• Vitamin B₁₂ or folic acid

Anemia or Chronic disease
Aplastic Anemia congenital or acquired

• Auto-immune or iso-immune infections
• Physical or chemical agents

Intrinsic to red blood cell:

• Membrane defects
• Enzyme deficiencies (metabolic)
• Hemoglobinopathies: chain synthesis defects, amino acid substitutions.

Aplastic Anemia:

• Inadequate intake of diet.
• Impaired absorption.

• Pernicious anemia. 
• Gastrectomy (surgical removal of entire or part of the stomach).
• Congenital absence of inherent or intrinsic factor.

3) Disorder of the terminal ileum:

• Fish type worm infestation.
• Bacterial blind loop syndrome.

Vitamin B₁₂:

• Unbalanced diet
• Excessive cooking
• Common in alcoholics, teenagers, and sometimes in infants.
• Old age, poor conditions, starvation.

ii. Malabsorption:

• Tropical sprue
• Drugs (barbiturates, ethanol diphenylhydantoin).

iii. Increased requirements:

• Pregnancy, lactation, infancy, malignancy, increased hematopoiesis.

➤ Other causes:

• Mercaptopurine
• Fluorouracil
• Cytosine

Pernicious Anemia

Causes of Pernicious Anemia:

Same as causes of megaloblastic anemia.

Clinical features:

A patient with a folic acid deficiency may be asymptomatic, if the deficiency of folic acid is severed, he may present a complex clinical picture, since the malnutrition that is responsible for folic acid deficiency and also produces other deficiencies as well. It most cases the patient may appear obviously malnourished. The onset of the anemia is associated with non-specific symptoms such as weakness, weight loss, easy fatigue, some patient also give a history of lack of concentration, and insomnia. The patient also mentions the symptoms referable to the gastrointestinal tract. These include sore tongue and cheilosis/cheilitis (a disorder of the lips marked by scaling and fissures at the corners of the mouth). But remember this in contrast to vitamin B₁₂ deficiencies, neurological abnormalities do not occur.

Treatment:

This anemia is treated by giving a daily dose of 5mg of folic acid orally. Prophylactic folic acid is also advisable in pregnancy and in persistent hematological disorders, where there is rapid cell turnover. But remember this folic acid never be given other than with vitamin B₁₂ between of risk of aggravating neurological features of vitamin B₁₂ depletion.

Iron Deficiency anemia

This is the type of anemia it occurs when there is an inadequate amount of iron is present for hemoglobin synthesis.

Causes of Iron Deficiency anemia:

Nutritional deficiency:

1. Low intake
2. Increase in demand

• Pregnancy
• Infancy
• Lactation 
• Excess menstrual flow.

Malabsorption:

• Partial/complete gastrectomy
• Achlorhydria
• Steatorrhoea
• Celiac disease
• Intestinal tuberculosis

Acute/chronic blood loss:

• Peptic ulcers
•  Coloniccarcinoma
• Hemorrhoids
• Hookworm infections
• Bleeding disorders

Clinical features:

The symptoms of iron deficiency anemia are similar to all other anemia’s include fatigue, weakness, pallor complexion. Symptoms specific to iron deficiency anemia may include the epithelial changes, brittle nails and hairs, koilonychia (spoon-shaped nail), atrophy of the tongue, glossitis (inflammation of the tongue) and angular stomatitis, dysphagia (difficulty or discomfort in swallowing, as a symptom of the disease).

Treatment:

The correct line of treatment of iron deficiency anemia is to find and treat the underlying cause. Oral iron is advised in the form of ferrous sulfate in the dose of 600mg daily.
If the patient is intolerant of oral preparations due to Plummer Vinson’s syndrome, he may be advised parenteral iron.
Iron dextran can be given in doses of 50-250mg daily by deep intramuscular injections. It is better to give blood transfusion in a case when the Hb is less than 5mg%.

Hemolytic Anemia:

Hemolytic Anemia means (Break down of Red Blood Cells). In this type of anemia, there is early rupturing of the red blood cells and the release of hemoglobin. Different abnormalities of RBCs many of which are hereditary or acquired, make the cells very fragile so that they rupture easily. Even though the number of RBCs formed is completely normal. Their life is so short that it causes anemia.

Causes of hemolytic anemia:

Intracorpuscular abnormalities:

• Hereditary spherocytosis (RBCs are sphere-shaped).
• Sickle cell anemia.
• Thalassemia.

Extra corpuscular abnormalities:

• Erythroblastosis details.
• Autoimmune hemolytic anemia.
• Acquired hemolytic anemia due to toxins bacteria and physical agents.
• Malaria.
• Glucose 6 phosphate dehydrogenase deficiency.

Miscellaneous:

• Drugs damaging to RBCs, hypersplenism.

Hereditary Spherocytosis:

• Inherited, intrinsic, membrane defect
• RBCs – spheroidal, less deformable, and vulnerable to splenic destruction
• AD – 75%
• Rest autosomal recessive form
• Highest incidence in Northern Europe
• 1 in 5000
• Lifespan of RBC > 10-20 days

Treatment:

1. Folic acid 5 mg/day
2. Blood transfusion
3. Splenectomy is advisable in all the mild cases

Sickle Cell Anemia

• Painful swelling of the hands and feet.
• Chest pain.
• Fatigue and intolerance to exercise due to reduced Hb.
• Pallor, icterus, and splenomegaly.
• Haematuria (blood in urine).
• Development of immunity for plasmodium falciparum.

Diagnosis: 

• Sickling of normoblasts due to low oxygen tension.
• Hb is less than 8 gm% 
• The presence of HbS is demonstrated by the examination of RBCs.

Treatment:

• Sickle cell anemia is treated with folic acid and the infection is treated with antibiotics.
• Blood transfusion is advised when Hb is falling to 5 gm%.