Congenital Anaemias Flashcards
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
Aplastic anaemia
Name 3 congenital causes
Name 5 acquired causes
Mx [2]
- Congenital:
o Fanconi: Ashkenazi Jews, short and pigmented
o Dyskeratosis congenital: premature ageing
o Swachman-Diamond syndrome: pancreatic exocrine dysfunction - Acquired: drugs, viruses (parvovirus, hepatitis) or occupational exposure, ALL, pregnancy
Mx: transfusions, allogeneic bone marrow transplant
What drugs increase risk of developing AA?
What occupational exposure increases risk?
- Drugs: chloramphenicol, chloroquine, penicillamine.
- Occupational exposure: benzene, pesticides.
Most of the management for Aplastic Anaemia is supportive, what treatments are reserved for severe/very severe AA:
◆ In patients aged <40 years with a matched sibling, BMT is first line treatment.
◆ Patients aged <40 years with no matched sibling are given immunosuppressive therapy with ATG and ciclosporin as first-line treatment.
Pure red cell aplasia
Name 6 acquired causes
- an isolated marked reduction or absence of erythroid activity in the bone marrow. The other cell lineages remain unaffected.
Acquired causes - Viral illness such as parvovirus B9 or EBV. More common in patients with an existing red cell disorder, such as sickle cell anaemia.
- Drugs including azathioprine and co-trimoxazole.
- Autoimmune conditions such as rheumatoid arthritis and SLE.
- Thymomas.
- CLL.
- Anti-erythropoietin antibodies secondary to erythropoietin injections in chronic renal failure patie
If PRCA is congenital i.e., presenting in childhood, what is the natural course of disease and treatment?
In children, PRCA is usually transient and self-limiting, and management is often expectant, unless a red cell trans- fusion is clinically indicated. Specific treatments are avoided if possible to minimise complications.
