Common paediatric anaemias Flashcards
Scenario 1
A 1 year old boy, breast fed from birth is noted to be pale at the GP surgery. Mum and Dad are vegans and wish the child to be brought up to enjoy a similar diet.
The following blood results are obtained:
Hb 70 g/L
MCV 60 fl
WBC 6 x 109/l
Platelets 550 x 109/l
Ferritin 5 µg/l
● Identify the abnormalities from the laboratory tests.
Microcytic anaemia
Thrombocytosis
Low serum ferritin
What is a differential diagnosis?
Iron deficiency anaemia (really only one because serum ferritin is really low)
● What are the likely underlying pathophysiological mechanisms producing these abnormalities? (why are the cells small)
Failure to produce Hb as a lack of iron - cells continue to divide as no problem with machinery of cell division
As cells divide, progeny get smaller, as Hb not accumulating in the cytoplasm cells keep dividing so more divisions and progeny ends up being smaller (microcytic)
What is the likely cause?
Iron deficiency secondary to insufficient dietary intake
As getting bigger, iron intake from milk is now insufficient for needs whereas it was sufficient 6 months before
Describe how pregnancy can cause iron deficient anemia
Not iron deficient on the same diet pre-pregnancy, but with increased iron demands of pregnancy, may now become iron deficient so a big drive for giving iron in pregnancy at an early stage if any evidence of iron deficiency
● How would you treat this anaemia and what would be the mechanism of action of this treatment.
Sodium feredetate (will correct anaemia quicker) and also education to change diet (both correct)
How would you monitor if the treatment was effective?
Could check bloods but clinical assessment (pallor, activity, growth) all important especially in developing child
Identify the abnormalities from the laboratory tests.
Microcytic anaemia
High ferritin
● What are the likely underlying pathophysiological mechanisms producing these abnormalities?
Mechanism failure of globin synthesis (not iron deficiency)
Clinical timing and history point towards beta thalassaemia. In utero, the predominant Hb is HbF (alpha2gamma2) and switching occurs towards birth to HbA (alpha2beta2)
In beta thalassaemia, cannot make beta chains so can’t make HbA so Hb will fall as time goes by and iron of the now recycled fetal red cells ends up in store
● Which further laboratory investigations are necessary and explain what pathophysiological mechanisms they are measuring.
HPLC (High performance liquid chromatography)
This has replaced Hb electrophoresis for assessing the different types of Hb (HbA, HbA2, HbF, HbS, etc.)
What are the likely underlying pathophysiological mechanisms producing these abnormalities? Why are cells small?
Not iron deficient, but issue with globin chains
Hb does not get made and so does not accumulate in precursors. Slightly more complex as the subunit that is made (in beta thalassaemia major that is alpha subunits) will accumulate and is toxic to cells as they precipitate and cause premature death i.e. intramedullary haemolysis but there is not a reticulocyte response obviously as reticulocytes cannot be made
An ineffective and hyper plastic marrow is the result, and the cause of much of the pathophysiology
How would you treat this anaemia and what would be the mechanism of action of this treatment.
Regular transfusion to maintain a minimum Hb is mainstay management
If Hb is not allowed to dip too low then this will prevent hypoxia sensor being triggered to stimulate erythropoeisis and will switch off the ineffective and hyper plastic marrow
Cuts down on wasted energy, limits attempts at extra medullary haumatopoeisis and stops the expansion of bone marrow cavities
What are complications of blood transfusion in beta thalassaemia major?
Iron overload (organ damage, especially liver and heart)
Infection transmission e.g. viral (Very rare nowadays)
Allo antibody formation making crossmatch difficult (circa 30% get alloantibodies especially if racial mismatch from donors)
Poor venous access
Poor quality of life from regular hospital attendance
How do we manage iron overload?
Iron chelation
● How would you monitor if the treatment was effective?
Aim is to stop ineffective erythropoeisis which uses energy and consequences of marrow expansion such as bone disease, splenomegaly and infections
Monitor growth and development (secondary development related to bone age), performance at school, exercise tolerance, evidence of erythroid hyperplasia (want to avoid) e.g. splenomegaly
Monitor iron overload and response to chelation (T2 MRI scan of liver and heart)
Regular ferritins
Identify the abnormalities from the laboratory tests.
Normocytic anaemia
Thrombocytosis
Hyperbilirubinemia
Polychromasia
Spherocytosis
● What are the likely underlying pathophysiological mechanisms producing these abnormalities?
Jaundiced because increased peripheral destruction of red cells and this is an excess of a normal RBC breakdown product (reticulocytosis)
● What is a differential diagnosis?
Congenital problems (clue in the history); other causes of spherocytosis include autoimmune haemolysis, burns, recent transfusion (transfused cells have been in storage and look a bit odd in first few days), splenectomy (spherocytes can occur normally but are rapidly cleared by a functioning spleen, haemolytic disease of the newborn (if mum / baby ABO mismatch))
● Which further laboratory investigations are necessary and explain what pathophysiological mechanisms they are measuring.
Don’t need a test to confirm clinical family history, and film in keeping with the diagnosis
Specialist tests if in doubt - EMA binding (an immunophenotyping test where the molecule binds to the band 3 complex and fluoresces) cryohaemolysis test, or SDS PAGE analysis (run membrane proteins on an electrophoresis gel and see if any of them run abnormally implying they are mutated / abnormal, genetic tests rarely performed)
● How would you treat this anaemia and what would be the mechanism of action of this treatment.
Folic acid as increased RBC turnover (erythroid hyperplasia)
Splenectomy can be considered (and sometimes cholecystectomy because prone to gallstones) if it is felt that delays growth/development or needing transfusions/symptomatic from anaemia
NB: Age considerations >6 generally as splenectomy gives increased infection risk which is more marked in the very young (hence need for vaccination and prophylactic antibiotics)
Splenectomy results in more prolonged red cell survival and can result in improvement in anaemia
