Red Cell Aplasia ✅ Flashcards
How does red cell aplasia cause anaemia?
Due to reduced or absent red cell precursors in the bone marrow
What are the main causes of red cell aplasia in childhood?
- Diamond-Blackfan anaemia
- Transient erythroblastopenia of childhood
- Parvovirus-induced aplastic crisis
What is Diamond-Blackfan anaemia (DBA)?
A rare genetic disorder
At what age does DBA present?
Usually presents at birth or during infancy, but may present in fetal life and occasionally in older children
What is DBA associated with?
Physical abnormalities
What % of cases of DBA are associated with physical abnormalities?
- Craniofacial abnormalities
- Thumb abnormalities
- Growth restrictions
What craniofacial abnormalities are associated with DBA?
- Cleft palate
- Typical facies
What thumb abnormalities are associated with DBA?
- Hypoplastic
- Triphalangeal
What is the inheritance of DBA?
Autosomal dominant
In what % of cases of DBA is family history present?
10-20%
What mutations are involved in DBA?
Mutations in various ribosomal protein genes, the most common being RPS19
In what % of cases does a RPS19 mutation occur in DBA?
25%
What is the primary mechanism of disease in DBA?
Defective ribosomal biosynthesis, resulting in apoptosis and dysfunction in other key pathways
What function are ribosomes vital for?
Protein synthesis
What will lab tests down in DBA?
- Microcytic anaemia
- Low reticulocyte count (usually <30)
- Normal WCC
- Normal/increased platelet count
- Increased HbF
- Increased levels of eADA
What is eADA?
A RBC enzyme - erythrocyte adenosine deaminase
What is the clinical relevance of eADA?
Measurement of eADA is a useful screening test for DBA, since levels are elevated in most patients
What is done when DBA is suspected?
Bone marrow biopsy, which will confirm the diagnosis
What will be found on bone marrow biopsy in DBA?
Reduction in erythroid precursors while other cell types are unaffected
What else can be useful for the diagnosis of DBA?
Screening for ribosomal protein mutations
What treatment are most patients started on after diagnosis with DBA?
Oral prednisolone
What % of cases of DBA does oral prednisolone induce a response in?
70%
When is the commencement of steroids usually deferred until in DBA?
After initial MMR vaccination
What are the options for children with DBA where steroids are ineffective or intolerable?
Blood transfusions form the mainstay of treatment
What proportion of DBA patients are maintained on regular blood transfusions?
Around half
What can regular blood transfusions lead to in DBA?
Transfusional iron overload in the long term
What has recently become a curative option for DBA?
HSCT (haematopoietic stem cell transplantation)
What is the most common source of stem cells in HSCT for DBA?
Healthy sibling donor
What is the main differential diagnosis of DBA in neonates?
Parvovirus induced red cell aplasia
What is the main differential diagnosis of DBA in infants and young children?
Transient erythroblastopenia of childhood (TEC)
What is the median age of presentation of TEC?
2 years
What is TEC?
A rare transient red cell aplasia, thought to be triggered by an unknown infective agent
Why is it important to differentiate TEC from DBA?
As recovery occurs spontaneously in TEC, usually within 4-8 weeks, so usually no treatment is needed
What can help establish a diagnosis of TEC?
Lab tests
What are the lab features of TEC?
Anaemia In TEC is usually normocytic and associated with neutropenia in some cases. HbF and eADA are normal.
