2. Introduction
ā¢ Not a single disease
ā¢ Results from a number of different pathologies
ā¢ Defined as a reduction from the normal quantity of
Hb in blood
ā¢ Who defines anemia as Hb levels less than 13 g/dl for
males and less than 12 g/dl for females
ā¢ Low Hb levels results in decreased oxygen carrying
capacity of blood
3. Epidemiology
ā¢ Most common condition resulting in significant
morbidity and mortality
ā¢ 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 (contdā¦)
ā¢ 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 (contdā¦)
ā¢ Erythropoietin production si impaired n
condictions such as RA, cancer and Sickle cell
anemia
ā¢ Each day about 2 *1011 erythrocytes enter
the circulation
ā¢ Normally survive for 120 days
8. Normal erythropoiesis (contdā¦)
ā¢ Destroyed by reticuloendothelial system
found in spleen and BM
ā¢ Iron is removed from haem component of Hb
and transported back into bone marrow for
reuse
9. Normal erythropoiesis (contdā¦)
ā¢ Pyrole ring from globin is excreted as
conjugated bilirubin by the liver and the
polypeptide portion enters the bodyās protein
pool
10. Clinical manifestations
ā¢ Mildest form: tiredness and lethargy, reduced
mental performance
ā¢ 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
ā¢ No place for blind treatment
ā¢ Anemia is a consequence of reduced concentration of Hb in
each red cell and/or reduced number of red cells in peripheral
circulation
ā¢ Imp parameter: Hb concentration of blood, including its size ,
shape and color, MCV to determine type of anemia
ā¢ Bone marrow examination
12. Iron deficiency anemia
ā¢ Epidemiology: 20% of worldās population
ā¢ Cause: diet deficient in iron, parasitic infestations
and multiple pregnancies
ā¢ Aetiology: Blood loss, GI bleeding (most likely),
Haemorrhoids, nosebleeds or postpartum
haemorrhage
13. Iron deficiency anemia
Causes of Iron deficiency anemia
ā¢ Inadequate iron absorption
Dietary deficiency
Malabsorption
ā¢ Increased physiological demand
ā¢ Loss through bleeding
14. Pathophysiology
ā¢
ā¢
ā¢
ā¢
Elimination not controlled physiologically
Homeostasis maintained by controlling iron absorption
Absorption inefficient
Iron bound to haem is better absorbed than iron
found in vegetables
ā¢ Phosphates and phytates leads to formation of
unabsorbable complex, while ascorbic acid increases
iron absoprtiopn
15. Pathophysiology (contdā¦)
ā¢ Anemia a result of mismatch between bodyās
iron requirement and iron absoprtion
ā¢ Fortified milk given to children up to the age of
18 months increases Hb levels and improve
performance
ā¢ Iron malabsoprtion occurs in patients with
coleliac disease and in 50% patients following
gastrectomy
16. Pathophysiology (contdā¦)
ā¢ During pregnancy: dilutional anemia
ā¢ Some of the increased demand is met by
stopping menstruation
Whatever the cause might
be
inadequate iron
absorption leads
to anemia
18. Investigations
ā¢ Serum iron, Total iron binding capacity (TIBC)
and serum ferritin
ā¢ Aim: To correct anemia and replenish iron
stores
Important to resolve the
underlying cause as far
as possible
19. Treatment
ā¢ Folic acid use during pregnancy
ā¢ Prophylaxis in menorrhagia, after partial
gastrectomy and in some low birth weight
infants
ā¢ Continue for 6 months to both correct anemia
and replenish body stores
ā¢ Standard treatment: 200 mg three times a day
20. Treatment (contdā¦)
ā¢ It takes 1 to 2 weeks for Hb level to rise to 1
g/dl
ā¢ N and abdominal pain occurs in some patients
ā¢ Alternative salts of iron are tried
ā¢ Absorption is 15% of intake during the first 2-3
weks but falls off to an average of 5%
thereafter
ā¢ Modified release oral preparations also
available
21. Treatment (contdā¦)
ā¢ There is little place for parenteral iron
ā¢ In renal patients, a regular weeks dose is often
given and patientsā serum ferritin monitored
to check for iron overload
22. MEGALOBLASTIC ANEMIA
ā¢ They are macrocytic anemia (raised MCV)
ā¢ Abnormality in the maturation of
haemopoietic cells in the bone marrow
ā¢ Two causes: Folate deficiency and Vit. B12
deficiency anemia
ā¢ Pernicious anemia is a specific disease caused
by malabsorption of Vit B12
23. Aetiology
Folate deficiency anemia
ā¢ Readily available in normal diet (Fruit, green
vegetables and yeast)
ā¢ Folate deficiency either due to folic acid
deficiency anemia or increased folate
utilization
24. Aetiology (contdā¦)
Vitamin B12 deficiency anemia
ā¢ Inadequate intake or malabsorption (dueto
removal of distal ileum)
ā¢ Dietary source: Food of animal origin
ā¢ Daily requirements: 1-2 micrograms
27. Pathophysiology of Vit. B12 deficiency anemia
ā¢ Absorption occurs by an active process
ā¢ Enzyme in the stomach release Vit. B12 from protein complexes
ā¢ One molecule of Vit. B12 combine with one molecule of
glycoprotein (called intrinsic factor)
ā¢ There are specific receptors in the distal ileum for intrinsic
factor-Vit B12 complex
ā¢ Vit B12 enters the ileal cell and is then transported through the
blood attached to transport proteins
ā¢ A total gastrectomy always leads to Vit. B12 deficiency
ā¢ Onset of anemia is usually delayed
28. Pathophysiology of pernicious anemia
ā¢ Autoimmune in origin
ā¢ Patients typically have a gastric atrophy and no or
virtually no intrinsic factor secretion
ā¢ Two different intrinsic factor antibodies have been
produced in serum of patients with pernicious
anemia
ā¢ Gastric parietal antibodies found (in 90% patients)
32. Treatment
ā¢ 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
ā¢ Replacement therapy
ā¢ Duration of treatment depends on cause
ā¢ Changes in dietary habit or removal of any
precipitating factor
ā¢ Normal daily requirement approx. 100 micrograms
per day
ā¢ Dose: 5-15 mg per day for 4 months
ā¢ Parenteral folic acid treatment not normally required
34. Treatment of folate deficiency anemia
during pregnancy
ā¢ Folate requirement increases in pregnancy
and is higher in twin pregnancies
ā¢ Prophylaxis with folate ( 350-500 micrograms)
frequently given during pregnancy
35. Treatment of Vit. B12 deficiency anemia
ā¢ Require life long replacement therapy
ā¢ Transfusion not normally given
ā¢ If emergency transfusion deemed necessary, packed cells may
be given
ā¢ Diuretics also given
ā¢ Definite diagnosis should be made before starting treatment
ā¢ 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
ā¢ Group of conditions diagnosed by finding ring
siderobalst in the BM
ā¢ Both hereditary and acquired forms present
37. Aetiology
ā¢ In hereditary forms, there is X chromosome
linked pattern of inheritance
ā¢ Both autosomal dominant and autosomal
recessive families present
ā¢ Defect: Reduced activity of the enzyme 5aminolevulinate synthase (ALAS)
38. Pathophysiology
ā¢ Examination of BM shows number of
erythroblasts that have iron granules
surrounding the cell nucleus (known ad ring
sideroblast)
ā¢ Low levels of ALAS in hereditary forms
ā¢ Drugs and toxins: Alcohol, Isoniazid in slow
acetylators, Dose of Chloramphenicol over 2 g
39. Clinical manifestations
ā¢
ā¢
ā¢
ā¢
Develop on infancy or childhood
Severe or mild anemia
Splenomegaly
Idiopathic forms tends to develop insiduously
(middle age or later)
ā¢ Many becoem asymptomatidc for long
periods
40. Investigations
ā¢ In heriditary fomrs: red cells in peripheral blood are
hypochromic and microcytic
ā¢ Increased iron stores in BM
ā¢ Serum iron and ferritin high
ā¢ In acquired forms: Peripheral blood has hypochromic
cells which may be either normocytic or macrocytic
ā¢ Common finding: Presence of sideroblast in BM
41. Treatment
ā¢ For hereditary forms: 200 mg daily Pyridoxine
ā¢ Frequent blood transfusion required in
unresponsive patients
ā¢ Desferrioxamine given i.v or s.c
ā¢ Oral Vit. C
42. Hemolytic anemias
ā¢ Reduced life span of erythrocytes
ā¢ Imbalance between rate of destruction and
rate of production
ā¢ Presence of both genetic and acquired
disorders
43. Aetiology of Sickle cell anemia
ā¢ They have a different form of Hb (Hb S)
ā¢ Patients with homozygous Hb S develop many
problems including anemia
ā¢ Sickle cell trait is usually asymptomatic
ā¢ 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
ā¢
44. Aetiology of Thalassaemias
ā¢ No alpha chain production or reduced
production of a chain
ā¢ Heterozygotes are symptomless
45. Aetiology of G6PD deficiency
ā¢ Large variants of G6PDdeficiency
ā¢ It is an enzyme involved in the production of
reduced glutathione
46. Pathophysiology of Sickle cell disease
ā¢ Membrane of red cells containing Hb S is
damaged (lead to IC dehydration)
ā¢ Polymerization of Hb S occurs when the
patients blood is deoxygenated
ā¢ These two processes lead to crescent-shaped
cells (known sickle cell)
47. Pathophysiology of Sickle cell disease
(contdā¦)
ā¢ Sickle cells are less flexible than normal cells
ā¢ This leads to local tissue hypoxia
ā¢ Anemia results from an increased red cell
destruction
48. Pathophysiology of Thalassemia
ā¢ Reduced or absent production of globin beta chain
ā¢ Leads to relative excess of alpha chain, when
unpaired become unstable and precipitate in red cell
precursors
ā¢ Ineffective erythropoiesis
ā¢ In alpha thalassemia, deficiency of alpha chain leads
to an excess of beta or gamma chains
49. Pathophysiology of Thalassemia (contdā¦)
ā¢ 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
ā¢ Essential for the production of reduced form
of NADPF in RBC
ā¢ NADPH is needed to keep gluthathione in
reduced form
ā¢ Glutathione helps RBC deal with oxidative
stress
ā¢ In G6PD deficiency Hb becomes oxidised and
Heinz bodies are form
52. Clinical manifestations of Sickle cell anemia
ā¢ 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
ā¢ Causes Erythropoietin production to increase
andresulst in expansion of BM
ā¢ Bone deformity and growth retardation
ā¢ Spleen becomes enlarged
55. Treatment
ā¢ Sickle cell anemia: prophylactic antibiotics
(Penicillin V 250 mg b.d), pneumococcal
vaccine, hydroxyurea is effective.
ā¢ Thalassemia: transfusion, desferroxamine and
deferiprone
ā¢ G6PD deficiency: causative oxidising agent
stopped and general supportive measures
adopted. No specific drug treatment for this
disorder