Aims and objectives Recap of haematology: anaemia, malignancies and - PowerPoint PPT Presentation

Aims and objectives Recap of haematology: anaemia, malignancies and clotting • Start with easy questions and gets progressively harder • 35 seconds to answer • Question 1: answer quickly • Total number of questions: 12 • Duration: 60 mins • Slides and recordings: app.bitemedicine.com • 2

Question 1 5

Explanations A 25-year-old lady presents with lethargy. She complains of a craving for ice. Her Hb is 90g/L. What is your first-line investigation? Serum iron In anaphylaxis, antihistamine should be given after adrenaline and fluids Ferritin NICE advises measuring this first-line. Low in iron deficiency Transferrin NICE advise measuring ferritin Total body iron This is not measured Urinary iron This is not measured app.bitemedicine.com 6

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)

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 • 9

Question 2 10

Explanations A 4-year old girl presents with lethargy. Her Hb is 100 g/L and MCV 85fL. What is the likely cause? Thalassemia Microcytic anaemia (MCV < 80) G6PD deficiency X-linked recessive → seen in males Hereditary spherocytosis A hereditary cause of normocytic anaemia. Usually autosomal dominant Autoimmune haemolytic anaemia Rare in this age group. Associated with underlying conditions e.g. SLE or CLL, or with drugs Iron deficiency anaemia Microcytic anaemia (MCV < 80) app.bitemedicine.com 11

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 12

Question 3 13

Explanations Which of the following is the most appropriate treatment for this 4-year-old girl with hereditary spherocytosis? Splenectomy Should be delayed Delay splenectomy till 6 years of age Delayed to reduce risk of post-splenectomy sepsis Delay splenectomy till 10 years of age Delayed till age 6 Stem cell transplant Not carried out Regular venesection (phlebotomy) Will exacerbate anaemia. This is a treatment for hereditary haemachromatosis app.bitemedicine.com 14

Hereditary spherocytosis Definition: inherited defect in RBC membrane proteins leading to a haemolytic anaemia Usually autosomal dominant • Epidemiology: Northern European and North American populations • 1 in 2000 people •

Pathophysiology: Hereditary spherocytosis RBC membrane proteins: Spectrin • Ankyrin • Band 3 • Protein 4.2 •

Investigations: Hereditary spherocytosis (2) 17

Management: Hereditary spherocytosis Neonatal jaundice Phototherapy or exchange transfusion • Blood transfusion Hb <70g/L or • Hb <80g/L and cardiac co-morbidity • Folic acid Daily until splenectomy • Splenectomy Spleen removal reduces haemolysis • Delayed until patients are >6 years of age to reduce the risk of post-splenectomy sepsis • 18

Question 4 19

Explanations A 9-month-old child is failing to thrive, and investigations reveal a diagnosis of beta thalassemia major. Which of the following would you expect? Raised HbH Associated with alpha thalassaemia Raised HbA Reduced in beta thalassaemia Raised HbA 2 Raised along with HbF Raised HbS Associated with sickle cell anaemia Reduced HbF Should be raised app.bitemedicine.com 20

Introduction: Thalassaemia Definition: autosomal recessive haemoglobinopathy Impaired globin chain synthesis • Epidemiology: Prevalent in areas of malaria • Alpha thalassaemia: Asian and African • 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

Question 5 23

Explanations A 40-year-old type 1 diabetic has Hb 95 g/L and MCV 110 fL. Which of the following is the most sensitive investigation for the likely diagnosis? Anti-GAD T1DM ANA Seen in connective tissue diseases e.g. SLE Anti-parietal cell Pernicious anaemia: most sensitive Anti-intrinsic factor Pernicious anaemia: most specific Anti-tTG Coeliac disease app.bitemedicine.com 24

Pathophysiology: Pernicious anaemia Definition: autoimmune process affecting vitamin B12 absorption Epidemiology: Most common cause of vitamin B12 deficiency • Risk factors: Females > males • Autoimmunity: Addison’s disease, vitiligo, T1DM •

Question 6 26

Explanations A 50-year-old presents with lethargy and weight loss. O/E there is hepatosplenomegaly and gum hyperplasia. What is the likely translocation involved? t(15;17) APML t(9;22) CML t(8;14) Burkitt lymphoma t(11;14) Mantle cell lymphoma None of the above Gum hyperplasia suggests a diagnosis of AML (subtype monocytic) app.bitemedicine.com 27

Introduction: Malignancy 28

Pathophysiology: Acute myeloid leukaemia 9 subtypes of AML (FAB classification) Acute promyelocytic leukaemia (M3) t(15;17): fusion of retinoic acid receptor with • promyelocytic protein which blocks maturation Younger patients ~ 45 years old • Associated with disseminated intravascular • coagulation Good prognosis • Acute monocytic leukaemia (M5) Monoblast accumulation • Gum infiltration • (1)

Question 7 30

Explanations A 70-year-old presents with lethargy. O/E there is massive splenomegaly. Bone marrow biopsy shows fibrosis. What is the neoplastic cell? Erythrocyte Neoplastic cell in PCV Lymphocyte Neoplastic cell in certain leukaemias and all lymphomas Platelet Neoplastic cell in essential thrombocytosis Megakaryocyte Proliferation of the megakaryocyte leads to marrow fibrosis Granulocyte Neoplastic cell in AML/CML app.bitemedicine.com 31

Introduction: Myelofibrosis Definition: myeloproliferative condition. Neoplastic proliferation of mature myeloid cells, particularly megakaryocytes Leading to marrow fibrosis • Risk factors Age: >65 years • Radiation •

Pathophysiology: Myelofibrosis (1)

Question 8 34

Explanations Which of the following is suggestive of myeloma? Rouleaux formation Stacked RBCs seen in myeloma Smudge cell CLL Auer rods AML Spherocytes Hereditary spherocytosis and autoimmune haemolytic anaemia Lymphoblasts ALL app.bitemedicine.com 35

Pathophysiology: Myeloma (3) (4)

Investigations: Myeloma (5)

Question 9 38

Explanations A 40-year old lady with a background of Hashimoto's thyroiditis presents with a nodule in the neck. What is the likely diagnosis? Follicular lymphoma Not associated with Hashimoto’s thyroiditis Burkitt lymphoma Not associated with Hashimoto’s thyroiditis Marginal zone lymphoma Associated with chronic inflammatory states Mantle zone lymphoma Not associated with Hashimoto’s thyroiditis Hodgkin lymphoma Not associated with Hashimoto’s thyroiditis app.bitemedicine.com 39

Marginal Zone Lymphoma Marginal zone Mantle zone Germinal centre

Marginal Zone Lymphoma Definition: proliferation of small B cells that expand marginal zone Pathophysiology: Can occur in lymph nodes or spleen • Extranodal sites: • Gastric MALToma (mucosa associated lymphatic tissue): • H.pylori infection Thyroid gland: Hashimoto’s thyroiditis • Salivary gland: Sjögren's syndrome • Clinical: Adults • Underlying condition •

Question 10 42

Explanations A 10-year-old presents with petichae on his limbs. He had a viral URTI 2 weeks ago. Which of the following antigens is implicated in this disease? GpIIb/IIIa Idiopathic thrombocytopaenic purpura → IgG against GpIIb/IIIa Platelet factor 4 Associated with HIT Factor VIII Deficiency in Haemophilia A GpIb Deficiency in Bernard-Soulier disease Von Willebrand factor Deficency/impaired function in Von Willebrand disease app.bitemedicine.com 43