional deficiencies
– Blood loss
– Bone marrow replacement
– Chemicals / Radiation

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 CAUSES
• 3 MAJOR PATHOPHYSIOLOGICAL
CATEGORIES
1.Blood loss
2.Impaired red cell production
3.Accelerated red cell
destruction (Hemolysis)
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 RBC and Hemoglobin
Production
• In healthy individuals, about 1% of
RBCs lost daily. BM continuously
produces RBCs to equal daily loss.
– Reticulocyte count: measurement
of loss. Normal retic count is 0.5-
1.5 % of circulating RBCs.

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 RBC and Hemoglobin
Production
• Replacement requires functioning
BM, normal RBC maturation and
ability to release mature RBCs to
peripheral blood.
• Proper nutrition required (B12,
Folate). 
– requires normal hemoglobin synthesis.

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• Severe anemia (<7 Hb) organ
system failures:  Cardiac and
respiratory.
• Compensatory mechanism: 
increase in 2,3-DPG levels which
results in an increase in RBCs’
oxygen carrying capacity.

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• Erythropoietin levels (Epo)- diagnostic
tool. Anemic people usually respond by
increasing erythropoietin levels.
• Erythropoietin produced in the kidney.
– Levels of erythropoietin varies with
oxygen tension in kidney tissues (↓
Oxygen - ↑ Epo, and vice versa)

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 CLINICAL
FINDINGS
• combination of factors: patient history, physical
signs and changes in hematologic profile (CBC).
• Signs and symptoms(non-specific): fatigue,
weakness, gastrointestinal symptoms (nausea,
constipation and diarrhea), shortness of breath -
especially after exertion.
• Physical signs: pallor, low BP, a slight fever and
some edema.

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 LAB DIAGNOSIS
• CBC
• RETICULOCYTE COUNT: adult 0.5-1.5%
– Newborn 1.5-5.8%
• PERIPHERAL SMEAR EXAMINATION
• BONE MARROW EXAMINATION
• OTHER TESTS: urinalysis, Iron studies: serum
iron, TIBC, transferrin saturation and serum
ferritin
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• Anemia: diagnosed on either hemoglobin or
hematocrit values.
• Hemoglobin measurement based on
spectrophotometric absorbance readings of
cyanmethemoglobin.
• Hematocrit is packed cell volume (PCV)
determined by centrifugation:
– Normal range for adult men is 42-52%
– Normal range for women is 37-47%

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• Hb&Hct, anemia can be:mild, moderate, or severe.
• duration of onset, anemia can be:chronic or acute.
• Ratio of Hb and Hct will vary with cause of anemia
and affect the RBC indices, particularly the MCV
(Mean Corpuscular Volume).
• Microscopic examination of peripheral blood smear
is required for evaluation of anemia.  Bone marrow
aspirates and smear evaluation may also be
needed.

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 RBC INDICES
• RBC indices include:
– Mean Corpuscular Volume (MCV)
– Mean Corpuscular Hemoglobin
(MCH)
– Mean Corpuscular Hemoglobin
Concentration (MCHC)
– RBC Distribution Width (RDW)
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 MCV
• Mean cell volume
• MCV is average size of RBC
• MCV = Hct (%) x 10
RBC (x10¹²/L)
• If 80-100 fL, normal range, RBCs considered
normocytic
• If < 80 fL are microcytic, If > 100 fL are
macrocytic
• Not reliable when have marked anisocytosis

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 MCH
• MCH is average weight of
hemoglobin per RBC.
• MCH = Hgb (g/dL) x 10
RBC (x10¹²/L)
- Adult reference interval: 26-32 pg
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 MCHC
• MCHC is average hemoglobin concentration
per RBC
• MCHC = Hgb (g/dL) x 100
Hct (%)
- Adult reference interval: 32-36 g/dL
• If MCHC is normal, cell described as
normochromic
• If MCHC is less than normal, cell described as
hypochromic

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 RDW
• Most automated instruments now provide
an RBC Distribution Width (RDW)
• An index of RBC size variation
• May be used to quantitate the amount of
anisocytosis on peripheral blood smear
• Normal range is 11.5% to 14.5% for both
men and women

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 DISORDERS
OF IRON AND
HEME
METABOLISM
ANEMIA 1

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 IRON DEFICIENCY
ANEMIA
Inadequate intake of iron & of food.
High intake of inhibitors of iron absorption.
Hookworm infestation.
Blood loss (heavy menses & use of aspirin
& NSAID).
High fertility rate in womem.
Low iron stores in newborns.

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 DIETARY IRON
2 types of iron in the diet; heme iron and
non-heme iron
Heme iron is present in Hb containing
animal food like meat, liver & spleen
Non-heme iron is obtained from cereals,
vegetables & beans
Milk is a poor source of iron, hence breast-
fed babies need iron supplements

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 IRON ABSORPTION
Heme iron is not affected by ingestion of
other food items.
It has constant absorption rate of 20-30%
which is little affected by the iron balance
of the subject.
The heme molecule is absorbed intact and
the iron is released in the mucosal cells.

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The absorption of non-heme iron varies greatly
from 2% to 100% because it is strongly influenced
by:

The iron status of the body

The solubility of iron salts
Integrity of gut mucosa
Presence of absorption inhibitors or facilitators

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 INHIBITORS OF IRON
ABSORPTION
Food with polyphenol compounds
Cereals like sorghum & oats
Vegetables such as spinach and spices
Beverages like tea, coffee, cocoa and
wine.
A single cup of tea taken with meal
reduces iron absorption by up to 11%.

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 OTHER INHIBITORS
Food containing phytic acid i.e.
Bran, cereals like wheat, rice,
maize & barely.
Legumes like soya beans, black
beans & peas.
Cow’s milk due to its high
calcium & casein contents.
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 INHIBITION-HOW?
The dietary phenols & phytic acids
compounds bind with iron decreasing
free iron in the gut & forming
complexes that are not absorbed.
Cereal milling to remove bran reduces
its phytic acid content by 50%.
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 Promoters of Iron Absorption
 Foods containing ascorbic acid like citrus fruits,
broccoli & other dark green vegetables
 ascorbic acid reduces iron from ferric to ferrous forms,
which increases its absorption.
 Foods containing muscle protein enhance iron
absorption due to the effect of cysteine containing
peptides released from partially digested meat.
 reduces ferric to ferrous salts and form soluble iron
complexes.

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 IRON ABSORPTION
Some fruits inhibit the absorption of
iron although they are rich in ascorbic
acid because of their high phenol
content e.g strawberry banana and
melon.
Food fermentation aids iron absorption
by reducing the phytate content of diet
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 IRON TRANSPORT
Transferrin is the major protein responsible
for transporting iron in the body.
Transferrin receptors, located in almost all
cells of the body, can bind two molecules
of transferrin.
Both transferrin concentration & transferrin
receptors are important in assessing iron
status.

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 STORAGE OF IRON
Tissues with higher requirement for iron
( bone marrow, liver & placenta) contain more
transferrin receptors.
Once in tissues, iron is stored as ferritin &
hemosiderin compounds, which are present in the
liver, RE cells & bone marrow.
The amount of iron in the storage compartment
depends on iron balance (positive or negative).
Ferritin level reflects amount of stored iron in the
body & is important in assessing ID.

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 ROLE OF IRON IN THE
BODY
Iron have several vital functions
Carrier of oxygen from lung to tissues
Transport of electrons within cells
Co-factor of essential enzymatic reactions:
Neurotransmission
Synthesis of steroid hormones
Synthesis of bile salts
Detoxification processes in the liver

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 CAUSES FOR
•
DEVELOPMENT
Decreased iron intake
of IDA
• Increasing demand for iron and the
reduction of the deposit (or the frequency
of multiple pregnancies, prematurity,
lactation periods of rapid growth, sports)
• Chronic blood loss (nasal bleeding, bleeding
from GIT, menorrhagia, renal hemorrhage,
idiopathic lung hemosiderosis)
• Reduction of iron absorption
(malabsorption, chronic inflammatory
diseases GIT, gastrectomy).
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 Developmental Stages of Iron
Deficiency Anemia (WHO, 1977)
• Pre-latent (exhaustion of tissue reserve of
iron; index of the blood within the standard;
there are no clinical manifestations)
• Latent (deficit of iron in the tissue and the
decrease of its reservoir transport; index of
the blood within the standard; clinical picture
is caused by the sideropenic syndrome)
• Iron Deficiency Anemia (deviation from the
standard index of the blood; the clinical
manifestations in the form of sideropenic
syndrome and general anemic symptoms)
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 LAB DIAGNOSIS-
IDA
 A decrease MCV - less than 75
 Increase RDW
 A decrease MCHC - less than 30.
 Morphology of the erythrocytes - hypochromic,
anisocytosis and poikilocytosis
 Biochemical - decrease level of serum ferritin
 Decrease level of serum iron
 Increase Total Iron Binding Capacity (TIBC)
 Increase level of serum transferrin
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 ANEMIA OF
CHRONIC
INFLAMMATION
rheumatoid arthritis
Tuberculosis
HIV
Cancer
Kidney disease
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• ACI is easily confused with iron-
deficiency anemia because in both
forms of anemia levels of iron
circulating in the blood are low.
• Iron in the body is found both
circulating in the blood and stored in
body tissues. Circulating iron is
necessary for red blood cell
production.
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• Low blood iron levels occur in iron-deficiency anemia
because levels of the iron stored in the body’s tissues
are depleted.
• In ACI, however, iron stores are normal or high. Low
blood iron levels occur despite normal iron stores,
because inflammatory and chronic diseases interfere
with the body’s ability to use stored iron and absorb
iron from the diet.
• ACI is the second most common form of anemia, after
iron-deficiency anemia.

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 ETIOLOGY
•Impaired ferrokinetics:
– HEPCIDIN: hormone produced by
hepatocytes, regulates absorption of iron in
the intestines and release iron from the
macrophages.
• Acute phase reactant: levels increase during
inflammation, decrease in iron absorption.

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 • Although plenty iron in the body, it is unavailable
to developing RBCs because it is sequestered in
the macrophages and hepatocytes.
– LACTOFERRIN: iron-binding protein in neutrophils
• Released into the plasma during inflammation
and infection. It scavenges available iron at the
expense of transferrin – bound to macrophages
and liver cells that salvages the iron.

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 – FERRITIN: increased level in the
plasma also bind some iron.
• RESULT: although iron is present in
abundance in BM macrophages, its
release to developing erythrocytes is
slowed.

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 SYMPTOMS
• develops slowly and, because it is usually mild,
may cause few or no symptoms.
• masked by the symptoms of the underlying
disease. Sometimes, ACI can cause or contribute
to:
– Fatigue, weakness, pale skin
– a fast heartbeat
– shortness of breath
– exercise intolerance

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 LAB DIAGNOSIS-
ACI
• CBC: Hb 9-11 g/dL without
reticulocytosis
– Normocytic, normochromic
– Leukocytosis, thrombocytosis or
both
• Iron studies:low serum iron and TIBC
– Serum ferritin increased/Normal
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• The ferritin level indicates the
amount of iron stored in the body. A
ferritin score below 200 nanograms
per liter is a sign that a person may
have an IDA.

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• The transferrin saturation (TSAT) is a
score that indicates how much iron is
available, or circulating, to make RBCs.
A TSAT score below 20 percent is
another sign of IDA.
• A lab result that shows low iron levels
in the blood yet normal measures of
iron stores in the body is a hallmark of
ACI.

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RECAP: Iron:Hb, myoglobin, enzymes & body cells.
– 2/3 or more:normoblasts and erythrocytes:1mg of iron/mL of
red cells
– Storage iron(macrophages of RES): ferritin and hemosiderin
(Henry’s.page 558)
– IDA:iron loss exceeds iron intake;microcytic, hypochromic
anemia
• Storage iron decreases, plasma ferritin decreases, TIBC
(transferrin) increases.
– ACI:increased levels of hepcidin; decreased iron absorption,
decreased iron release, impaired EPO production.
• Decreased serum iron, TIBC, dec/N transferrin saturation,
N/inc Ferritin.

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SIDEROBLASTIC
ANEMIA

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• heterogeneous group of disorders with two
common features: ring sideroblasts in the
bone marrow (abnormal normoblasts with
excessive accumulation of iron in the
mitochondria) and impaired heme
biosynthesis. *acquired and hereditary
• mitochondrion
– disturbed mitochondrial metabolism(heme synthesis),
enzyme defects:center of all sideroblastic anemias.

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Heme biosynthesis begins in the mitochondrion with the formation of 5-
aminolevulinic acid. This molecule moves to the cytosol where a
number of additional enzymatic transformations produce
coproporphyrinogin III. The latter enters the mitochondrion where a
final enzymatic conversion produces protophorphyrin IX. Ferrochelase
inserts iron into the protophorin IX ring to produce HEME

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 LEAD POISONING
• Lead interferes with porphyrin synthesis:
– Conversion of ALA to porphobilinogen,
results to accumulation of ALA.
– Incorporation of iron into protoprophyrin IX
by ferrochelatase (heme synthetase),
results to accumulation of iron and
protoporphyrin.
• Children with lead intoxication more
commonly develop SA than do adults.
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PORPHYRIAS

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• HEME precursors:
Delta-aminolevulinic acid
porphobilinogen
Uroporphyrinogen
Coproporphyrinogen
Protoporphyrin
HEME+globin
PORPHYRIAS;excessive formation of porphyrins occurs if any enzymatic step in heme
synthesis is blocked.
-red or port wine colored urine
-DELTA-POR=neuropsychiatric symptoms/acute intermittent porphyria
-UR,COP,PROTO=cutaneous symptom

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 PORPHYRIAS
• Impaired production of protoporphyrin and
HEME (hereditary type)
• Porphyrias are classified in two ways, by
symptoms and by pathophysiology.
– Symptomatically, acute porphyrias
primarily present with nervous system
involvement, often with severe abdominal
pain, vomiting, neuropathy and mental
disturbances.
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 PORPHYRIAS
• Cutaneous porphyrias present with skin
manifestations often after exposure to sun due to the
accumulation of excess porphyrins near the surface of
the skin.
• Physiologically;
• HEPATIC or ERYHTHROPOIETIC based on the
sites of accumulation of heme precursors,
either in the liver or bone marrow and red
blood cells.
• Rodak, 5th ed. Page 307(table)

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 Type of
Deficient enzyme Associated porphyria
porphyria
δ-aminolevulinate (ALA) X-linked sideroblastic Erythropoieti
synthase anemia (XLSA) c
δ-aminolevulinate dehydratase Doss porphyria/ALA
Hepatic
(ALAD) dehydratase deficiency
hydroxymethylbilane (HMB) acute intermittent
Hepatic
synthase (or PBG deaminase) porphyria (AIP)
uroporphyrinogen (URO) Congenital erythropoietic Erythropoieti
synthase porphyria (CEP) c
uroporphyrinogen (URO) Porphyria cutanea tarda
Hepatic
decarboxylase (PCT)
coproporphyrinogen (COPRO) Hereditary coproporphyria
Hepatic
oxidase (HCP)
protoporphyrinogen (PROTO)
Variegate porphyria (VP) Mixed
oxidase
Erythropoietic Erythropoieti
Ferrochelatase
protoporphyria (EPP) c
Transient erythroporphyria
of infancy
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 IRON
OVERLOAD

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• iron overload indicates accumulation of iron in the
body from any cause; iron acquisition exceeds loss
• Primary: hereditary hemochromatosis
• Secondary: chronic anemias and their treatments
• Body stores excess iron in the form of ferritin and
hemosiderin within cells. 1mg/day; storage system
is overwhelmed-parenchymal cells are damaged in
organs.

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• Repeated transfusions(SSA and Thal):receive
20 units of red blood cell transfusions.
– iron overload as a result of multiple transfusions
• MDS patients with sideroblastic anemia - a
result of excessive absorption of iron from
food.
– excess iron is building up in the body.
• excess iron can damage tissues.

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HEMOCHROMATOSIS
• Mutation gene(HFE)-iron metabolism
• Hemochromatosis (iron storage disease)
-the body absorbs too much iron.
• causes extra iron to gradually build up
in the body’s tissues and organs.
– If this iron buildup is not treated, it can
damage the body’s organs.

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• Result of mutations affecting the proteins of
iron metabolism.
• Free iron (damage organ) becomes
available in cells when Ferritin and
hemosiderin becomes saturated.
• The HFE gene - located on chromosome 6;
the majority of hereditary hemochromatosis
patients have mutations in this HFE gene.
• Rodak 5th ed. Page 308 (table:Mutations)

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 LAB DIAGNOSIS
• Transferrin saturation and Ferritin
level:common screening test –
increased.
• Normal values for serum ferritin are
usually in the range of 15–400
ng/mL for men and 10–106 ng/mL
for women.

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 LAB DIAGNOSIS
– A low serum ferritin level means reduced
iron stores.
– Lower than normal levels of ferritin-IDA
– higher than normal levels may indicate
hemolytic anemia, megaloblastic anemia, or
iron overload
– Serum ferritin levels greater than 1000 –
2500 ng/mL indicate iron overload

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 END…
ASSIGNMENT50/50
READ, AND Make a TABLE of:
ANALYZE : 1.Normal values:
Case study of Serum Iron, TIBC,
Chapter 20 Serum Ferritin,
%Transferrin
Rodak’s
saturation.
HEMATOLOGY
Clinical Principles 2.Iron studies:IDA,
and Applications 5thheyzgran ACI, SA and LP 67