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kml20@ic.ac.uk Anaemia MedEd Y3 Written Exam Lectures 2023 Kate Larard, slides edited from Adele SchiffSESSION CONTENT From Sofia: 1. Anaemia 2. Haemoglobinopathies 3. Myeloproliferative disorders (polycythemia) 4. Vitamin B12 and/or folate deficiencyAnaemia Haemoglobin level two standard deviations below the normal for age and sex. Men - 130-180 g/L/L Reduced haemoglobin à impaired oxygen delivery à symptoms Anaemia Mean Corp(MCV)ar Volume Microcytic Anaemia Macrocytic Anaemia Normocytic Anaemia Anaemia Overview Anaemia Impaired Haemoglobin Synthesis Microcytic Anaemia Normocytic Anaemia Macrocytic Anaemia 1. Iron Deficiency Megaloblastic Anaemia 1. Myelofibrosis 1. B12 Deficiency 2. Anaemia of Chronic 2. Acute Blood Loss Disease 3. Aplastic Anaemia 2. Folate Deficiency 3. Thalassemia 4. Haemolytic Non-Megaloblastic 4. Sideroblastic Anaemias 1. Myelodysplasia Anaemia 2. Alcohol 3. Hypothyroidism Acquired 4. Pregnancy Congenital Non Auto-immune 1. G6PD 1. Drugs 2. Hereditary 2. Infection: Malaria Auto-immune Spherocytosis 3. HUS/TTPIron Deficiency Anaemia Causes Investigations: Symptoms + Signs: Reduced Uptake 1. FBC: microcytic anaemia 1. Fatigue 1. Inflammatory Bowel Disease 2. Blood Film 2. SOB (IBD) 3. Iron Studies: 3. Pallor 2. Malnutrition Ferritin – LOW 4. Palpitations 3. Coeliac Disease Serum Iron – LOW 5. Atrophic glossitis Ferroportin - HIGH 6. Angular stomatitis Increased loss: Total iron binding capacity (TIBC) / Transferrin - HIGH 7. Koilonchyia 1. Gastro-intestinal (GI) Malignancy 2. IBD 3. Menstruation Colon Cancer • Change in 4. Peptic Ulcer Disease bowel habit Management: • PR bleeding Increased Demand: 1. Pregnancy 1. Find out the underlying cause • IDA 2. Breast feeding 2. Oral ferrous sulfate – and continue 3 months after • (+FLAWS) iron levels replenish 3. Iron-rich dietIron Deficiency Anaemia Blood Film Features: • Hypochromic + Microcytic • Anisopoikilocytosis • Pencil cells • Target cells Anaemia of Chronic Disease Chronic disease state -Infection -Malignancy -Diabetes -Autoimmune disorders Symptoms and Signs • Anaemia with a chronic disease • Usually starts normocytic and leads to microcyticChronic Disease Vs Iron Deficiency Iron Deficiency Anaemia Anaemia of Chronic Disease (IDA) (ACD) Haemoglobin (Hb) Low Low Serum Iron Low <8 Low <15 Ferroportin High Low Ferritin Low High / normal Transferrin High Low Thalassemia • Defect in globin synthesis • SBA Epidemiology: Mediterranean, (Cyprus) South Asian, and Middle Eastern origin Blood film: Hypochromic, microcytic red blood cells Alpha Thalassemia • 2 alpha-globulin genes on each chromosome 16, giving a total of 4 genes 1 or 2 alpha globulin alleles affected: Usually asymptomatic 4 alpha globulin alleles affected: 3 alpha globulin alleles affected: HbH Disease Death in utero • Features of anaemia, Haemolysis, Splenomegaly, (hydrops fetalis, Bart's hydrops) • Diagnosis: Hb Electrophoresis (HbH instead of HbA1) Management: life-long blood transfusions, chelating therapy Beta Thalassemia • 1 beta-globin gene on each chromosome 11, giving a total of 2 genes 1 beta globin gene affected: Beta Trait • Typically asymptomatic 2 beta globin gene affected: Beta Major • Diagnosis: Hb electrophoresis – HbA1 absent, HbA2 + HbF raised • Management: life-long blood transfusions, chelating therapy Sideroblastic Anaemia Defect in Haem synthesis • ALA synthase deficiency/impairment leading to excess iron accumulation Investigations: Blood film: Ringed Sideroblast Causes: Congenital: ALA synthase deficiency Acquired: 1. Alcohol 2. Vitamin B6 deficiency 3. Lead poisoning Management Congenital – Pyridoxine (Vit B6) Acquired - Treat cause Buzzword Quiz What does pencil cells suggest on a blood film? Iron Deficiency Anaemia What is a differentiator between Iron Deficiency Anaemia Ferroportin, Ferritin, Transferrin and Chronic Disease in terms of iron studies? What disease occurs when there are 3 mutations in the HbH alpha globin alleles? What does ringed sideroblasts suggest on a blood film? Sideroblastic anaemia Which ethnicities have higher rates of thalassaemia? Mediterranean, South Asian, Middle Eastern What are the types of beta thalassaemia? Difference? Minor (1 mutation), Major (2 mutation, blood transfusions) SBA 1 (question) A 24 year old woman from Greece comes into the GP complaining of excessive tiredness. She explains that recently when she is exercising she feels short of breath and has been feeling her heart beat really fast. The GP decides to run blood tests, which demonstrate a low serum ferritin and high total iron binding capacity. What is the most likely diagnosis? a) Anaemia of Chronic Disease b) Beta Thalassemia Major c) HbH Disease d) Iron Deficiency Anaemia e) Sickle Cell Crisis SBA 1 (answer) A 24 year old woman from Greece comes into the GP complaining of excessive tiredness. She explains that recently when she is exercising she feels short of breath and has been feeling her heart beat really fast. The GP decides to run blood tests, which demonstrate a low serum ferritin and high transferrin. Iron Deficiency Anaemia of Chronic Anaemia (IDA) Disease (ACD) What is the most likely diagnosis? Haemoglobin (Hb) Low Low a) Anaemia of Chronic Disease b) Beta Thalassemia Major Serum Iron Low <8 Low <15 Ferroportin High Low c) HbH Disease d) Iron Deficiency Anaemia Ferritin Low High / normal e) Sickle Cell Crisis Transferrin High LowAnaemia Overview Anaemia Microcytic Anaemia Normocytic Anaemia Macrocytic Anaemia 1. Iron Deficiency Megaloblastic Anaemia 1. Myelofibrosis 1. B12 Deficiency 2. Thalassemia 2. Acute Blood Loss 3. Anaemia of 3. Aplastic Anaemia 2. Folate Deficiency Chronic Disease 4. Haemolytic Non-Megaloblastic 4. Sideroblastic Anaemias 1. Myelodysplasia anaemia 2. Alcohol 3. Hypothyroidism Acquired 4. Pregnancy Congenital Non Auto-immune 1. G6PD 1. Drugs 2. Hereditary 2. Infection: Malaria Auto-immune Spherocytosis 3. HUS/TTP Myeloproliferative/Myelodysplasia Increase in Does not make one/mixture of cell healthy red blood lineage cells – Macrocytic anaemia Myelofibrosis – microcytic anaemia MYELOFIBROSIS • Myeloproliferative disorder • Growth of abnormal cells in bone marrow à neoplasm Management • Usually an elderly person • Supportive measures Signs and Symptoms • Stem Cell transplant • Normocytic anaemia • Immunomodulatory drugs such as • Massive splenomegaly – differentiate from Thalidomide myelodysplasia Investigations • FBC - Low Hb • Blood film - Tear drop rbc • Bone marrow biopsy – dry tap • Genetics - JAK2 mutation SBA 2 (question) A 68-year-old female comes in complaining of extreme fatigue. On further examination, splenomegaly and hepatomegaly is noted. The doctor orders a range of blood tests, including a bone marrow aspirate with a dry tap. What is the most likely finding on a blood film? a) Dry-tap b) Howell Jolly Bodies c) Pencil cells d) Target cells e) Tear-drop polikiloyctes SBA 2 (answer) A 68-year-old female comes in complaining of extreme fatigue. On further examination, splenomegaly and hepatomegaly is noted. Further questioning reveals she has had recent night sweats and weight loss. The doctor orders a range of blood tests, including a bone marrow aspirate with a dry tap. What is the most likely finding on a blood film? a) Dry-tap b) Howell Jolly Bodies c) Pencil cells d) Target cells e) Tear-drop polikiloyctesAnaemia Overview Anaemia Microcytic Anaemia Normocytic Anaemia Macrocytic Anaemia Megaloblastic 1. Iron Deficiency 1. Myelofibrosis 1. B12 Deficiency Anaemia 2. Acute Blood Loss 2. Thalassemia 3. Aplastic Anaemia 2. Folate Deficiency 3. Anaemia of 4. Haemolytic Non-Megaloblastic Chronic Disease Anaemias 1. Myelodysplasia 2. Alcohol 3. Hypothyroidism Acquired 4. Pregnancy Congenital Non Auto-immune 1. G6PD deficiency 1. Drugs 2. Hereditary 2. Infection: Malaria Auto-immune Spherocytosis 3. HUS/TTPAnaemia Overview Anaemia Microcytic Anaemia Normocytic Anaemia Macrocytic Anaemia 1. Iron Deficiency Megaloblastic Anaemia 1. Myelofibrosis 1. B12 Deficiency 2. Thalassemia 2. Acute Blood Loss 3. Anaemia of 3. Aplastic Anaemia 2. Folate Deficiency Chronic Disease 4. Haemolytic Non-Megaloblastic 4. Sideroblastic Anaemias 1. Myelodysplasia anaemia 2. Alcohol 3. Hypothyroidism Acquired 4. Pregnancy Congenital Non Auto-immune 1. G6PD deficiency 1. Drugs 2. Hereditary 2. Infection: Malaria Auto-immune Spherocytosis 3. HUS/TTP G6PD Deficiency • X linked recessive – MALES Investigations: • Mediterranean/Africa • Blood film - Heinz bodies, bite and blister cells Triggers • Diagnosis test: G6PD enzyme assay (3 • Illness/ infection months after acute episode) • FAVA beans • Medications e.g. anti-malarial, ciprofloxacin Symptoms • Episodic anaemia • Increased rbc breakdown – splenomegaly, gallstones, dark urine Management • Avoid triggers • (some rely on transfusions) Hereditary Spherocytosis • Autosomal DOMINANT – defect in vertical Management linkages • Conservative: Folic acid • Northern European supplement • Severe: splenectomy Symptoms (before 5 is curative) 1. Anaemia from birth 2. Increased rbc breakdown – jaundice, gallstones, dark urine 3. Splenomegaly Complications Aplastic crisis (usually with Investigations paravirus before) 1. Blood film: Spherocytes (round + lack central pallor) 2. Reduced EMA binding (in past was an Need blood transfusion osmotic fragility test)Anaemia Overview Anaemia Microcytic Anaemia Normocytic Anaemia Macrocytic Anaemia 1. Iron Deficiency Megaloblastic Anaemia 1. Myelofibrosis 1. B12 Deficiency 2. Thalassemia 2. Acute Blood Loss 3. Anaemia of 3. Aplastic Anaemia 2. Folate Deficiency Chronic Disease 4. Haemolytic Non-Megaloblastic 4. Sideroblastic Anaemias 1. Myelodysplasia anaemia 2. Alcohol 3. Hypothyroidism Acquired 4. Pregnancy Congenital Non Auto-immune 1. G6PD deficiency 1. Drugs 2. Hereditary 2. Infection: Malaria Auto-immune Spherocytosis 3. HUS/TTPAutoimmune Haemolytic Anaemia Symptoms: Investigations: • Anaemia • FBC – low Hb POSITIVE DIRECT ANTIGLOBULIN TEST • Increased rbc breakdown – • HIGH LDH + HIGH unconjugated bilirubin jaundice, gallstones, dark urine • Blood film: Reticulocytes (COOMBS +ve) WARM AIHA COLD AIHA • Most common • IgM • IgG Causes: Causes 1. Infection e.g. EBV, mycoplasma 1. Idiopathic 2. Autoimmune disease e.g. SLE 3. Drugs e.g. methyldopa Management • Treatment of any underlying disorder • Steroids (+/- rituximab) are generally used first-line Haemolytic Uraemic Syndrome TRIAD Investigations 1. Acute kidney injury FBC: 2. Microangiopathic haemolytic anaemia • Low Hb 3. Thrombocytopenia • Thrombocytopenia Anaemia caused by Blood film: rbc being ‘cut up’ in Schistocytes NEGATIVE DIRECT U+Es – AKI ANTIGLOBULIN TEST blood vessels (COOMBS -ve) Classic presentation Young child, bloody diarrhea, rash, abdo pain Causes E.coli (STEC) 0157:H7Thrombotic Thrombocytopenia Purpura (TTP) Management Plasma exchange (contains ADAMTS13) Pentad: 1. Acute kidney injury 2. Microangiopathic haemolytic anaemia 3. Thrombocytopenia 4. Temperature 5. Swinging CNS signs Defect in ADAM-TS-13 Enzyme Buzzword Quiz What is the inheritance pattern of G6PD deficiency? X- linked What does a DAT +ve test indicate in regards to AIHA? Autoimmune cause What does Heinz Bodies on a blood film suggest? G6PD deficiency What is the triad of issues with HUS? AKI, MAHA, Thrombocytopenia What is the pentad of issues with TTP? AKI, MAHA, Thrombocytopenia + fever, neuro issues SBA 3 (question) A young boy comes into the GP clinic complaining of excessive tiredness following a bad flu a few weeks ago. On examination splenomegaly is noted. Blood tests are run and a blood film is done revealing Heinz bodies, bite and blister cells. What is the most likely diagnosis ? a) Hereditary Spherocytosis b) G6PD deficiency c) Warm Auto-immune haemolytic anaemia d) Cold Auto-immune haemolytic anaemia e) HUS SBA 3 (answer) A young boy comes into the GP clinic complaining of excessive tiredness following a bad flu a few weeks ago. On examination splenomegaly is noted. Blood tests are run and a blood film is done revealing Heinz bodies, bite and blister cells. What is the most likely diagnosis ? a) Hereditary Spherocytosis b) G6PD deficiency c) WARM AIHA d) ITP e) HUSAnaemia Overview Anaemia Microcytic Anaemia Normocytic Anaemia Macrocytic Anaemia Megaloblastic 1. Iron Deficiency 1. Myelofibrosis 1. B12 Deficiency Anaemia 2. Acute Blood Loss 2. Thalassemia 2. Folate Deficiency 3. Anaemia of 3. Aplastic Anaemia Chronic Disease 4. Haemolytic Non-Megaloblastic 4. Sideroblastic Anaemias 1. Myelodysplasia anaemia 2. Alcohol 3. Hypothyroidism Acquired 4. Pregnancy Congenital Non Auto-immune 1. G6PD 1. Drugs 2. Hereditary 2. Infection: Malaria Auto-immune Spherocytosis 3. HUS/TTP Deficiency – B12, Folate B12 Symptoms Anaemia + Neuro + Skin Causes • Hyporeflexia Poor absorption: • Mood disturbances • Pernicious anaemia • Sore tongue and mouth • Post-gastroectomy Less neuro signs with folate deficiency • Chron’s Reduced Intake: 1. Vegan/poor-diet Investigations • FBC: HIGH MCV, LOW Hb Folate • Blood film: Causes HYPERSEGMENTED NEUTROPHILS Poor absorption: • Alcohol • Coeliac disease • Anti-folate drug Increased use: • Pregnancy Management • Replace - IM hydroxocobalamin, Oral Folic acid • Treat vitamin B12 deficiency before folic acid to avoid precipitating subacute combined degeneration of the cord Pernicious Anaemia Autoimmune condition • Auto-antibodies targeted against intrinsic factor (IF) or Gastric Parietal Cells Risk Factors • European descent • Other autoimmune disease e.g. Addison’s • Blood group type A Risks • 3x Increased risk of gastric cancer • B12 Deficiency Investigations - Antibody test: • Intrinsic factor antibodies • Gastric parietal cell antibodies SBA 4 (question) A young vegan female comes into clinic, she is really tired. Blood tests reveal a high mean cell volume and low haemoglobin and hypersegmented neutrophils are noted. A diagnosis of vitamin B12 deficiency and folate deficiency is made. A discussion is had and she refuses to include animal products in her diet due to her personal beliefs. a)at Dietary adviceine treatment? b) Folic acid supplements c) 1 mg of IM hydroxocobalamin d) Do nothing and redo bloods in 3 weeks e) Pyridoxine SBA 4 (answer) A young vegan female comes into clinic, she is tired. Blood tests reveal a high mean cell volume and low haemoglobin and hypersegmented neutrophils are noted. A discussion is had and she refuses to include animal products in her diet due to her personal beliefs. What is the first-line treatment? a) Dietary advice b) Folic acid supplements c) 1 mg of IM hydroxocobalamin d) Do nothing and redo bloods in 3 weeks e) Pyridoxine Myelodysplastic Syndrome • Pre-leukaemia (as can progress to AML) No splenomegaly Risk Factors: • Elderly • Caucasian • Male • Previous radio/chemotherapy • Genetic – Fanconi anaemia, Downs syndrome Investigations • Low platelets • Low hb • Low neutrophils • High MCV Management: • Supportive management • G-CSF • Chemotherapy • Stem Cell Transplant Buzzword Quiz What are the two categories in macrocytic anaemia? Megaloblastic and non-megaloblastic What do you need to check before replacing folate B12 – subacute combined degeneration of the cord deficiency? What does hypersegmented neutrophils on a blood film Megaloblastic anaemia – B12/folate deficiciency suggest? What are the antibodies tested for in pernicious Intrinsic factor antibodies, Gastric parietal cell antibodies anaemia? Myeloproliferative/Myelodysplasia Increase in Does not make one/mixture of cell healthy red blood lineage cells – Macrocytic anaemia Myelofibrosis – microcytic anaemiaMyeloproliferative Syndrome Disease of the elderly Rarely can transform into AML Chronic Myeloid Leukaemia Polycythaemia Vera Essential ThrombocytosisEssential Thrombocytosis • Megakaryocyte proliferation results in overproduction of platelets Management • Low dose aspirin • Hydroxyurea • Good prognosis Symptoms • 50% asymptomatic • Thrombosis • Intracranial / gastrointestinal bleeding Signs • Splenomegaly • Livedo reticularis Investigations • Increased platelet count (>450-600 x 10^9/L) • JAK2 v617F mutation in 50-60% of essential thrombocytosis Polycythemia Vera • High number of red blood cells in blood Investigations • High Haemtocrit • Low EPO • 95% JAK2 mutation Management • Venesection • Chemotherapy 1.6x increased risk of thrombosis Symptoms and signs: • Pruritis after hot bath • Splenomegaly • hyperviscosity – thrombosis • hypertensionChronic Myeloid Leukaemia Overproduction of white blood cells Symptoms • Increased infections • Fatigue • Weight loss • Bone pain Signs • Splenomegaly Management: Investigations TKI inhibitor – imatinib • Increased wbc Stem cell transplant • Blood film - myelocytes • FISH – t(9;22) SBA 4 (question) A 55-year-old male presents to the clinic with complaints of fatigue, weight loss, and excessive sweating over the past few months. On examination, he has splenomegaly. His FBC shows a platelet count of 450 x 10^9/L. A bone marrow biopsy reveals hypercellularity with an increased number of megakaryocytes. Given the likely diagnosis, what would you like to begin immediately? a) Imatinib b) Aspirin c) Chemotherapy d) Hydroxyurea e) Venesection SBA 3 (answer) A 55-year-old male presents to the clinic with complaints of fatigue, weight loss, and excessive sweating over the past few months. On examination, he has splenomegaly. His FBC shows a platelet count of 450 x 10^9/L. A bone marrow biopsy reveals hypercellularity with an increased number of megakaryocytes. Given the likely diagnosis, what would you like to begin immediately? a) Imatinib b) Aspirin c) Chemotherapy Arachidonic acid d) Hydroxyurea e) Venesection Platelet aggregationAnaemia Overview Anaemia Microcytic Anaemia Normocytic Anaemia Macrocytic Anaemia Megaloblastic 1. Iron Deficiency 1. Myelofibrosis 1. B12 Deficiency Anaemia 2. Acute Blood Loss 2. Thalassemia 2. Folate Deficiency 3. Anaemia of 3. Aplastic Anaemia Chronic Disease 4. Haemolytic Non-Megaloblastic 4. Sideroblastic Anaemias 1. Myelodysplasia anaemia 2. Alcohol 3. Hypothyroidism Acquired 4. Pregnancy Congenital Non Auto-immune 1. G6PD 1. Drugs 2. Hereditary 2. Infection: Malaria Auto-immune Spherocytosis 3. HUS/TTP Anaemia Overview Microcytic Anaemia Macrocytic Anaemia Sideroblastic Anaemia Size Megaloblastic Isn’t 1. B12 Deficiency Iron Deficiency Anaemia 2. Folate Deficiency T halassemia T hat C rucial Anaemia of C hronic Disease Non-Megaloblastic 1. Myelodysplasia 2. Alcohol Normocytic Anaemia 3. Hypothyroidism 4. Pregnancy Normally Myelofibrosis My Acute Blood Loss Animal Aplastic Anaemia Appears Haemolytic Anaemias HealthyTHANK YOU FOR COMING! PLEASE FILL IN THE FEEDBACK FORM!