Haemoglobinopathies Flashcards
What are Haemoglobinopathies?
Pathologies of haemoglobin structure
What are the 2 categories of Haemaglobinopathies?
- Thalassaemia
- Sickle Cell Anaemia
What is the normal haemoglobin structure?
- Haem group consisting of 4 chains
- 2 alpha chains and 2 beta chains
What is the point mutation that causes Sickle Cell Anaemia?
- Substitution of amino acid glutamic acid with Valine
- Occurs in B globin chain
- If both genes coding for the chain are affected, then the disease develops
- AUTOSOMAL RECESSIVE
What is the pathophysiology of Sickle Cell Anaemia?
- Abnormal chain polymerises when deoxygenated
- Polymerisation causes development of abnormal sickle shape
- Deformed RBCs are fragile and undergo haemolysis, blocking small vessels
- Blockage leads to infarction
- Haemoglobin release and NO consumption results in vasoconstriction and endothelial dysfunction (pulmonary hypertension)
What are the clinical features of Sickle Cell Anaemia?
- Vaso-occlusive painful crisis
- Aplastic crisis
- Sequestraiton crisis
What are the emergency events to watch out for in Sickle Cell Anaemia?
- Thrombotic crisis (vaso-occlusive)
- Sequestration crisis
- Acute chest syndrome
- Aplastic crisis
- Haemolytic crisis
What is sequestration?
- Pooling of blood in the spleen and liver causing organmegaly
What are the investigations in suspected Sickle Cell Anaemia?
=> Bloods
- Hb low
- Bilirubin high
- Reticulocyte count high
=> Sickle Solubility Test - comes back +ve
=> Hb electropheresis - main diagnostic test
What is the management of Sickle cell Disease?
- Hydroxycarbimide
- Prophylactic antibiotics as splenic infarction leads patient immunocompromised
- Bone Marrow Transplant
What is the emergency management of Crisis?
- Prompt analgesia
- Crossmatch blood
- Do septic screen
- Rehydrate and keep warm
- Blood transfusion if Hb and reticulocytes drop massively
- Exchange transfusion if condition worsening
- Haematology referral
=> Long term management:
- Hydroxyurea
- Pneumococcal vaccine every 5 years
What are the 2 main types of Thallassaemia and what is it?
- alpha thallassaemia
- B thallassaemia
Thallassaemia is when the proportions of alpha and beta chains (1:1) change, due to underproduction of one of these chains leading to precipitation
=> This can cause:
- cell damage
- death of RBCs precursors
What is alpha-thallassaemia?
- Reduced alpha chain synthesis
- This chain is coded for by 4 genes
=> Deleted genes: 1 deleted gene = Normal 2 deleted genes = Carrier 3 deleted genes = DISEASE - hypochromic microcytic anaemia 4 deleted genes = death utero
How does B-thallassaemia occur?
- Caused by point mutation on chromosome 11
- Leads to decreased production of B chain or complete absence
- 3 main types of B-thallassaemia
What are the 3 main types of B-thallassaemia?
=> B thallassaemia Minor
- Asymptomatic Heterezygous carrier state
- Mild or no anaemia
- Low MCV and MCH
- Present confused and iron deficiency anaemia
=> B thallassaemia Intermedia
- Moderate anaemia but do need blood transfusion
- Symptoms: gallstones, leg ulcers, splenomegaly
=> B thallassaemia Major:
- Significant abnormalities in all B globin chains
- First year of life = failure to thrive + hepatosplenomegaly
- Osteopenia
- Bone marrow hypertrophy
