Anemia

Introduction

 Anemia is not a single disease but a group of disorders in

which Hb concentration of blood is below the normal range for
the age and sex of the subject. Therefore anemia is labelled
when the Hb concentration is less than:
 13 g/dL in adult males,
 11.5 g/dL in adult females,
 15 g/dL in newborn, and
 9.5 g/dL at 3 months of age.
 Low RBC count (less than 4 million/μL) is usually, but not
always associated with low Hb levels in anemia.
Grading of Anemia

 Grading of anemia depending upon the level of

Hb, has somewhat arbitrarily been made as:
 Mild anemia – Hb 8–10 g/dL,
 Moderate anemia – Hb 6–8 g/dL and
 Severe anemia – Hb below 6 g/dL.
CLASSIFICATION

 Aetiological (Whitby’s) classification

 Types of anemia depending upon the causative mechanism are:
A. Deficiency anemias
 Iron deficiency anemia
 Megaloblastic anemia (pernicious anemia) due to deficiency of vitamin B12
 Megaloblastic anemia due to deficiency of folic acid
 Protein and vitamin C deficiency can also cause anemia.
B. Blood loss anemias or hemorrhagic anemias are commonly known and can be:
 Acute post-hemorrhagic anemia as in accidents and
 Chronic post-hemorrhagic anemia.
CLASSIFICATION

 Aetiological (Whitby’s) classification

C. Hemolytic anemias. These are relatively uncommon and
occur in conditions associated with increased destruction
of RBCs. These can be:
1. Hereditary hemolytic anemias, e.g. as seen in:
 Thalassemia,
 Sickle cell anemia,
 Hereditary spherocytosis and
 Glucose 6-phosphate dehydrogenase (G6PD) deficiency.
CLASSIFICATION

 Aetiological (Whitby’s) classification

2. Acquired hemolytic anemias such as
Immunohaemolytic anemia (due to antibodies against
RBCs)
 Hemolytic anemia due to direct toxic effects (e.g. in malaria,
snake venom, toxic effects of drugs and chemicals, etc.),
 Hemolytic anemia in splenomegaly and
 Hemolytic anemia in paroxysmal nocturnal hemoglobinuria.
CLASSIFICATION

 Aetiological (Whitby’s) classification

D. Aplastic anemia.
 Itoccurs due to the failure of bone marrow to produce
RBCs.
E. Anemia due to chronic diseases.
 It is seen in tuberculosis, chronic infections,
malignancies, chronic lung diseases, etc.
CLASSIFICATION

 Morphological (Wintrobe’s) classification

 Based on the mean cell volume (MCV), i.e. cell size and the
mean corpuscular hemoglobin concentration (MCHC), i.e.
hemoglobin saturation of RBCs, the anemias can be classified as:
1. Normocytic normochromic anemias. These are characterized
by normal MCV (78–94 μm3 or 78–94 μL) and normal MCHC (30–
38%). Such a morphological picture is seen in:
 Acute post-hemorrhagic anemia,
 Hemolytic anemias and
 Aplastic anemias.
CLASSIFICATION

 Morphological (Wintrobe’s) classification

2. Microcytic hypochromic anemias. These are characterized by reduced
MCV (< 78 μm3) and reduced MCHC (< 30%). Examples of such anemias are:
 Iron deficiency anemia,
 Chronic post-haemorrhagic anemia and
 Thalassemia.
3. Macrocytic normochromic anemia. It is characterized by increased MCV
(> 94 μm3) and normal MCHC (30–38%). Examples are:
 Megaloblastic anemia (pernicious anemia) due to deficiency of vitamin B12 and
 Megaloblastic anemia due to deficiency of folic acid.
IRON DEFICIENCY ANAEMIA

 Iron deficiency anemia is the commonest nutritional

deficiency disorder present throughout the world,
but its prevalence is higher in the developing
countries. In India, iron deficiency is the
commonest cause of anemia. Iron deficiency
anemia is much more common:
 In women between 20–45 years than in men,
 At periods of active growth in infancy, childhood and
adolescence.
CAUSES OF IRON DEFICIENCY ANAEMIA

 Causes of iron deficiency vary with age, sex and country of residence
of patient. In general, the causes of iron deficiency anemia can be
grouped as:
1. Inadequate dietary intake of iron as in:
 Milk fed infants,
 Poor economic status individuals,
 Anorexia, e.g. in pregnancy and
 Elderly individuals due to atrophy and poor dentition.
2. Increased loss of iron (as blood loss) from the body, e.g.
 Uterine bleeding in females in the form of excessive menstruation, repeated
miscarriages, postmenopausal bleeding, etc.
CAUSES OF IRON DEFICIENCY ANAEMIA

3. Increased demand of iron as in:

 Infancy, childhood and adolescence,
 Menstruating females and
 Pregnant females.
4. Decreased absorption of iron, as seen in:
 Partial or total gastrectomy,
 Achlorhydria and
 Intestinal malabsorption diseases.
Characteristic features of iron
deficiency anemia
 Nails become dry, soft and spoon-shaped (koilonychia).
 Tongue becomes angry red (atrophic glossitis).
 Mouth may show angular stomatitis.
 Oesophagus may develop their membranous webs at the
postcricoid area leading to dysphagia (Plummer– Vinson
syndrome).
Laboratory findings

1. Blood picture and red cell indices

 Hb concentration is decreased.
 RBCs are hypochromic (deficient in Hb) and microcytic
(smaller in size). They show anisocytosis and
poikilocytosis.
 Red cell indices like MCV, MCH and MCHC are
decreased.
Laboratory findings

2. Bone marrow findings

 Marrow cellularity: Erythroid hyperplasia,
 Erythropoiesis: normoblastic and
 Marrow iron: Deficient.
3. Biochemical findings
 Serum iron decreases, often under 50 mg% (normal 60–160 mg
%).
 Serum ferritin is very low indicating poor tissue iron stores.
 Total iron binding capacity is increased.
Treatment

Treatment of iron deficiency anemia consists of:

 Oral administration of Fe2+ salts and
 Correction of causative factor if possible.
MEGALOBLASTIC ANAEMIA

 Megaloblastic anemias are characterized by the

abnormally large cells of erythrocyte series. These are
caused by defective DNA synthesis due to deficiency of
vitamin B12 and/or folic acid (folate).
 AETIOLOGICAL TYPES
I. Megaloblastic anaemia due to vitamin B12 deficiency
II. Megaloblastic anemia due to folate deficiency
Megaloblastic anaemia due to vitamin B12
deficiency

 Causes of vitamin B12 deficiency are:

1. Inadequate dietary intake may occur in:
 Strict vegetarians and
 Breast-fed infants.
2. Malabsorption of vitamin B12 is more often the cause of deficiency and may
be due to:
 Gastric causes leading to the deficiency of intrinsic factors such as an autoimmune
cause of failure of secretion of intrinsic factor (Addisonian pernicious anemia),
gastrectomy and congenital lack of intrinsic factor.
 Intestinal causes which are associated with decreased vitamin B12 absorption are
tropical sprue, ileal resection, Crohn’s disease, fish tapeworm infestation and
intestinal blind loop syndrome.
Addisonian pernicious anemia

 Aetiology. Addisonian pernicious anemia is the term

which is used specifically for the megaloblastic anemia
due to vitamin B12 deficiency occurring as a result of
failure of secretion of intrinsic factor by the stomach
owing to an autoimmune atrophy of gastric mucosa. Thus,
pernicious anemia is an autoimmune disease and in about
50% of patients, antibodies to intrinsic factor can be
demonstrated. The disease is rare before the age of 30
years, occurs mainly between 45 and 65 years, and affects
females more frequently than males.
Specific features of pernicious anemia

Specific features of pernicious anemia are:

 Anti-intrinsic factor antibodies in serum (present in 50%
cases)
 Abnormal vitamin B12 absorption test corrected by the
addition of intrinsic factor (Schilling test).
Megaloblastic anemia due to folate
deficiency
 Causes of folate deficiency are:
1. Inadequate dietary intake due to poor intake of
vegetables as seen in poor people, infants and alcoholics.
2. Malabsorption, e.g. in coeliac disease, tropical sprue and
Crohn’s disease.
Megaloblastic anemia due to folate
deficiency
3. Increased demand as occurs in:
 Physiological conditions, such as pregnancy, lactation and infancy
and
 Pathological conditions of cell proliferation, such as increased
haematopoiesis (as in hemolysis) and malignancies.
4. Effect of drugs, such as certain anticonvulsants (e.g.
phenytoin), contraceptive pills and certain cytotoxic drugs
(e.g. methotrexate).
5. Excess urinary folate loss, e.g. in active liver disease and
congestive heart failure.
Specific features of folate deficiency

 Low serum folate levels

 Low red cell folate levels.
Characteristic features of megaloblastic
anemia

1. Blood picture and red cell indices

 Hb level is low.
 RBCs are larger in size (macrocytosis) but contain a
normal concentration of Hb (normochromic).
 MCV increases to 95–160 μm3 (normal 78–94 μm3).
 MCH increases to 50 pg (normal 28–32 pg).
Characteristic features of megaloblastic
anemia

1. Blood picture and red cell indices

 MCHC usually normal (35 ± 3%) because both MCV and MCH
increase. In late stages, MCHC may decrease.
 Peripheral smear shows nucleated RBCs with marked
anisocytosis and poikilocytosis.
 Reticulocyte count increases to more than 5% (normal less than
1%).
 Life span of RBCs is decreased.
 WBCs and platelets decrease because of encroachment of
megaloblastic tissue.
Characteristic features of megaloblastic
anemia

2. Bone marrow picture

 Bone marrow shows megaloblastic hyperplasia
characterized by presence of:
 70% proerythroblasts and early normoblasts (normal 30%)
and
 30% intermediate and late normoblasts (normal 70%).
 Marrow iron. Prussian blue staining for iron in the
marrow shows an increase in the number and size of
iron granules in the erythroid precursors.
Characteristic features of megaloblastic
anemia

2. Bone marrow picture

Characteristic features of megaloblastic
anemia

3. Biochemical finding
 Serum bilirubin increases more than 1 mg/dL (normal
0.2–0.8 mg/dL) due to excessive destruction of RBCs in
spleen, liver and bone marrow.
 Urine urobilinogen excretion may increase due to
increased serum bilirubin.
 Serum iron and ferritin is usually increased because
iron is not utilized by the immature RBCs.
Characteristic features of megaloblastic
anemia

3. Biochemical finding
 Serum vitamin B12 levels are decreased (normal 200– 900
pg/mL) in patients with megaloblastic anemia due to
vitamin B12 deficiency.
 Serum folate levels are decreased in the patients with
megaloblastic anemia due to folic acid deficiency.
 Red cell folate levels are more reliable indicator of tissue
stores of folate than serum. In folic acid deficiency, red
 cell folate levels are decreased.