Aims and objectives • Why is haematology so difficult? • Classification of anaemias • Duration: 70 mins • Slides and recordings: app.bitemedicine.com 2
Case-based discussion: 1 History and examination A 20-year-old lady presents to the GP with lethargy. She is a medical student and complains of intense fatigue, struggling to stay awake during lectures. As soon as she gets home, she goes straight to bed. She reveals that she often has heavy periods. Observations HR 80, BP 118/77, RR 18, SpO2 98%, Temp 37.0 3
Question 1 A 20-year-old lady presents to the GP with lethargy. She is a medical student and complains of intense fatigue, struggling to stay awake during lectures. As soon as she gets home, she goes straight to bed. She reveals that she often has heavy periods. Observations: HR 80, BP 118/77, RR 18, SpO2 98%, Temp 37.0 Q1 Q2 Q3 Q5 Q4 Which of the following is the most likely type of anaemia? Microcytic Normocytic Macrocytic Megaloblastic Aplastic app.bitemedicine.com 4
Explanations Q1 Q2 Q3 Q4 Q5 Which of the following is the most likely type of anaemia? Microcytic Chronic blood loss, e.g. menstrual bleeding, leads to iron deficiency and is the commonest cause of anaemia worldwide Normocytic Iron deficiency is microcytic Macrocytic Iron deficiency is microcytic Megaloblastic This is a subtype of macrocytic anaemia Aplastic This is a cause of a normocytic anaemia and may occur secondary to infection e.g. parvovirus B19 app.bitemedicine.com 5
Introduction: Anaemia Structure of haemoglobin 4 polypeptide ‘globin’ chains • Each chain is complexed to a haem molecule • Haem is an iron containing compound • Anaemia: reduction of haem and/or globin Normal Hb variants Structure Proportion in adults HbA α 2 β 2 90% HbA 2 α 2 δ 2 <2% HbF <2-5% α 2 γ 2 6
Introduction: Anaemia Anaemia Men: Hb <130g/L • Women: Hb <120g/L • Classified based on mean corpuscular volume (MCV) • Microcytic (MCV < 80fL) Normocytic (MCV 80-95fL) Macrocytic (MCV >95fL) Iron deficiency Acute blood loss B12 deficiency Thalassaemia Haemolytic anaemia Folate deficiency Anaemia of chronic disease Alcohol Anaemia of chronic disease Sideroblastic anaemia Liver disease Chronic kidney disease Hypothyroidism Aplastic anaemia 7
Clinical features: General principles Symptoms Signs Fatigue Tachycardia SOB on exertion Tachypnoea Chest pain Hypotension Palpitations Pallor 8
History taking: General principles History of presenting complaint Symptoms of anaemia e.g. SOB • Screen for areas of blood loss: GI, resp, urinary tract, menstrual • Alarm symptoms: weight loss, loss of appetite, night sweats, lymphadenopathy • Dietary habit • Past medical history Chronic disease • Trauma • Family history Inherited disorders e.g. haemoglobinopathies • Drug history, social history 9
Investigations: General principles Bedside Full set of observations • Bloods FBC: reduced Hb. Assess MCV • Blood film • Iron studies • B12 and folate levels • Haemolysis screen: bilirubin, haptoglobin, Coombs test • U&Es: CKD • TFTs: hypothyroidism • LFTs: chronic liver disease • Imaging Assess for site of blood loss • Special tests Bone marrow biopsy • 10
Iron deficiency anaemia Definition: reduced intake, increased requirement, or increased Microcytic anaemia loss of iron, leading to anaemia Iron deficiency Epidemiology: Thalassaemia Most common cause of anaemia and affects ~ 500 million • people worldwide (NICE) Anaemia of chronic disease 3% of men and 8% of women in the UK • Sideroblastic anaemia
Pathophysiology: Iron deficiency anaemia
Aetiology: Iron deficiency anaemia Age group Cause Infants • Malnutrition • Breast feeding Children • Malnutrition • Malabsorption • E.g. Coeliac disease Adults • Peptic ulcer disease • Menorrhagia • Malabsorption • E.g. Coeliac disease Elderly • Colon cancer
Question 2 A 20-year-old lady presents to the GP with lethargy. She is a medical student and complains of intense fatigue, struggling to stay awake during lectures. As soon as she gets home, she goes straight to bed. She reveals that she often has heavy periods. Observations: HR 80, BP 118/77, RR 18, SpO2 98%, Temp 37.0 Q3 Q5 Q4 Q1 Q2 You confirm a microcytic anaemia. Which of the following tests should be conducted next if you suspect iron deficiency? Serum iron Transferrin Ferritin Total iron binding capacity Urinary iron app.bitemedicine.com 14
Explanations Q5 Q3 Q4 Q1 Q2 You confirm a microcytic anaemia. Which of the following tests should be conducted next if you suspect iron deficiency? Serum iron Can be unreliable due to diurnal variation and can vary between labs Transferrin NICE advise measuring ferritin Ferritin NICE advises measuring this first-line. Low in iron deficiency Total iron binding capacity NICE advise measuring ferritin Urinary iron This is not measured app.bitemedicine.com 15
Aetiology: Iron deficiency anaemia Cause Reduced intake • Malnutrition • Breastfeeding • Malabsorption • Coeliac disease Increased requirement • Pregnancy Increased loss • Chronic bleeding • Colon cancer • Menorrhagia • Peptic ulcer disease
Clinical features: Iron deficiency anaemia Features Glossitis Angular stomatitis/chelitis Koilonychia (1) Pica (2)
A 20-year-old lady presents to the GP with lethargy. She is a medical student and Question 3 complains of intense fatigue, struggling to stay awake during lectures. As soon as she gets home, she goes straight to bed. She reveals that she often has heavy periods. Observations: HR 80, BP 118/77, RR 18, SpO2 98%, Temp 37.0 Q5 Q1 Q3 Q4 Q2 Which of the following is true for a patient with iron deficiency anaemia? Treat with blood transfusion Treat with intravenous iron Arrange urgent upper GI endoscopy if ≥50 Arrange urgent colonoscopy if ≥ 60 Arrange urgent colonoscopy if ≥65 app.bitemedicine.com 18
Q1 Q2 Q3 Q4 Q5 Explanations Which of the following is true for a patient with iron deficiency anaemia? Treat with blood transfusion Oral iron is first line Treat with intravenous iron Oral iron is first line. IV iron can be used if oral therapy not tolerated Arrange urgent upper GI endoscopy if ≥50 Not indicated unless suspecting an upper GI bleed in any age group Arrange urgent colonoscopy if ≥ 60 As per NICE guidelines Arrange urgent colonoscopy if ≥65 NICE suggest ≥ 60 app.bitemedicine.com 19
Investigations: Iron deficiency anaemia Bloods FBC: microcytic anaemia (MCV <80fL) • Blood film: hypochromic red cells, target cells • Iron studies • Ferritin: reduced • Serum iron: reduced • TIBC: increased • Transferrin saturation: decreased • Imaging Endoscopy • Suspecting upper GI bleed • ≥60 years old with iron deficiency anaemia • Special tests Coeliac serology • 20
Management: Iron deficiency anaemia Address the underlying cause Oral iron replacement Ferrous sulphate or ferrous fumarate • Monitor Hb 2-4 weeks after starting and then at 2-4 months • Treatment should continue for 3 months after anaemia corrected • Intravenous iron replacement Not responding or intolerant to oral therapy • Malabsorption • Renal failure • Blood transfusion Hb <70g/L or • Hb <80g/L and cardiac co-morbidity • 21
Case-based discussion: 2 History and examination A 1-year-old child is brought to the GP as his mother is concerned he is not gaining weight. He is dropping off the centiles on his growth chart. On examination he appears pale and has evidence of hepatosplenomegaly. His forehead looks prominent. Further investigations reveal a diagnosis of beta thalassaemia major. (3) 22
A 1-year-old child is brought to the GP as his mother is concerned he is not Question 1 gaining weight. He is dropping off the centiles on his growth chart. On examination he appears pale and has evidence of hepatosplenomegaly. His forehead looks prominent. Further investigations reveal a diagnosis of beta Thalassaemia major. Q1 Q2 Which of the following would you expect to see on haemoglobin electrophoresis in this patient? Raised HbH Raised HbA Raised HbA 2 Reduced HbF HbS app.bitemedicine.com 23
Q1 Q2 Question 1 Which of the following would you expect to see on haemoglobin electrophoresis? Raised HbH Associated with alpha thalassaemia Raised HbA Reduced in beta thalassaemia Raised HbA 2 Raised along with HbF Reduced HbF Should be raised HbS Associated with sickle cell disease app.bitemedicine.com 24
Introduction: Thalassaemia Microcytic anaemia Definition: autosomal recessive haemoglobinopathy Impaired globin chain synthesis • Iron deficiency Thalassaemia Epidemiology: Anaemia of chronic disease Prevalent in areas of malaria • Alpha thalassaemia: Asian and African Sideroblastic anaemia • Beta thalassaemia: Asian, Mediterranean and Middle Eastern •
Pathophysiology: Thalassaemia Normal Hb Structure Proportion in adults Alpha thalassaemia Beta thalassaemia HbA α 2 β 2 90% Reduced Reduced HbA 2 α 2 δ 2 <2% Reduced Increased HbF <2-5% α 2 γ 2 Reduced Increased
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