Anaemia in children

Essentials

  • Leukaemias, haemolytic crises and bleedings should be readily identified as these conditions require immediate further investigations and treatment.
  • The underlying cause of iron deficiency should be revealed and adequate response to iron medication ensured.
  • Note the age-dependent variation of blood haemoglobin concentration:
    • at birth > 150 g/l
    • 1–4 months > 100 g/l
    • 5 months–5 years > 105 g/l
    • 6–15 years > 115 g/l

Examinations in primary health care

  • Register the general condition, colour of the eyes (conjunctivae), jaundice, signs of infection, pains, lymph nodes, size of liver, spleen and testes, cardiovascular functions, signs of bleeding, oedema.
  • Examine complete blood count, red cell morphology, reticulocyte count and sedimentation rate.
  • The appearance of small erythrocytes during the development of iron deficiency and disappearance in response to therapy may only be seen on histogram (increased RDW, red cell size distribution width) or by microscopy.
  • Exceptionally high RDW is a sign of e.g. mild iron deficiency in which the haemoglobin concentration and the MCV may still or already be normal.
    • Small MCV usually is a sign of iron deficiency, but it may also be caused by thalassemias (Thalassaemias) (usually minor), haemoglobinopathies (HbS, HbE etc.), recurrent infections, inflammation, or a tumour.
    • If the MCV is not small (normocytic or macrocytic anaemia), consult a paediatric haematologist or paediatrician (usually a direct Coombs test, liver and kidney function tests, folate and vitamin B12, and faecal and urinary blood search are recommended).
    • The patient may have iron deficiency even if haemoglobin concentration and MCV were normal. In unclear cases, determine soluble transferrin receptor (sTfR: increased concentration seen in iron deficiency and in accelerated production of red blood cells, decreased in suppression of red blood cell production) and ferritin (decreased in iron deficiency, may be increased – independent of iron stores – by infections or inflammations and in hepatic and malignant neoplastic diseases). Serum hepcidin concentration is reduced in iron deficiency and increased in inflammatory reaction.
  • If a child has a pure anaemia with normal other blood cells, the direct Coombs test is negative and he/she is not bleeding, prompt action is unnecessary. If a child with anaemia has positive result in direct Coombs test, he/she has autoimmune haemolytic anaemia (AIHA (Haemolytic anaemia)) and is immediately referred to a paediatric hospital to receive corticosteroid therapy.
  • If other cell lines are also deviant and the patient does not have an infection that would explain the abnormality, suspect leukaemia and refer the child immediately to a hospital with preparedness for bone marrow examination and treatment of leukaemia.

Evidence Summaries

Treatment of iron deficiency anaemia

  • If the haemoglobin and MCV values are low, but in line with each other, the child usually has iron deficiency anaemia. Start oral iron replacement (Fe++) at a dose of 4 mg/kg/day in 1–3 doses, preferably taken into an empty stomach. Taking the iron replacement preparation with juice that contains vitamin C (e.g. orange juice) improves the absorption of iron. The treatment response seems to be at least as good even if the daily dose is taken every second day only.
    • The number of iron preparations suitable for children has been declining over the recent years. Liquid products are available as Fe++ ferrous salts (Enfamil Fer-in-Sol® and Niferex®) and as Fe+++ hydroxide polymaltose complex (Maltofer®).
  • Iron therapy should be carefully implemented because iron deficiency may cause impairment of cognitive capacity at least in infants. On the other hand, iron therapy should not be unnecessarily continued because iron excess is harmful (Haemochromatosis).
  • Follow up haemoglobin after two weeks, and if possible, reticulocyte count (plus histogram or red blood cell morphology by microscopy). The diagnosis was correct if a treatment response is observed. Reticulocytosis and an increase in RDW are clearly more rapid measures of successful iron therapy than the raised haemoglobin value.
  • Continue iron medication for at least three months after haemoglobin has normalized.
  • Iron therapy may be discontinued when the ferritin concentration is normalised (provided that there is no acute phase reaction ongoing). Ferritin usually is an indicator of iron storage size.
  • When the diet has provided too little iron, correcting the child's nutrition is an important part of therapy. Consumption of milk should be limited to a maximum of 500 ml per day.

Evidence Summaries

Investigating the cause of iron deficiency

  • Iron deficiency is merely a symptom, not a disease. Find its cause. In cases of poor response to iron medication, think again! Look for dietary causes for insufficient intake of iron (especially in small children), for malabsorption and for blood loss due to bleeding (in older children in particular).
    • Diet history (too much milk?) and, if necessary, a diary of one week's meals
    • Colour of stools (black?)
    • Growth curves; relevant antibodies in the serum for the detection of coeliac disease (Coeliac disease), if indicated.
    • Tests for blood in urine and stool (blood is examined from three stool samples)
    • Refer to a paediatric hospital if blood is detected in the stools (sedimentation rate, endoscopies, Meckel scan). Possible diagnoses include Meckel's diverticulum or terminal colitis, in older children ulcerative colitis (Ulcerative colitis) or Crohn's disease (Crohn¹s disease).
    • Sometimes anaemia of a pre-school-aged child results from occult gastrointestinal bleeding associated with excessive intake of cow's milk. The child may also have hypoproteinaemia that responds to iron medication. Usually the child drinks large amounts of milk, and reduction of milk consumption can be recommended on the basis of history alone. Total abstinence is not necessary.

Investigations and treatment of anaemia at the hospital

  • If a direct Coombs test is positive: the child has autoimmune haemolytic anaemia (AIHA). Start prednisolone immediately with 2–4 mg/kg/day in three doses. RBC transfusion is given only in emergency.
  • If the child has Coombs-negative haemolytic anaemia, and spherocytes are seen on a blood film during the neonatal period, the newborn's and mother's blood groups (ABO; Rh) should be examined. From older children take family history and RBC osmotic fragility (OF) test (osmotic resistance decreased in hereditary spherocytosis particularly after a 24-hour incubation time) or acidified glycerol lysis time test (AGLT; shortened), or demonstrate the lack of band-3 protein by flow cytometry. Patients with congenital spherocytosis (CS) may need RBC transfusions if the haemoglobin concentration falls clearly below 80 g/l. Serum bilirubin and haptoglobin might give additional information on the degree of haemolysis. High plasma haemoglobin level, disappearance of haptoglobin binding capacity, and the presence of RBC fragments in the blood smear indicate intravascular haemolysis.
  • If there is also thrombocytopaenia, ask about intestinal symptoms and check the urine and serum creatinine for possible haemolytic uraemic syndrome.
  • If the reticulocyte count is low despite anaemia and the MCV normal or enlarged, these may be due to bone marrow hypoplasia. Check for other blood cell lines and ensure that the child does not have congenital spherocytosis (aplastic crisis usually after erythema infectiosum). Transient erythroblastopenia of childhood (TEC) is the most probable aetiology. Keep also in mind rare inborn syndromes: Diamond-Blackfan anaemia (infants) and Fanconi's anaemia (older children). Bone marrow examination is usually indicated. If leukaemia is suspected (abnormalities in other blood cell lines) refer the patient to a paediatric hospital the same day for bone marrow examination.
  • Thalassaemia minor (Thalassaemias) and haemoglobinopathies (Hb S, C, E) are examples of microcytic anaemias that do not respond to iron medication (haemoglobin concentration disproportionally high in relation to low MCV; TfR and ferritin normal or increased). Take family history, verify ethnic background, find out the child's earlier blood cell counts, examine parents' haemoglobin and MCV, and consider the examination of the child's erythrocytes (haemoglobin) with haemoglobinelectrophoresis and haemoglobin isoelectric focusing (haemoglobin fractions).

Alternative diagnoses and investigations

  • See figure (1).

References

1. Dallman PR, Siimes MA. Percentile curves for hemoglobin and red cell volume in infancy and childhood. J Pediatr 1979 Jan;94(1):26-31.  [PMID:758417]


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