Congenital Anaemias Flashcards
(29 cards)
What areas can be affected leading to a congenital anaemia? [3]
The red cell Membrane
Metabolic pathways
Synthesis of Haemoglobin
The main cause of Red Cell Membrane problem is…
Hereditary Spherocytosis (HS)
What is Hereditary Spherocytosis? [2]
An autosomal Dominant defect in 5 structural proteins that leads to spherical red cells
They get removed from circ by the RE system
How would someone with HS present? [3]
Neonatal presentation [1]
What picture would you expect on red cell indices[3]
What would be seen on blood film [2]
What is one presentation that can cause aplasia of red cells? [1]
Haemolytic Anaemia
- Splenomegaly & pigment gallstones
Neonatal Jaundice
- Normochromic, normocytic with high reticulocyte count
MCV low with raised MCH, MCHC
Blood film: increased osmotic fragility of RBC in hypotonic solution, anisocytosis, spherocytes
Aplastic crises precipitated by parvovirus B19 [1] causing red cell aplasia
How would we treat HS? [3]
Folic Acid
Transfusion
Splenectomy
What are defects in metabolic pathways that can lead to anaemia? [2]
Glucose 6 Phosphate Dehydrogenase (G6PD) Deficiency
Pyruvate Kinase Deficiency
G6PD: inheritance pattern
How does G6PD deficiency present? [3]
How do triggered episodes of intravascular hemolytic anemia typically present [3]
What can trigger an episode of haemolysis in G6PD deficiency? [4]
X linked, affecting males and carrying in females Neonatal Jaundice Splenomegaly Pigment Gallstones Triggered episodes of intravascular haemolytic anaemia: jaundice, anaemia & haemoglobinuria Triggers: - Broad aka fava beans - Infection - Drugs: - Henna
What drug groups can trigger intravascular hemolysis episode resulting in anemia in a G6PD deficient patient? [6]
Lab workup:
Appearance on peripheral blood film for G6PD [1]
When should you perform an enzyme assay and why should you not do test during a crisis? [2]
Antimalarials, sulphonamides, nitrofurantoin (ab), aspirin, antihelminthics & Vit K analogues
Blister or bite cells
8 weeks after crisis
Young RBCs may have enough enzyme giving false negative result
There are 2 categories of condition affecting your haemoglobin:
Features of both blood films are the same - name 2 features
Thalassaemias = mutation –> absent globin chains
Haemoglobinopathies e.g. Sickle Cell = structurally abnormal globin chains
Both feature hypochromic, microcytic anaemia
What are the major types of Thalassaemias? [4]
Homozygous Thalassaemia (Alpha Zero) - No alpha chains
Homozygous Beta Thalassaemia Major = No Beta chains
Thalassemia Intermedia = Non-transfusion dependant Thalassaemias
Thalassaemia Minor = Carrier State - hypo chromic, microcytic blood film
Beta thalassemia major:
Typical presentation age [1]
Beta thalassemia major causes severe anemia. What are the complications of this? [4]
Life expectancy [1]
3-6 months Severe anemia causes: - Expansion of ineffective bone marrow - Causing bony deformities - Splenomegaly - Growth retardation Life expectancy: untreated w irregular transfusions <10y
Beta thalassemia major:
Treatment [4]
Risk of chronic transfusion support [2]
Treatment:
- 4-6 wkly transfusions
- Plus Iron Chelation therapy (desferrioxamine)
- Vitamin C (promote urinary iron excretion)
- Bone Marrow Transplant - curative
To prevent iron overload from the transfusions
Iron overloading can lead to heart, liver, endocrine failure if untreated
How is Sickle Cell Disease inherited? [1]
Composition of sickle hemoglobin (HbS): haem molecule + [2] + [2]
Explain HbS polymerization and how this causes problems in sickle cell disease [1]
If sickling is a reversible process, explain why sickled red cells are more likely to be hemolysed? [2]
Autosomal Recessive
Composition of sickle hemoglobin (HbS): haem molecule + 2 alpha chains + 2 beta/sickle chains
HbS molecules form long polymers which distort red cell into a sickle shape [1]
Sickling is initially reversible but the damage caused by repeated polymerization is cumulative [1] and eventually leads to dehydration [1] of red cell and red cell injury > hemolysis
Pathogenesis of vaso-occlusion from hemolysis in Sickle cell anemia? [5]
Hemolysis due to abnormal shape of cells
Endothelial activation and pro-inflammatory factors
Coagulation activation
Dysregulation of vasomotor tone of vasodilator mediators eg NO
Leading to vaso-occlusion
What are the major problems that sickle cell causes?
- Vaso-occlusive tissue damage causing pain crises [3]
- Chronic hemolytic anemia [2]
- Spleen related complications [1]
Vaso-occlusive tissue damage complications > pain crises:
- Stroke due to cerebral vasculopathy
- Acute chest syndrome, pulmonary htn caused by pulmonary vasculopathy
- Aseptic bone necrosis, osteomyelitis
Chronic hemolytic anemia complications:
- Gall stones
- Aplastic crisis
Spleen related complications
- Initial hypersplenism then splenic atrophy occurs
- Hyposplenism –> high infection risk
How do you treat a Sickle cell patient with a Painful Vaso-occlusive crisis? [3]
What is one analgesia that cannot be used in sickle patients and why? [2]
Opiates, NSAIDs
O2, hydration
Abx if infected
No pethidine as risk of epileptic seizures
How would a Chest crisis present in sickle cell? [3]
What can be seen on CXR?
Chest pain, fever & worsening hypoxia
Plus infiltrates visible on CXR
How do we treat a chest-crisis in sickle cell? [5]
Resp support O2, IV Fluids Analgesia Abx: cephalosporin, macrolide Transfusion Bronchodilators
What can we give sickle cell patients as prophylaxis? [3]
Pneumococcal vaccine
Penicillin & Anti-malarials (again inf)
Folic Acid (reduce anaemia)
What treatments can we give for the chronic management of Sickle Cell Disease (not the acute events)? [5]
o Folate: as due to decreased RBC lifespan folate often depleted
o HYDROXYCARBAMIDE: for frequent crises
o Bone marrow transplantation (curative)
o Immunisation
o Prophylactic antibiotics: PHENOXYMETHYLPENICILLIN
What’s cool about a G6PD deficiency?
It protects you against malaria so it’s much more common in those parts of the world
What do defects in haem synthesis cause? [2]
In mitochondrial part –> Sideroblastic anaemia
In the cytoplasmic part –> Porphyrias
Sideroblastic anemia - blood film features [2]
Level of ferritin you would expect to see [2]
What defect in haem synthesis is involved?
Give 2 causes of sideroblastic anemia (aetiology): congenital and acquired
Inheritance pattern
Mx [3]
Basophilic stippling, microcytic anemia Normal or high ferritin Mitochondrial steps of haem synthesis ALA synthase mutations, acquired myelodysplasia X-linked recessive
Mx: mx of underlying cause, PYROXIDINE +/- repeated transfusion for severe anaemia
Enzyme metabolic pathway defects Pyruvate Kinase Deficiency Underlying pathology [3] Pattern of inheritance [1] Tx [1]
Reduced ATP, increased 2,3-DPG, rigid cells
Autosomal recessive
Splenectomy
