Medical student teaching on haemoglobinopathies

haemoglobinopathies

1. Haemoglobinopathies Medical Student Teaching - Ellouise Bishop FY2

2. Overview Normal structure and function of haemoglobin Sickle Cell Anaemia Thalassaemia

3. Normal structure + function of haemoglobin Normal adult haemoglobin ( HbA ) is formed of: 2 alpha (α) globin chains 2 beta (β) globin chains The production of these chains is normally balanced With a ‘ haem ’ group it carries oxygen from the lungs to the bodies tissues The haemoglobin structure develops and changes in utero and after birth Foetal haemoglobin ( HbF ) contains the γ globin chain and has higher affinity for oxygen This normally gets switched to β chain at birth Understanding haemoglobinopathies - Gov.uk Sankaran, V., & Orkin, S.H. (2013). The switch from fetal to adult hemoglobin.

4. Sickle Cell Disease Autosomal recessive genetic disease = point mutation in β globin gene ( glu -> val ) Sickle Cell trait = HbAS Sickle Cell disease = HbSS Other variants include: Hb SC Hb S/beta (β0/β+) thalassaemia HbS is insoluble when deoxygenated: Causes ‘sickling’ of cells - microvascular thrombosis and organ infarction Reduced RBC lifespan leading to haemolysis = Normocytic anaemia On blood film you’ll see the sickled cells Sickle cell disease is incorporated in the NHS newborn blood spot (NBS) screening programme

5. Clinical presentations Acute Chronic Widespread painful vaso -occlusive crises Acute chest syndrome Cerebral infarction, TIA, intracranial haemorrhage Priapism Bone infarction (osteonecrosis) Osteomyelitis (Salmonella, Staphylococcus) Splenic sequestration syndrome; rarely, hepatic sequestration Aplastic crises due to parvovirus infection Chronic haemolytic anaemia and consequent cholelithiasis Chronic leg ulcers Chronic pulmonary disease and pulmonary hypertension Haematuria , proteinuria, chronic renal failure Proliferative sickle retinopathy (more common in HbSC disease) *Pregnancy: increased peripartum fetal loss, preterm births, babies small for gestational age

6. Management: acute crises Vaso-occlusive crises can occur in any tissue in the body They can be triggered by sudden changes in temperature, dehydration, hypoxia, infection General principles Effective analgesia - patients will often have their own ‘crisis plan’ and may require IV Morphine PCA Oxygen Adequate hydration Keep warm Treat underlying trigger e.g. infection if possible *Acute Chest Syndrome* Characterised by fever and/or respiratory symptoms and a new pulmonary infiltrate on chest X-Ray Investigations Bloods (FBC, U&Es), ABG Cultures (blood, sputum) CXR Management Analgesia, oxygen, fluids Incentive spirometry Appropriate tx of any infection Blood transfusion** *Get critical care involved if severe clinical features or deteriorating for consideration of ventilatory support

7. Management: long term Sickle cell patients should have regular specialist outpatient reviews and easy, direct access to specialist medical care when unwell Care under a haematologist should include: Patient education !! Prophylactic antibiotics, regular immunisations Considering hydroxycarbamide therapy Blood transfusions for relevant complications P atients with frequent crises can be candidates for regular exchange transfusions Care with administering general anaesthesia Annual transcranial doppler scans up to the age of 16 years Much of the care required by individuals with sickle cell disease is preventative and supportive care

8. Thalassaemia = group of related conditions where the amount of haemoglobin that the body produces is reduced, and this impacts on its oxygen carrying capacity One of the most common genetic conditions worldwide, affecting particular ethnic groups e.g. Microcytic hypochromic anaemia *think is degree of anaemia proportional to how microcytic the cells are? 4 main thalassemias which have clinical significance: Haemoglobin H disease α thal major β thal intermedia β thal major

9. α Thalassaemia = either reduced or absent production of alpha globin chains

10. β Thalassaemia Intermedia = β globin chain production is significantly reduced but not completely absent Major = severely reduced or absent production of the beta globin chains that make up normal adult haemoglobin, due to defective beta globin genes which are inherited from both parents This results in severe, life-threatening anaemia Management Can only be cured by bone marrow/stem cell transplant Blood transfusions Fe chelation (& avoid iron rich foods and have a daily Vit . C supplement) Splenectomy for hypersplenism Complications Untreated - failure to thrive, severe anaemia, hypersplenism , bone marrow overactivity + bone deformity, early death *Risks of regular transfusions: Excess Fe accumulation Increased risk of blood borne infections

11. Thanks for listening - Any questions?