Anaemia

Introduction to Anaemia

Anaemia is a reduction in the haemoglobin concentration in the peripheral blood below the normal range expected for the age and sex of an individual.

The World Health Organisation (WHO)defines anaemia by the following haemoglobin (Hb) concentrations:

Males

• < 130 g/L (130-175 g/L) or
• < 13.5 gram/100 ml.)

Females

• < 120 g/L (120-155 g/L) or
• < (12.0 gram/100 ml.)

In pregnancy, a Hb < 110 g/L is diagnostic.

The determination of haemoglobin concentration should always take the state of hydration and altitude of residence of the individual into consideration.

Anaemia can be classified on the basis of red cell morphology and aetiology or pathogenesis.

Classification of Anaemia

Morphological classification

1. Macrocytic Megaloblastic:
   1. Folic acid deficiency
   2. Vitamin B 12 deficiency
   3. Inherited disorders of DNA synthesis
2. Non-megaloblastic:
   1. Accelerated erythropoiesis
   2. Increased membrane surface area
   3. Obscure
3. Hypochromic-microcytic:
   1. Iron deficiency
   2. Other disorders of iron metabolism
   3. Disorders of globin synthesis
4. Normochromic-normocytic:
   1. Recent blood loss
   2. Hypoplastic bone marrow
   3. Infiltrated bone marrow
5. Haemolytic anaemias
   1. Endocrine abnormality.
   2. Chronic disorders
      1. Renal disease
      2. Liver disease

Classification based on aetiology and pathogenesis

1. Blood Loss: Acute Chronic (leads to iron deficiency)
2. Increased red cell destruction (haemolytic anaemias): Corpuscular defects (intracorpuscular or intrinsic abnormality)
3. Disorders of the membrane e.g. elliptocytosis, spherocytosis
4. Disorders of metabolism e.g. Glucose-6 Phosphate dehydrogenase deficiency, Haemoglobinopathy e.g. sickle cell disease, Paroxysmal nocturnal haemoglobinuria.
5. Abnormal haemolytic mechanisms (extra corpuscular or intrinsic abnormality)
6. Autoimmune
7. Rhesus-incompatibility, mismatched transfusion, hypersplenism
8. Infections e.g. malaria, Clostridium welchii, drugs and toxins
9. Others e.g. burns decreased red cell
10. Nutritional (due to deficiencies of production substances essential for erythropoiesis)
    1. Iron Folate
    2. Vitamin B12
    3. Various deficiencies e.g. protein, ascorbic acid
11. Bone marrow stem cell failure:
    1. (Primary (idiopathic):
       1. Aplastic anaemia
       2. Pure red cell aplasia
    2. Secondary:
       1. Drugs (phenylbutazone, cytotoxic agents, etc).
12. Chemicals
13. Irradiation
14. Anaemias associated with systemic disorders:
    1. Infection
    2. Liver disease Renal disease
    3. Connective tissue disease
    4. Cancer (including leukaemia)
    5. Marrow infiltration
    6. Thyroid or pituitary disease.

Clinical features of Anaemia

This depend on the degree of anaemia, severity of the causative disorder and age of the patient.

The clinical effects of anaemia are due to
anaemia itself and the disorder(s) causing it.

Common:

Tiredness, lassitude, weakness, dyspnoea on exertion, palpitations, pallor

Less common:

Angina of effort, faintness, giddiness,
headache, ringing in the ears, high output state congestive cardiac failure.

Differential diagnoses

• Cardiac failure
• Respiratory failure

Complications of Anaemia

Cardiac failure

Investigations

1. Haematologic: Haematocrit, haemoglobin concentration, red cell indices, reticulocyte count, total leukocyte and differential counts,
   platelet count
2. Erythrocyte sedimentation rate,
3. Blood film examination for morphology of cells, thick and thin films for malaria parasites.
4. Urine analysis: Colour, pH, clarity, and specific gravity, microscopic examination of fresh urine specimen, protein, glucose, occult blood
5. Stool: Colour, consistency, examination for ova and parasites, occult blood
6. Plasma: Blood Urea Nitrogen (BUN), Total protein and albumin bilirubin, creatinine (if BUN is abnormal)
7. Others:
   1. Coombs test for the presence of antibodies to red cells
   2. Ham’s test (acidified serum test)
   3. Bone marrow aspiration and trephine biopsy
   4. Haemoglobin electrophoresis Sickling test (metabisulphite and solubility)
   5. Family studies

Treatment objectives

• Restore haemoglobin concentration to normal levels.
• Prevent/treat complications

Supportive measures

• Bed rest in severe cases: initially necessary, especially when cardiovascular symptoms are prominent.
• Treat cardiac failure by standard measures.
• Balanced diet with adequate protein and vitamins.
• Correct dietary deficiencies (e.g. iron, folic acid)
• Blood transfusion: a very important measure in the treatment of anaemia, but should not be used as a substitute for investigation, or specific treatment of the cause
• Arrest blood loss
• Treat any underlying systemic disorder.
• Remove any toxic chemical agent or drug
• Correct anatomical gastro-intestinal abnormalities

Drug treatment for Anaemia

Haematinics e.g. iron, vitamin B, folic acid.

• The specific haematinic indicated should be given alone
• Response to adequate treatment is important in confirming diagnosis

Iron deficiency:

Oral iron therapy:

• • Ferrous sulfate 200 mg (containing 65 mg of iron) tablet 2-3 times daily
  • Treat for 3- 6 months to correct deficits in haemoglobin

Parenteral therapy:

• • Not necessary unless there is intolerance to oral iron
  • Indications for parenteral iron:
    • Anaemia diagnosed in late pregnancy.
    • Correction of anaemia just before an operative procedure
    • Haemorrhage expected to continue unabated.

Iron preparations:

• Iron dextran given as “total dose” infusion, By deep intramuscular injection into the gluteal muscle or by slow intravenous injection or by intravenous infusion, calculated according to body weight and iron deficit dose in mL (of 50 mg/mL. preparations) = [Patient’s wt. in kg X (14 Hb in g/dL)-10
• Periodic hematologic determination of haemoglobin and hematocrit is a simple and accurate technique for monitoring haematological response and should be used
  as a guide in therapy.
• Evidence of therapeutic
  response can be seen in a few days as an increase in reticulocyte count

Notable adverse drug reactions, caution

1. Oral iron preparations:

• Nausea, epigastric pain, diarrhoea, constipation, skin eruptions.
  • Reduce dosage and frequency of administration to reduce these effects

2. Parenteral iron:

• Local reactions: phlebitis and lymphadenopathy
• Systemic reactions may be early or late headache, fever, vomiting, general aches and pains, backache, chest pain, dyspnoea, syncope: death from anaphylaxis
• Test doses are no longer recommended but caution is needed with every dose of intravenous iron
• Patients should be monitored for signs of hypersensitivity during and for at least 30 minutes after every administration
• Total-dose infusion should be avoided in patients with history of allergy
• Not recommended for children under 14 years
• Avoid in first trimester and use in the second and third trimesters only when the benefit outweighs the potential risks for both mother and fetus
• Anaphylaxis and other Hypersensitivity can occur with parenteral iron and facilities for cardiopulmonary resuscitation must be available
• Discontinue oral iron prior to administration of iron dextran injection.
• Oral iron should not be given until 5 days after last injection

Megaloblastic anaemia

Response to therapy is satisfactory if administered dose is limited to the minimal daily requirement
Treatment with vitamin B12 (cobalamin) to replace body stores

• Six-1000 micrograms intramuscular
  injections of hydroxocobalamin given at 3 -7 day intervals
• Maintenance therapy: patients will need to take vitamin B12 for life
• 1000 micrograms hydroxocobalamin intramuscularly once every 3 months

Notable adverse drug reactions, caution

• Toxic reactions are very rare and are usually not due to cobalamin itself
• Pharmacologic doses of folic acid produce haematological response in vitamin B12 -deficient patients but worsen the neurological complications

• Large doses of vitamin B, also give haematological response in folate-deficient patients

Prevention of Anaemia

• Balanced diet
• Prompt treatment of all illnesses