Microcytic Hypochromic Anemia

1
Microcytic Hypochromic Anemia

• M Qari

2
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

3
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.

4
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

5
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)

6
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

7

• Definitions
• Anemia-values of hemoglobin, hematocrit or RBC
  counts which are more than 2 standard deviations
  below the mean
• HGBlt13.5 g/dL (men) lt12 (women)
• HCTlt41 (men) lt36 (women)

8
Microcytic Anemia

• MCV lt80
• Reduced iron availability
• Reduced heme synthesis
• Reduced globin production

9
Microcytic AnemiaREDUCED 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

10
Microcytic AnemiaREDUCED HEME SYNTHESIS

• Lead poisoning
• Acquired or congenital sideroblastic anemia
• Characteristic smear finding Basophylic stippling

11
Microcytic AnemiaREDUCED GLOBIN PRODUCTION

• Thalassemias
• Smear Characteristics
• Hypochromia
• Microcytosis
• Target Cells
• Tear Drops

12
Lab tests of iron deficiency of increased severity
NORMAL Fe deficiency Without anemia Fe deficiency With mild anemia Fe deficiency With severe anemia
Serum Iron 60-150 60-150 lt60 lt40
Iron Binding Capacity 300-360 300-390 350-400 gt410
Saturation 20-50 30 lt15 lt10
Hemoglobin Normal Normal 9-12 6-7
Serum Ferritin 40-200 lt20 lt10 0-10
13
Differential Diagnosis-Revisited

• Classification by Pathophysiology
• Blood Loss
• Decreased Production
• Increased Destruction

14
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)

15
Iron deficiency anemia Clinical manifestation

• Presentation of
• underlying disease 37
• anemia symptoms 63

16
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

17
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

18
Evaluation of the Patient (3)

• PHYSICAL EXAM
• Stable or Unstable?
• -ABCs
• -Vitals
• Pallor
• Jaundice
• -hemolysis
• Lymphadenopathy
• Hepatosplenomegally
• Bony Pain
• Petechiae
• Rectal-? Occult blood

19
Laboratory Evaluation

• Initial Testing
• CBC w/ differential (includes RBC indices)
• Reticulocyte count
• Peripheral blood smear

20
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
• B12/folate levels

21
Differential Diagnosis

• Classification by Pathophysiology
• Blood Loss
• Decreased Production
• Increased Destruction
• Classification by Morphology
• Normocytic
• Microcytic
• Macrocytic

22
Symptoms of anemia

• Fatigue
• Dizziness
• Headache
• Palpitation
• Dyspnea
• Lethargy
• Disturbances in menstruation
• Impaired growth in infancy

23
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

24
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

25
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

26
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

27
Laboratory findings (2)

• Iron metabolism tests
• serum iron concentration ?
• total iron-binding capacity ?
• saturation of transferrin ?
• serum ferritin levels ?
• sideroblasts ?
• serum transferrin receptors ?
• FEP ?

28
Management of iron deficiency anemia

• Correction of the iron deficiency
• orally
• intramuscularly
• intravenously
• Treatment of the underlying disease

29
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

30
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

31
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

32
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

33
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