1. Anemia

2. Introduction
• Not a single disease
• Results from a number of different pathologies
• Defined as a reduction from the normal quantity of
Hb in blood
• Who defines anemia as Hb levels less than 13 g/dl for
males and less than 12 g/dl for females
• Low Hb levels results in decreased oxygen carrying
capacity of blood

3. Epidemiology
• Most common condition resulting in significant
morbidity and mortality
• Worldwide: Over 50% of pregnant women and 40 %
of infants are anemic

4. Aetiology
Two different mechanisms:
1. Reduced Hb synthesis (due to lack of nutrient
or bone marrow failure)
Reduced proliferation of precursors or
defective maturation of precursors or both

5. Aetiology (contd…)
• Increased Hb loss due to haemorrhage (red cell
loss) or hemolysis (red cell destruction)
(More than one cause can be found in a patient)

6. Normal erythropoiesis
Pluripotent stem cell
Erythroid burst forming unit
Erythroid colony forming unit Within BM
Erythroblast
Reticulocyte
Mature red cell
Peripheral
blood

7. Normal erythropoiesis (contd…)
• Erythropoietin production si impaired n
condictions such as RA, cancer and Sickle cell
anemia
• Each day about 2 *1011 erythrocytes enter
the circulation
• Normally survive for 120 days

8. Normal erythropoiesis (contd…)
• Destroyed by reticuloendothelial system
found in spleen and BM
• Iron is removed from haem component of Hb
and transported back into bone marrow for
reuse

9. Normal erythropoiesis (contd…)
• Pyrole ring from globin is excreted as
conjugated bilirubin by the liver and the
polypeptide portion enters the body’s protein
pool

10. Clinical manifestations
• Mildest form: tiredness and lethargy, reduced
mental performance
• Non-specific signs and symptoms associated with
anemia:
Tiredness, Pallor, Fainting, Exertional dyspnea,
Tachycardia, Palpitations, Worsening angina,
Worsening cardiac failure, Exacerbation of
intermittent claudication

11. Investigations
• No place for blind treatment
• Anemia is a consequence of reduced concentration of Hb in
each red cell and/or reduced number of red cells in peripheral
circulation
• Imp parameter: Hb concentration of blood, including its size ,
shape and color, MCV to determine type of anemia
• Bone marrow examination

12. Iron deficiency anemia
• Epidemiology: 20% of world’s population
• Cause: diet deficient in iron, parasitic infestations
and multiple pregnancies
• Aetiology: Blood loss, GI bleeding (most likely),
Haemorrhoids, nosebleeds or postpartum
haemorrhage

13. Iron deficiency anemia
Causes of Iron deficiency anemia
• Inadequate iron absorption
Dietary deficiency
Malabsorption
• Increased physiological demand
• Loss through bleeding

14. Pathophysiology
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Elimination not controlled physiologically
Homeostasis maintained by controlling iron absorption
Absorption inefficient
Iron bound to haem is better absorbed than iron
found in vegetables
• Phosphates and phytates leads to formation of
unabsorbable complex, while ascorbic acid increases
iron absoprtiopn

15. Pathophysiology (contd…)
• Anemia a result of mismatch between body’s
iron requirement and iron absoprtion
• Fortified milk given to children up to the age of
18 months increases Hb levels and improve
performance
• Iron malabsoprtion occurs in patients with
coleliac disease and in 50% patients following
gastrectomy

16. Pathophysiology (contd…)
• During pregnancy: dilutional anemia
• Some of the increased demand is met by
stopping menstruation
Whatever the cause might
be
inadequate iron
absorption leads
to anemia

17. Clinical manifestations
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Pale skin and mucous membrane
Painless glossitis
Angular stomatitis
Koilonychia
Dysphagia
Pica
Atrophic gastritis

18. Investigations
• Serum iron, Total iron binding capacity (TIBC)
and serum ferritin
• Aim: To correct anemia and replenish iron
stores
Important to resolve the
underlying cause as far
as possible

19. Treatment
• Folic acid use during pregnancy
• Prophylaxis in menorrhagia, after partial
gastrectomy and in some low birth weight
infants
• Continue for 6 months to both correct anemia
and replenish body stores
• Standard treatment: 200 mg three times a day

20. Treatment (contd…)
• It takes 1 to 2 weeks for Hb level to rise to 1
g/dl
• N and abdominal pain occurs in some patients
• Alternative salts of iron are tried
• Absorption is 15% of intake during the first 2-3
weks but falls off to an average of 5%
thereafter
• Modified release oral preparations also
available

21. Treatment (contd…)
• There is little place for parenteral iron
• In renal patients, a regular weeks dose is often
given and patients’ serum ferritin monitored
to check for iron overload

22. MEGALOBLASTIC ANEMIA
• They are macrocytic anemia (raised MCV)
• Abnormality in the maturation of
haemopoietic cells in the bone marrow
• Two causes: Folate deficiency and Vit. B12
deficiency anemia
• Pernicious anemia is a specific disease caused
by malabsorption of Vit B12

23. Aetiology
Folate deficiency anemia
• Readily available in normal diet (Fruit, green
vegetables and yeast)
• Folate deficiency either due to folic acid
deficiency anemia or increased folate
utilization

24. Aetiology (contd…)
Vitamin B12 deficiency anemia
• Inadequate intake or malabsorption (dueto
removal of distal ileum)
• Dietary source: Food of animal origin
• Daily requirements: 1-2 micrograms

25. Pathophysiology
• Common: inhibition of DNA synthesis in
maturing cells

26. Folate deficiency anemia
Dietary folate
Gut
Folate monoglutamate
Methyltetrahydrofolate monoglutamate
Tetrahydrofolate monoglutamate
Bone
Tetrahydrofolate polyglutamate
marrow
Folate co-enzymes
Dihydrofolate
Polyglutamate

27. Pathophysiology of Vit. B12 deficiency anemia
• Absorption occurs by an active process
• Enzyme in the stomach release Vit. B12 from protein complexes
• One molecule of Vit. B12 combine with one molecule of
glycoprotein (called intrinsic factor)
• There are specific receptors in the distal ileum for intrinsic
factor-Vit B12 complex
• Vit B12 enters the ileal cell and is then transported through the
blood attached to transport proteins
• A total gastrectomy always leads to Vit. B12 deficiency
• Onset of anemia is usually delayed

28. Pathophysiology of pernicious anemia
• Autoimmune in origin
• Patients typically have a gastric atrophy and no or
virtually no intrinsic factor secretion
• Two different intrinsic factor antibodies have been
produced in serum of patients with pernicious
anemia
• Gastric parietal antibodies found (in 90% patients)

29. Clinical manifestations
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Glossitis
Angular stomatitis
Altered bowel habit
Anorexia
Mild jaundice
Insiduous onset
Sterility
Bilateral peripheral neuropathy
Melanin skin pigmentation
Fever

30. Investigations
Folic acid deficiency anemia
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Symptomless initially
Large oval red cells
Anisocytosis and poikilocytosis
Thrombocytopenia

31. Investigations (contd…)
Vit B12 deficiency anemia
• Serum Vit B12 level
• Serum folate level
• Measuring absorption of Vit. B12 (by Schilling
test)
• Parietal cell antibodies (not accurately
diagnostic)

32. Treatment
• Necessary to establish whether the patient
with megaloblastic anemia has Vit. B12
deficiency or folic acid deficiency or both

33. Treatment of folate deficiency anemia
• Replacement therapy
• Duration of treatment depends on cause
• Changes in dietary habit or removal of any
precipitating factor
• Normal daily requirement approx. 100 micrograms
per day
• Dose: 5-15 mg per day for 4 months
• Parenteral folic acid treatment not normally required

34. Treatment of folate deficiency anemia
during pregnancy
• Folate requirement increases in pregnancy
and is higher in twin pregnancies
• Prophylaxis with folate ( 350-500 micrograms)
frequently given during pregnancy

35. Treatment of Vit. B12 deficiency anemia
• Require life long replacement therapy
• Transfusion not normally given
• If emergency transfusion deemed necessary, packed cells may
be given
• Diuretics also given
• Definite diagnosis should be made before starting treatment
• Std. treatment: Hydroxocobalamin 1 mg IM repeated five
times at 3 day intervals to replenish body stores, followed by
maintenance dose, usually 1 mg IM every 3 months.

36. Sideroblastic anemias
• Group of conditions diagnosed by finding ring
siderobalst in the BM
• Both hereditary and acquired forms present

37. Aetiology
• In hereditary forms, there is X chromosome
linked pattern of inheritance
• Both autosomal dominant and autosomal
recessive families present
• Defect: Reduced activity of the enzyme 5aminolevulinate synthase (ALAS)

38. Pathophysiology
• Examination of BM shows number of
erythroblasts that have iron granules
surrounding the cell nucleus (known ad ring
sideroblast)
• Low levels of ALAS in hereditary forms
• Drugs and toxins: Alcohol, Isoniazid in slow
acetylators, Dose of Chloramphenicol over 2 g

39. Clinical manifestations
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Develop on infancy or childhood
Severe or mild anemia
Splenomegaly
Idiopathic forms tends to develop insiduously
(middle age or later)
• Many becoem asymptomatidc for long
periods

40. Investigations
• In heriditary fomrs: red cells in peripheral blood are
hypochromic and microcytic
• Increased iron stores in BM
• Serum iron and ferritin high
• In acquired forms: Peripheral blood has hypochromic
cells which may be either normocytic or macrocytic
• Common finding: Presence of sideroblast in BM

41. Treatment
• For hereditary forms: 200 mg daily Pyridoxine
• Frequent blood transfusion required in
unresponsive patients
• Desferrioxamine given i.v or s.c
• Oral Vit. C

42. Hemolytic anemias
• Reduced life span of erythrocytes
• Imbalance between rate of destruction and
rate of production
• Presence of both genetic and acquired
disorders

43. Aetiology of Sickle cell anemia
• They have a different form of Hb (Hb S)
• Patients with homozygous Hb S develop many
problems including anemia
• Sickle cell trait is usually asymptomatic
• The offspring from a father with a trait and a mother
with a trait has a 1 in 4 chance of having sickle cell
disease
•

44. Aetiology of Thalassaemias
• No alpha chain production or reduced
production of a chain
• Heterozygotes are symptomless

45. Aetiology of G6PD deficiency
• Large variants of G6PDdeficiency
• It is an enzyme involved in the production of
reduced glutathione

46. Pathophysiology of Sickle cell disease
• Membrane of red cells containing Hb S is
damaged (lead to IC dehydration)
• Polymerization of Hb S occurs when the
patients blood is deoxygenated
• These two processes lead to crescent-shaped
cells (known sickle cell)

47. Pathophysiology of Sickle cell disease
(contd…)
• Sickle cells are less flexible than normal cells
• This leads to local tissue hypoxia
• Anemia results from an increased red cell
destruction

48. Pathophysiology of Thalassemia
• Reduced or absent production of globin beta chain
• Leads to relative excess of alpha chain, when
unpaired become unstable and precipitate in red cell
precursors
• Ineffective erythropoiesis
• In alpha thalassemia, deficiency of alpha chain leads
to an excess of beta or gamma chains

49. Pathophysiology of Thalassemia (contd…)
• Erythropoiesis is less affected but Hb
produced is unstable when the cells are in
circulation and precipitate as the cells grow
older

50. Pathophysiology of G6PD deficiency
• Essential for the production of reduced form
of NADPF in RBC
• NADPH is needed to keep gluthathione in
reduced form
• Glutathione helps RBC deal with oxidative
stress
• In G6PD deficiency Hb becomes oxidised and
Heinz bodies are form

51. Clinical manifestations
• Malaise
• Fever
Abdominal pain
• Dark urine
• Jaundice

52. Clinical manifestations of Sickle cell anemia
• Chronic anemia, arthralgia, fatigue,
splenomegaly. Crisis precipitated by infection,
fever. Dehydration, hypoxia or acidosis.
Severe pain is a common feature.

53. Clinical manifestations of thalassemia
• Causes Erythropoietin production to increase
andresulst in expansion of BM
• Bone deformity and growth retardation
• Spleen becomes enlarged

54. Clinical manifestations of G6PD deficiency
• Two forms
• This form is self-limiting

55. Treatment
• Sickle cell anemia: prophylactic antibiotics
(Penicillin V 250 mg b.d), pneumococcal
vaccine, hydroxyurea is effective.
• Thalassemia: transfusion, desferroxamine and
deferiprone
• G6PD deficiency: causative oxidising agent
stopped and general supportive measures
adopted. No specific drug treatment for this
disorder