History

• Symptoms attributable to anaemia include whitening of the body, lethargy, dyspnoea easy fatigue, irritability and reduced appetite.
• Symptoms that suggest hemolysis are jaundice, yellow or dark-coloured urine
• Other symptoms include nose bleeding, haematochezia, black stool, haematemesis and menorrhagia.
• Pica (intense craving for non-food items e.g. sand (geophagia), ice (pagophagia) suggests iron deficiency.
• A history of recurrent blood transfusions could suggest cancers, chronic kidney disease or haemolytic anaemias.
• Chronic anaemia or a family history of anaemia– may suggest inherited anaemia e.g. spherocytosis, haemoglobinopathy. History to suggest sickle cell anaemia includes recurrent hand and foot swelling, jaundice and whitening of the palms and soles of the feet
• A child on a strictly vegan diet would suggest vitamin B12 deficiency
• The drug history is also important as some medications can cause bone marrow suppression (e.g. chemotherapy) or induce haemolysis (e.g. in patients with G6PD deficiency)

Physical examination

Detailed physical examination may provide important clues to the cause of anaemia. 

• Pallor is assessed by examining sites where capillary beds are visible (eg, conjunctiva, palm, soles). 
• Signs of haemolysis- scleral icterus, jaundice, and hepatosplenomegaly resulting from increased red cell destruction.
• Signs of decompensation- tachycardia, bounding pulse, tachypnoea, third heart sound, cardiac murmurs, displaced apex beat
• Skin- petechiae/ecchymoses (bleeding disorder)
• Oral- glossitis and macroglossia are seen in pernicious anaemia and vitamin B12 deficiency; angular cheilitis is seen in iron deficiency.
• Lymphadenopathy- seen in infection, malignancy
• Splenomegaly- a pointer to haemolysis, sequestration or malignancy.

Basic investigations used to focus the diagnostic considerations and guide further testing to confirm the aetiology of anaemia include:

1. Full blood count (FBC) with red blood cell (RBC) indices 
2. Peripheral blood smear/film
3. Reticulocyte count

• FBC analysis

Anaemia with leukocytosis- most commonly suggests an infectious aetiology or, less commonly, acute leukaemia. 

Hypersegmented neutrophils- suggest vitamin B12 deficiency. 

Anaemia with thrombocytosis is a common finding in iron deficiency.

Anaemia with thrombocytopenia is seen in HUS, Evans syndrome and severe iron deficiency. Pancytopenia- may signify abnormal bone marrow function or increased peripheral destruction of blood cells.

• Reticulocyte count

The reticulocyte count indicates bone marrow erythropoietic (RBC production) activity. It is used to classify the bone marrow response to anaemia. The reticulocyte count is especially helpful in evaluating children with normocytic anaemia. Anaemia with a high reticulocyte count (>3 per cent) reflects an increased bone marrow RBC production in response to hemolysis or blood loss. Anaemia with a low or normal reticulocyte count reflects deficient production of RBCs. iei.e., a reduced marrow response to the anaemia as seen in infections, lead poisoning, drugs (e.g. chemotherapy) etc.

• Blood smear/film 

It may reveal abnormal cells that can help identify the cause of the anaemia e.g. RBC size, central pallor, fragmented cells, blast cells, sickle cells, spherocytes, stomatocytes, poikilocytes, target cells, bite cells, etc.

A thorough medical history, physical examination and initial laboratory tests are important to narrow the diagnostic possibilities and guide further tests.

• Check for abnormalities in other cell lines from FBC

• Classify anaemia using the RBC indices

• Study reticulocyte response

Do confirmatory testing for likely cause e.g. direct antiglobulin test (Coombs), G6PD deficiency screening test, haemoglobin (HGB) analysis/electrophoresis, serum ferritin, bone marrow aspiration and cytology, malaria parasite check, stool microscopy , blood culture, etc.

This depends on the underlying cause and severity of the anaemia. 

Options include blood transfusion; haematinic medications/supplementation- e.g. iron, folate, vitamin B12; erythropoietin therapy; treatment/management of underlying illness.

Anaemia is a common presentation in paediatric practice. It is always important to look for the secondary cause. As the causes are numerous, adequate knowledge of evaluating a patient with anaemia is important.