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
HGB<13.5 g/dL (men) <12 (women)
HCT<41% (men) <36 (women)

8. Microcytic Anemia MCV <80 Reduced iron availability
Reduced heme synthesis
Reduced globin production

9. 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

10. Microcytic Anemia REDUCED HEME SYNTHESIS
Lead poisoning
Acquired or congenital sideroblastic anemia
Characteristic smear finding: Basophylic stippling

11. Microcytic Anemia REDUCED 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
With mild anemia
With severe anemia
Serum Iron
60-150
<60
<40
Iron Binding Capacity
>410
Saturation
20-50 30
<15
<10
Hemoglobin
Normal
9-12
6-7
Serum Ferritin
40-200
<20
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
CBC-red cell indices-size-micro,macro, normo, color(chromasia)
WBC-leukopenia should alert to bone marrow suppression
Differential-immature forms
Retic count-high-indicates increased response to continued hemolysis or blood loss
stable anemia w/ low retic is strong evidence for deficient production of RBCs (reduced marrow response)
Smear-as above, nuceated RBCs hematologic dz(sickle, thal,hemolytic anemia), things missed by automated counters: schistocytes, RBC parasits, evidence for hemolysis

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 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 mg (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