Microcytic Hypochromic Anemia

• M Qari
Differential diagnosis of microcytic hypochromic
anemia

• Iron deficiency and iron deficiency anemia

• The anemia of chronic disorders
• Sideroblastic anemias
• Thalassemia Major
• Lead Poisoning
• Hereditary pyropoikilocytosis
Iron metabolism

• Most body iron is present in haemoglobin in circulating red

cells
• The macrophages of the reticuloendotelial system store iron
released from haemoglobin as ferritin and haemosiderin
• They release iron to plasma, where it attaches to transferrin
which takes it to tissues with transferrin receptors – especially
the bone marrow – where the iron is incorporated by erythroid
cells into haemoglobin
• There is a small loss of iron each day in urine, faeces, skin and
nails and in menstruating females as blood (1-2 mg daily) is
replaced by iron absorbed from the diet.
 RBC-The important players (2)
• Iron
– key element in the production of hemoglobin
– absorption is poor
• Transferrin
– iron transporter
• Ferritin
– iron binder, measure of iron stores, *also acute phase
reactant*
Stages in the development of iron deficiency
• Prelatent
– reduction in iron stores without reduced serum iron levels
• Hb (N), MCV (N), iron absorption (), transferin saturation (N),
serum ferritin (), marrow iron ()
• Latent
– iron stores are exhausted, but the blood haemoglobin level remains
normal
• Hb (N), MCV (N), TIBC (), serum ferritin (), transferin
saturation (), marrow iron (absent)
• Iron deficiency anemia
– blood haemoglobin concentration falls below the lower limit of normal
• Hb (), MCV (), TIBC (), serum ferritin (), transferin saturation
(), marrow iron (absent)
Iron deficiency and iron deficiency anemia
• The characteristic sequence of events ensues when the
total body iron level begins to fall:
1. decreases the iron stores in the macrophages of the
liver, spleen and bone marrow
2. increases the amount of free erythrocyte
protoporphiryn (FEP)
3. begins the production of microcytic erythrocytes
4. decreases the blood haemoglobin concentration
• Definitions
• Anemia-values of hemoglobin, hematocrit or
RBC counts which are more than 2 standard
deviations below the mean
– HGB<13.5 g/dL (men) <12 (women)
– HCT<41% (men) <36 (women)
 Microcytic Anemia
• MCV <80
• Reduced iron availability
• Reduced heme synthesis
• Reduced globin
production
 Microcytic Anemia
REDUCED IRON AVAILABILTY
• Iron Deficiency
– Deficient Diet/Absorption
– Increased Requirements
– Blood Loss
– Iron Sequestration
• Anemia of Chronic Disease
– Low serum iron, low TIBC, normal serum ferritin
– MANY!!
• Chronic infection, inflammation, cancer, liver disease
 Microcytic Anemia
REDUCED HEME SYNTHESIS
• Lead poisoning
• Acquired or congenital
sideroblastic anemia
• Characteristic smear
finding: Basophylic
stippling
 Microcytic Anemia
REDUCED GLOBIN PRODUCTION
• Thalassemias
• Smear Characteristics
– Hypochromia
– Microcytosis
– Target Cells
– Tear Drops
 Lab tests of iron deficiency of
increased severity
NORMAL Fe deficiency Fe deficiency Fe deficiency
Without anemia With mild anemia With severe anemia

Serum Iron 60-150 60-150 <60 <40

Iron Binding 300-360 300-390 350-400 >410

Capacity
Saturation 20-50 30 <15 <10

Hemoglobin Normal Normal 9-12 6-7

Serum Ferritin 40-200 <20 <10 0-10

 Differential Diagnosis-Revisited
• Classification by Pathophysiology
– Blood Loss
– Decreased Production
– Increased Destruction
Iron deficiency anemia
Definition and etiologic factors
• The end result of a long period of negative iron balance
– decreased iron intake
• inadequate diet, impaired absorption, gastric surgery, celiac disease
– increased iron loss
• gastrointestinal bleeding (haemorrhoids, salicylate ingestion, peptic
ulcer, neoplasm, ulcerative colitis)
• excessive menstrual flow, blood donation, disorders of hemostasis
– increased physiologic requirements for iron
• infancy, pregnancy, lactation
– cause unknown (idiopathic hypochromic anemia)
Iron deficiency anemia
Clinical manifestation
• Presentation of

– underlying disease 37%

– anemia symptoms 63%

 Evaluation of the Patient
• HISTORY
– Is the patient bleeding?
• Actively? In past?
– Is there evidence for increased RBC destruction?
– Is the bone marrow suppressed?
– Is the patient nutritionally deficient? Pica?
– PMH including medication review, toxin exposure
 Evaluation of the Patient (2)
REVIW OF SYMPTOMS
• Decreased oxygen delivery to tissues
– Exertional dyspnea
– Dyspnea at rest
– Fatigue
– Signs and symptoms of hyperdynamic state
• Bounding pulses
• Palpitations
– Life threatening: heart failure, angina, myocardial infarction
• Hypovolemia
– Fatiguablitiy, postural dizziness, lethargy, hypotension, shock
and death
 Evaluation of the Patient (3)
PHYSICAL EXAM
•Stable or Unstable?
-ABCs
-Vitals
•Pallor
•Jaundice
-hemolysis
•Lymphadenopathy
•Hepatosplenomegally
•Bony Pain
•Petechiae
•Rectal-? Occult blood
 Laboratory Evaluation
• Initial Testing
– CBC w/ differential (includes RBC indices)
– Reticulocyte count
– Peripheral blood smear
 Laboratory Evaluation (2)
• Bleeding
– Serial HCT or HGB
• Iron Deficiency
– Iron Studies
• Hemolysis
– Serum LDH, indirect bilirubin, haptoglobin, coombs,
coagulation studies
• Bone Marrow Examination
• Others-directed by clinical indication
– hemoglobin electrophoresis
 Differential Diagnosis
• Classification by Pathophysiology
– Blood Loss
– Decreased Production
– Increased Destruction
• Classification by Morphology
– Normocytic
– Microcytic
– Macrocytic
Symptoms of anemia

• Fatigue
• Dizziness
• Headache
• Palpitation
• Dyspnea
• Lethargy
• Disturbances in menstruation
• Impaired growth in infancy
Symptoms of iron deficiency

• Irritability
• Poor attention span
• Lack interest in surroundings
• Poor work performance
• Behavioural disturbances
• Pica
• Defective structure and function of epithelial tissue
– especially affected are the hair, the skin, the nails, the tongue, the
mouth, the hypopharynx and the stomach
• Increased frequency of infection
Pica

• The habitual ingestion of unusual substances

– earth, clay (geophagia)
– laundry starch (amylophagia)
– ice (pagophagia)

• Usually is a manifestation of iron deficiency and is

relieved when the deficiency is treated
Abnormalities in physical examination
• Pallor of skin, lips, nail beds and conjunctival mucosa
• Nails - flattened, fragile, brittle, koilonychia, spoon-shaped
• Tongue and mouth
– glossitis, angular cheliosis, stomatitis
– dysphagia (Peterson-Kelly or Plummer-Vinson syndrome
(carcinoma in situ)
• Stomach
– atrophic gastritis, (reduction in gastric secretion, malabsorbtion)

• The cause of these changes in iron deficiency is uncertain, but

may be related to the iron requirement of many enzymes present
in epithelial and other cells
Laboratory findings (1)
• Blood tests
– erythrocytes
• hemoglobin level 
• the volume of packed red cells (VPRC) 
• RBC 
• MCV and MCH 
• anisocytosis
• poikilocytosis
• hypochromia
– leukocytes
• normal
– platelets
• usually thrombocytosis
Laboratory findings (2)

• Iron metabolism tests

– serum iron concentration 
– total iron-binding capacity 
– saturation of transferrin 
– serum ferritin levels 
– sideroblasts 
– serum transferrin receptors 
– FEP 
Management of iron deficiency anemia

• Correction of the iron deficiency

– orally
– intramuscularly
– intravenously

• Treatment of the underlying disease

 Oral iron therapy
• The optimal daily dose - 200 mg of elemental iron
–Ferrous
• Gluconate 5 tablets/day
• Fumarate 3 tablets/day
• sulphate 3 tablets/day
– iron is absorbed more completely when the stomach is empty
– it is necessary to continue treatment for 3 - 6 months after the anemia is relived
– iron absorption
» is enhanced: vitC, meat, orange juice, fish
» is inhibited: cereals, tea, milk
• side effects
– heartburn, nausea, abdominal cramps, diarrhoea
Failure of oral iron therapy

• Incorrect diagnosis
• Complicating illness
• Failure of the patient to take prescribed medication
• Inadequate prescription (dose or form)
• Continuing iron loss in excess of intake
• Malabsorbtion of iron
Parenteral iron therapy (1)

• Is indicated when the patient

– demonstrated intolerance to oral iron
– loses iron (blood) at a rate to rapid for the oral intake
– has a disorder of gastrointestinal tract
– is unable to absorb iron from gastrointestinal tract
Parenteral iron therapy (2)

• Preparations and administration

– iron - dextran complex (50mg iron /ml)
• intramuscularly or intravenously
• necessary is the test for hypersensitivity
• the maximal recommended daily dose - 100mg (2ml)
– total dose is calculated from the amount of iron needed to
restore the haemoglobin deficit and to replenish stores
• iron to be injected (mg) = (15-pts Hb/g%/) x body weight
(kg) x 3
Parenteral iron therapy (3)

• Side effects
• local: pain at the injection site, discoloration of the skin,
lymph nodes become tender for several weeks, pain in the
vein injected, flushing, metallic taste
• systemic:
– immediate: hypotension, headache, malaise, urticaria,
nausea, anphylactoid reactions
– delayed: lymphadenophaty, myalgia, artralgia, fever