Anaemia is defined as a low level of haemoglobin in the blood. This is the result of an underlying disease and is not a disease itself. The prefix an- means without and the suffix -aemia refers to blood.
Haemoglobin is a protein found in red blood cells. It is responsible for picking up oxygen in the lungs and transporting it to the cells of the body. Iron is an essential ingredient in creating haemoglobin and forms part of the structure of the molecule. When a patient has a low level of haemoglobin, they have a condition called anaemia.
You can diagnose a patient with anaemia when they have a low haemoglobin. When you find an anaemic patient you should check the mean cell volume (MCV). This is the size of the red blood cells, which can give an indication of the underlying cause.
The normal ranges for haemoglobin are determined by the local haematology lab. This will depend on the age of the child. This varies significant for the first 6 months as the child transitions from fetal to adult haemoglobin and adapts to taking oxygen from the air rather than the placenta. The normal values are different for males and females after puberty, due to menstruation and regularly blood loss in females. A rough guide to what the normal values is included below. This should not be used as a reference, and is simply to give an impression of how the levels change with age:
150 – 235 grams/litre
2 – 4 weeks
135 – 190 grams/litre
4 – 8 weeks
95 – 130 grams/litre
2 months – 6 years
110 – 140 grams/litre
6 – 12 years
115 – 155 grams/litre
Female age 12 – 18
120 – 160 grams/litre
Male aged 12 – 18
130 -160 grams/litre
Causes of Anaemia In Infancy
Physiologic anaemia of infancy causes most cases of anaemia in infancy.
The other causes of anaemia in infants are:
- Anaemia of prematurity
- Blood loss
- Twin-twin transfusion, where blood is unequally distributed between twins that share a placenta
Haemolysis is a common cause of anaemia in infancy. There are a number of causes of haemolysis in a neonate:
- Haemolytic disease of the newborn (ABO or rhesus incompatibility)
- Hereditary spherocytosis
- G6PD deficiency
Physiologic Anaemia of Infancy
There is a normal dip in haemoglobin around six to nine weeks of age in healthy term babies. High oxygen delivery to the tissues caused by the high haemoglobin levels at birth cause negative feedback. Production of erythropoietin by the kidneys is suppressed and subsequently there is reduced production of haemoglobin by the bone marrow. The high oxygen results in lower haemoglobin production.
Anaemia of Prematurity
Premature neonates are much more likely to become significantly anaemic during the first few weeks of life compared with term infants. The more premature the infant, the more likely they are to require one or more transfusions for anaemia. This becomes more likely if they are unwell at birth, particularly with neonatal sepsis.
Premature neonates become anaemic for a number of reasons:
- Less time in utero receiving iron from the mother
- Red blood cell creation cannot keep up with the rapid growth in the first few weeks
- Reduced erythropoietin levels
- Blood tests remove a significant portion of their circulating volume
Haemolytic Disease of the Newborn
Haemolytic disease of the newborn is a cause haemolysis (red blood cells breaking down) and jaundice in the neonate. It is caused by incompatibility between the rhesus antigens on the surface of the red blood cells of the mother and fetus. The rhesus antigens on the red blood cells vary between individual. This is different to the ABO blood group system.
Within the rhesus group, there are many different types of antigens that can be present or absent depending on the person’s blood type. The most important antigen within the rhesus blood group system is the rhesus D antigen.
When a woman that is rhesus D negative (does not have the rhesus D antigen) becomes pregnant, we have to consider the possibility that the fetus will be rhesus D positive (has the rhesus D antigen). It is likely at some point in the pregnancy the blood from the fetus will find a way into her bloodstream. When this happens, the fetal red blood cells display the rhesus D antigen. The mother’s immune system will recognise the rhesus D antigen as foreign and produce antibodies to the rhesus D antigen. The mother has then become sensitised to rhesus D antigens.
Usually, this sensitisation process does not cause problems during the first pregnancy (unless the sensitisation happens early on, such as during antepartum haemorrhage). During subsequent pregnancies, the mothers anti-D antibodies can cross the placenta into the fetus. If that fetus is rhesus positive, these antibodies attach themselves to the red blood cells of the fetus and causes the immune system of the fetus to attack its own red blood cells. This leads to haemolysis, causing anaemia and high bilirubin levels. This leads to a condition called haemolytic disease of the newborn.
A direct Coombs test (DCT) can be used to check for immune haemolytic anaemia. This will be positive in haemolytic disease of the newborn.
Causes of Anaemia in Older Children
The key causes of anaemia in older children are:
- Iron deficiency anaemia secondary to dietary insufficiency. This is the most common cause overall.
- Blood loss, most frequently from menstruation in older girls
Rarer causes of anaemia in children include:
- Sickle cell anaemia
- Hereditary spherocytosis
- Hereditary eliptocytosis
- Sideroblastic anaemia
Worldwide, a common cause of blood loss causing chronic anaemia and iron deficiency is helminth infection, with roundworms, hookworms or whipworms. This can be very common in developing countries and those living in poverty. It is more unusual in the UK. Treatment is with a single dose of albendazole or mebendazole.
Anaemia is initially subdivided into three main categories based on the size of the red blood cell (the MCV). These have different underlying causes:
- Microcytic anaemia (low MCV indicating small RBCs)
- Normocytic anaemia (normal MCV indicating normal sized RBCs)
- Macrocytic anaemia (large MCV indicating large RBCs)
Causes of Microcytic Anaemia
A helpful mnemonic for understanding the causes of microcytic anaemia is TAILS.
- T – Thalassaemia
- A – Anaemia of chronic disease
- I – Iron deficiency anaemia
- L – Lead poisoning
- S – Sideroblastic anaemia
Causes of Normocytic Anaemia
There are 3 As and 2 Hs for normocytic anaemia:
- A – Acute blood loss
- A – Anaemia of Chronic Disease
- A – Aplastic Anaemia
- H – Haemolytic Anaemia
- H – Hypothyroidism
Causes of Macrocytic Anaemia
Macrocytic anaemia can be megaloblastic or normoblastic. Megaloblastic anaemia is the result of impaired DNA synthesis preventing the cell from dividing normally. Rather than dividing it keeps growing into a large, abnormal cell. This is caused by a vitamin deficiency.
Megaloblastic anaemia is caused by:
- B12 deficiency
- Folate deficiency
Normoblastic macrocytic anaemia is caused by:
- Reticulocytosis (usually from haemolytic anaemia or blood loss)
- Liver disease
- Drugs such as azathioprine
Symptoms of Anaemia
There are many generic symptoms of anaemia:
- Shortness of breath
- Worsening of other conditions
There are symptoms specific to iron deficiency anaemia:
- Pica describes dietary cravings for abnormal things such as dirt and can signify iron deficiency
- Hair loss can indicate iron deficiency anaemia
Signs of Anaemia
Generic signs of anaemia:
- Pale skin
- Conjunctival pallor
- Raised respiratory rate
Signs of specific causes of anaemia:
- Koilonychia refers to spoon shaped nails, which can indicate iron deficiency
- Angular chelitis can indicate iron deficiency
- Atrophic glossitis is a smooth tongue due to atrophy of the papillae and can indicate iron deficiency
- Brittle hair and nails can indicate iron deficiency
- Jaundice occurs in haemolytic anaemia
- Bone deformities occur in thalassaemia
- Full blood count for haemoglobin and MCV
- Blood film
- Reticulocyte count
- Ferritin (low iron deficiency)
- B12 and folate
- Bilirubin (raised in haemolysis)
- Direct Coombs test (autoimmune haemolytic anaemia)
- Haemoglobin electrophoresis (haemoglobinopathies)
Reticulocytes are immature red blood cells. A high level of reticulocytes in the blood indicates active production of red blood cells to replace lost cells. This usually indicates the anaemia is due to haemolysis or blood loss.
Further investigation will depend on the suspected underlying cause.
Management depends on establishing the underlying cause and directing treatment accordingly. Iron deficiency can be treated with iron supplementation. Severe anaemia may require blood transfusions.
Last updated January 2020