CHILDHOOD ANAEMIA Flashcards
What is the main site of haematopoiesis in the fetus?
Liver
What is the main Hb in fetal life? What are the components (in terms of chains)?
HbF
2 alpha chains
2 gamma chains
By what stage of life should HbF levels be very low if not undetectable?
By 1 year of age HbF levels should be very low and increased proportions of HbF are a sensitive indicator of some inherited disorders of haemoglobin production.
What is the average Hb level of the neonate at birth?
14-21.5 g/dL
What happens to Hb levels after birth?
There is quite a sharp decline reaching a nadir at 2 months.
What is the normal range of the Hb levels at 2 months of age?
Between 9 and 13 g/dL
What might cause a baby to have a steeper fall in Hb over the first few weeks/months of life?
Premature babies fall to a mean Hb value of 6.5 - 9 g/dL over about 4-8 weeks
What is the normal white cell count in neonates?
Higher than older children – 10-25 x 10^9/L
What is the normal platelet count in neonates?
Same as adult range – 150-400 x 10^9/L
What is the definition of anaemia in neonates?
Hb less than 14 g/dL
What is the definition of anaemia in infants?
Hb less than 10 g/dL
What is the definition of anaemia in children?
Hb less than 11 g/dL
At what Hb levels will an anaemic infant become symptomatic?
Below 6-7 g/dL
What are the infant and young children specific signs of anaemia?
Feeding more slowly than usual
‘Pica’ - eating of non-food materials such as soil, chalk and gravel.
Reduced concentration and intellectual function
What are the three overarching categories for causes of anaemia?
Impaired red cell production
Increased red cell destruction (haemolysis)
Blood loss
Reduced red cell production may be due to: ineffective erythropoiesis or red cell aplasia. What is the difference?
Ineffective erythropoiesis: red cell production occurs at a normal or even increased rate but differentiation or survival of the red cells in defective
Red cell aplasia: complete absence of red cell production
What are the causes of impaired red cell production through ineffective erythropoiesis in a child?
Iron deficiency
Folic acid deficiency
Chronic inflammation (juvenile idiopathic arthritis)
Chronic renal failure
Myelodysplasia
What are the causes of impaired red cell production through red cell aplasia in a child?
Parvovirus B19
Diamond-Blackfan anaemia
Fanconi anaemia
Aplastic anaemia
Leukaemia
What are the diagnostic clues to ineffective erythropoiesis being the cause of anaemia in a child?
Normal reticulocyte count
Abnormal MCV - low in iron deficiency, raised in folic acid deficiency
What are the three main causes of iron deficiency in children?
Inadequate intake
Malabsorption
Blood loss
What is the iron requirement of an infant?
8 mg/day (about the same as a grown man)
What are the sources of iron for a 1 year old infant?
Breast milk - low content but up to 50% is absorbed
Infant formula - supplemented with iron
Cow’s milk - higher content but only 10% is absorbed
Solids introduced at weaning - eg cereals. High iron but only 1% is absorbed
What are the diagnostic clues of iron deficiency being the cause of anaemia in a child?
Microcytic, hypochromic anaemia
Low serum ferritin
What are the main causes of microcytic anaemia in a child?
Iron deficiency anaemia
Beta-thalassaemia trait
Alpha-thalassaemia trait
Anaemia of chronic disease
How do we manage a child with iron deficiency anaemia?
Dietary advice - eg stop giving so much cow’s milk
Supplementation with oral iron
What are the best tolerated iron supplement preparations for children?
Sytron - sodium iron edetate
Niferex - polysaccharide iron complex
How long should iron supplementation be continued for in a child with iron deficiency anaemia?
Until Hb is normal and then for 3 more months
At what rate should the Hb rise with iron supplementation?
1 g/dL per week
What are the main causes of chronic blood loss in children leading to iron deficiency anaemia?
Nose bleeds
Meckel’s diverticulum
Bleeding disorders such as von Willebrand disease
What are the main causes of iron malabsorption in children leading to iron deficiency anaemia?
Coeliac disease
When do we treat iron deficiency anaemia in children with blood transfusion?
Never - even an Hb of 2-3 g/dL can be corrected with iron supplmentation
What are the diagnostic clues to red cell aplasia being the cause of anaemia in a child?
Low reticulocyte count despite low Hb
Normal bilirubin
Negative direct antiglobulin test (Coombs test)
Absent red cell precursors on bone marrow examination
At what age do most cases of Diamond-Blackfan present with anaemia?
2-3 months, but 25% present at birth
As well as anaemia, what are the features associated with Diamond-Blackfan anaemia?
Short stature
Abnormal thumbs
How do we treat Diamond-Blackfan anaemia?
1st line - Oral steroids
2nd line - Blood transfusions given to those who steroid unresponsive
3rd line - may be offered stem cell transplantation
What is the condition that has the same haematological features as Diamond-Blackfan anaemia but is not a genetic disease and is usually triggered by viral infection?
Transient erythroblastopenia of childhood (TEC) - child will usually recover in a matter of weeks
What are causes of increased red cell destruction leading to anaemia in a child?
Red cell membrane disorders - Hereditary spherocytosis
Red cell enzyme disorders - Glucose-6-phosphate dehydrogenase deficiency
Haemoglobinopathies - Thalassaemias, sickle cell disease - SEE HAEMATOLOGY SLIDES
Immune - haemolytic disease of the newborn, automimmune haemolytic anaemia
What is the usual lifespan of a red blood cell?
120 days
What are the features of increased haemolysis in a child?
Anaemia
Jaundice
Hepatomegaly and splenomegaly
What are the diagnostic clues to excessive haemolysis being the cause of anaemia in a child?
Raised reticulocyte count - polychromasia on the blood film, with red cells having a lilac colour
Unconjugated bilirubinaemia and increased urinary urobilinogen
Abnormal appearance of red cells on blood films - spherocytes, sickle shaped or very hypochromic
Positive direct antiglobulin test
Increased red blood cell precursors in the bone marrow.
What is the inheritance pattern of hereditary spherocytosis?
Autosomal dominant, however in 25% there is no family history and it is therefore caused by new mutation
What are the three main protein of the red cell membrane affected in hereditary sperocytosis?
Spectrin
Ankyrin
Band 3
Why does hereditary spherocytosis lead to the characteristic spheroidal red cells?
Problems with protein in the cell membrane leads to the red cell losing part of its membrane as it passes through the spleen. This reduction in surface to volume ratio leads to a spheroidal shape. This renders them less deformable than normal red cells and hence the spleen destroys them.
What are the clinical features of hereditary spherocytosis?
Failure to thrive
Jaundice - usually during childhood but can be as early as first few days of life
Anaemia - presents in childhood with mild anaemia (9-11 g/dL). Can fall further in infection
Mild to moderate splenomegaly
Aplastic crisis - uncommon, transient (usually lasting 4-6 weeks). Most often precipitated by Parvovirus B19
Gallstones - due to increased bilirubin excretion
How is hereditary spherocytosis normally diagnosed?
Blood film is usually diagnostic.
Need to exclude autoimmune haemolytic anaemia as this also causes spherocytes on blood film
Can also be confirmed by osmotic fragility test
How do we manage a child with hereditary spherocytosis?
Most children have mild anaemia and only require folic acid supplementation
With more severe symptoms, splenectomy may be indicated
At what age is splenectomy usually carried in a child with hereditary spherocytosis?
After 7 years of age
What must be checked before splenectomy in a child with hereditary spherocytosis?
Vaccinated against - H. influenzae, meningitis C and S. pneumonia
Also lifelong oral penicillin is often prescribed
How do we manage a child with hereditary spherocytosis who suffers an aplastic crisis?
One or two blood transfusions will normally be required over 3-4 week period
People from which parts of the world are most affected by G6PD deficiency?
Central Africa
The Mediterranean
Middle East
Far East
What is the G6PD enzyme used for in the red cell?
Preventing oxidative damage
What is the inheritance pattern of G6PD deficiency?
X-linked recessive
What are the clinical features of G6PD deficiency?
Neonatal jaundice - usually in the first 3 days of life
Acute haemolysis precipitated by a number of factors accompanied by:
Fever
Malaise
Dark urine
What are the factors that can precipitate acute haemolysis in a individual with G6PD deficiency?
Infetion
Certain drugs
Fava beans (broad beans)
Napthlene in mothballs
What are the drugs that can precipitate acute haemolysis in a individual with G6PD deficiency?
Antimalarials:
Primaquine
Quinine
Chloroquine
Antibiotics:
Sulphonamides - co-trimoxazole
Quinolones - ciprofloxacin, nalidixic acid
Nitrofurantoin
Analgesics:
High dose aspirin
What levels of Hb are reached during acute haemolysis associated with G6PD deficiency?
Below 5 g/dL over 24-48 hours - so very quick drop
How do we confirm diagnosis of G6PD deficiency?
Measure G6PD activity in RBCs
NB - during a crisis may be misleadingly elevated as high levels in reticulocytes, so need to remeasure in steady state
How do we manage children with G6PD deficiency?
There is no specific treatment, other than avoiding known triggers.
In the acute phase of hemolysis, blood transfusions might be necessary, or even dialysis in acute kidney failure. Blood transfusion is an important symptomatic measure, as the transfused red cells are generally not G6PD deficient and will live a normal lifespan in the recipient’s circulation.
What are the clinical features of sickle cell disease?
Chronic anaemia
Acute anaemia - haemolytic crisis, aplastic crisis, sequestration crisis
Increased risk of infection
Painful vaso-occlusive
Priapism
Splenomegaly
What precipitates a haemolytic crisis in someone with sickle cell disease?
Infection
What precipitates an aplastic crisis in someone with sickle cell disease?
Parvovirus B19
What are the features of sequestration crisis?
Sudden splenic or hepatic enlargement
Abdominal pain
Circulatory collapse from accumulation of sickled cells in spleen
Why are sickle cell patients more at risk of infection?
Hyposplenism secondary to chronic sickling and microinfarction
What proportion of children with sickle cell disease will have a stroke?
1 in 10.
An even higher proportion will have more subtle neurological damage
What are the sites more commonly affected by a painful sickle crisis?
Bones of limb and spine
What is hand-foot syndrome a common mode of sickle cell presentation in late infancy?
Painful dactylitis (swelling of fingers and feet) due to vaso-occlusion.
What is the most serious type of sickle cell vaso-occlusive crisis?
Acute chest syndrome
How do we treat acute chest syndrome of sickle cell disease?
CPAP
Exchange transfusion
Broad-spectrum antibiotics
What are the long-term complications of sickle cell disease?
Short stature
Delayed puberty
Stroke and cognitive problems
Adenotonsillar hypertrophy - causing sleep apnoea
Cardiac enlargement and heart failure
Renal dysfunction
Pigment gallstones
Leg ulcers
Psychosocial problems from missing school
