16.1 Anaemia

Definition

Anaemia is a common medical condition throughout all ages of childhood. However, the common causes vary with age. Anaemia refers to a reduction in haemoglobin (and hence red cell mass) below that which is considered normal for the patient in question. Normative haemoglobin data differs with age and, in teenage years, sex. Clinicians need to ensure that, when considering a diagnosis of anaemia, correct age-specific and, where applicable, sex-specific reference ranges are used. These reference ranges may vary according to the laboratory analyser in use. Thus each laboratory should report their own specific age-related reference ranges. An example of the age-related variation is shown by the reference ranges in Table 16.1.1. The majority of reference ranges in clinical use reflect 95% confidence intervals, so that 2.5% of individuals who are in fact ‘normal’ would be expected to consistently have haemoglobin levels just below the lower limit of the reported reference range.

Table 16.1.1 Normal haemoglobin values for age

Age	Haemoglobin (g/L)
Birth	135–200
1 month	100–180
2 months	90–140
6 months	95–135
1 year	105–135
2–6 years	110–145
6–12 years	115–155
> 12 years (female)	120–160
> 12 years (male)	130–180

Physiology

The prime function of haemoglobin is tissue oxygen delivery. Hence anaemia threatens this critical bodily function. Acutely, severe anaemia can lead to hypoxic tissue injury, and chronic anaemia can lead to growth failure and organ dysfunction as a result of chronic hypoxia or failure of compensatory mechanisms. The physiology of tissue oxygen delivery is critical to understand, as it enables the clinician to understand the concepts of relative anaemia and to determine appropriate treatment of the anaemic patient.

where 1.34 is a constant and represents the amount of oxygen carried by 1 g normal haemoglobin.

The key issues in this basic physiological equation are that:

• the parameters are multiplied, such that small decreases in cardiac output and haemoglobin and haemoglobin saturation lead to an overall large decrease in tissue oxygen delivery. Thus patients with cardiac disease may tolerate less reduction in haemoglobin before developing tissue hypoxia, and hence often have considerable urgency in treating their anaemia. No single haemoglobin (Hb) level can be used as an indication for transfusion therapy as these other factors need to be considered.

• in the presence of anaemia, cardiac output must be increased to maintain tissue oxygen delivery (Hb saturation cannot be increased above 100%). Failure of this compensatory mechanism or limitation of cardiac output by another disease will result in tissue hypoxia. Cardiac output is determined by cardiac stroke volume and heart rate. Therefore, heart rate is an important measure of the stress the anaemia is placing on the patient’s cardiac reserve. All anaemic patients should have their vital signs, especially heart rate and respiratory rate, assessed as part of their initial medical evaluation, and these parameters should be used to monitor progress and response to therapy.

• Hb saturation is normally close to 100% in children without cyanotic congenital heart disease or significant lung pathology. Thus, in otherwise well children with severe anaemia, or children in whom the Hb saturation is measured as 99–100%, inspired oxygen therapy makes little if any contribution to improving tissue oxygenation. Recovery of red cell mass (and hence Hb) is the most effective therapy.

• in children with cyanotic congenital heart disease or pulmonary pathology, the natural compensation for reduced Hb saturation is to increase Hb concentration. Hence, if a child with cyanotic congential heart disease who usually has a relatively increased Hb was to develop a ‘relative anaemia’, they might develop symptoms of anaemia at Hb levels that would be considered normal in most children. Treatment of ‘relative anaemia’, if required, is based on the same principles as treatment of ‘true anaemia’.

Clinical presentations

Children with anaemia most often present with pallor (reflecting the reduced Hb) or signs of reduced exercise tolerance (reflecting inability to increase tissue oxygen delivery to meet the demands of exercise). Reduced exercise tolerance manifests differently according to age. In infants, poor feeding is often described. In older children, shortness of breath on exertion or generalized lethargy are more common. Alternatively, incidental finding of anaemia when full blood examination has been performed for another indication is also very common.

Once the presence of anaemia has been confirmed, thorough history-taking and examination of the patient is required. Patient age and the duration of symptoms is important as a first step in determining the likely aetiology of the anaemia.

In addition, during the history and examination, other key considerations are:

• Is there evidence of cardiac decompensation or other adverse events as a result of the anaemia? This clearly makes appropriate therapy a matter of urgency.

• Are there clues to the aetiology of the anaemia?

• Is there evidence of multilineage cytopenias (neutropenia and thrombocytopenia)?

• Is there evidence of an associated, perhaps causative, disease?

Information that assists in answering these questions is shown in Table 16.1.2.

Table 16.1.2 Relevant information required on history and examination for patients with anaemia

Critical question	Information obtained on history and examination
Cardiac decompensation	Exercise tolerance
	Heart rate and respiratory rate
	Signs of congestive heart failure
	Altered conscious state, irritability, restlessness
Aetiology	Duration of symptoms (bone marrow failure and haematinic deficiency usually have a longer duration of symptoms)
	Family history (hereditary spherocytosis, G6PD deficiency, haemoglobinopathies and others are inherited causes of anaemia. Maternal history (e.g. veganism may be associated with B₁₂ deficiency in infants)
	Birth and neonatal history (blood loss at birth, birth asphyxia and maternal blood group compatibility are all important in assessing neonatal anaemia. Jaundice at birth may give a clue to an episodic haemolytic disorder in older children)
	Presence or absence of jaundice (haemolysis)
	Drug exposure: as a cause of haemolysis, or bone marrow suppression
	Blood loss: trauma, recent surgery, iatrogenic in neonates, epistaxis, menstrual loss
	Dietary history: iron deficiency can be predicted in infants less than 12 months of age fed cow’s milk, or in toddlers who have failed to transfer to solid foods adequately
Multilineage cytopenias	Bruising or bleeding, especially petechiae (thrombocytopenia)
Multilineage cytopenias	Infection, mouth ulceration (neutropenia)
Associated disease	Gastrointestinal symptoms (e.g. coeliac disease, inflammatory bowel disease)
	Joint or bone pain (e.g. leukaemia, sickle cell disease, arthritis)
	Renal disease
	Malignancy
	Infection: as a primary cause (e.g. malaria), a precipitant of acute deterioration in a more chronic anaemia, or a trigger to acute haemolysis
	Neurological disorders, developmental delay/regression, failure to thrive may reflect functional B₁₂ deficiency in infants. Pica may be associated with iron deficiency
	Eating disorders in older children
	Bleeding disorders