Aims and objectives Why is haematology so difficult? • Classification of malignancies • Haematology is a specialist area • Only learn what you need to know for exams • Duration: 70 mins • Slides and recordings: app.bitemedicine.com • 2
Case-based discussion: 1 History and examination A 55-year-old male presents with a 3-week history of tiredness and weight loss. On examination, you note bruising on his legs and hepatosplenomegaly. Observations (1) HR 80, BP 118/77, RR 18, SpO2 98%, Temp 37.0 3
Question 1 A 45-year-old male presents with a 3-week history of tiredness and weight loss. On examination, you note bruising on his legs and hepatosplenomegaly. Observations: HR 80, BP 118/77, RR 18, SpO2 98%, Temp 37.0 Q1 Q2 Which of the following is the most likely diagnosis? Acute myeloid leukaemia Chronic myeloid leukaemia Acute lymphoblastic leukaemia Chronic lymphocytic leukaemia Hodgkin lymphoma app.bitemedicine.com 4
Case-based discussion: 1 History and examination A 45-year-old male presents with a 3-week history of tiredness and weight loss. On examination, you note bruising on his legs and hepatosplenomegaly. Observations (1) HR 80, BP 118/77, RR 18, SpO2 98%, Temp 37.0 5
Introduction: Haematopoiesis (2) 6
(3) 7
Introduction: Malignancy 8
Clinical features: General principles Symptoms/Signs Bone marrow failure Anaemia • Fatigue • Pallor Thrombocytopaenia • Bleeding: bruising and epistaxis Dysfunctional white cells • Recurrent infections Constitutional symptoms Weight loss Fatigue Fever Loss of appetite Infiltration Hepatosplenomegaly Lymphadenopathy Gum hyperplasia (AML) 9
Investigations: General principles Bedside Full set of observations • Bloods FBC • Blood film • Clotting screen • Imaging CT imaging • Special tests Bone marrow aspirate and biopsy • Lymph node biopsy • Immunophenotype • Genetic testing • 10
Introduction: Acute myeloid leukaemia Myeloid Definition: proliferation of immature myeloid cells Immature = acute leukaemia • AML Mature = chronic leukaemia • CML Epidemiology: Myelofibrosis Most common acute leukaemia in adults • Polycythaemia vera 3000 cases per year in the UK (cancer research UK) • Essential thrombocytosis Risk factors Age: average age of diagnosis is 68 years old • Myelodysplasia: precursor lesion and evolves to AML in 30% of • cases Chemotherapy • Radiotherapy •
Question 2 A 45-year-old male presents with a 3-week history of tiredness and weight loss. On examination, you note bruising on his legs and hepatosplenomegaly. Observations: HR 80, BP 118/77, RR 18, SpO2 98%, Temp 37.0 Q1 Q2 Which of the following translocations is associated with AML? t(9;22) t(8;14) t(12;21) t(15;17) t(14;18) app.bitemedicine.com 12
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 • (4)
Pathophysiology: Acute myeloid leukaemia Myelodysplasia (NOT MYELOFIBROSIS!) Neoplastic proliferation of immature myeloid cells • with evidence of dysplasia Pre-cursor lesion to AML • 30% of cases progress to AML • Blast cells on marrow <20% • (4)
Investigations & Management: Acute myeloid leukaemia Investigations FBC: leukocytosis, thrombocytopaenia, anaemia • Blast cells crowd out bone marrow causing low PLTs and Hb • Blood film: immature myeloid cells with auer rods • Clotting screen: deranged in disseminated intravascular coagulation • Bone marrow biopsy: ≥ 20% myeloblasts is diagnostic • Cytogenetic studies: t(15;17) • Management Induction • APML: all-trans retinoic acid • Consolidation •
Investigations & Management: Acute myeloid leukaemia Auer rods: aggregates of myeloperoxidase Seen in immature myeloid • cells (5)
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Introduction: Chronic myeloid leukaemia Myeloid Definition: myeloproliferative condition. Neoplastic proliferation of mature myeloid cells (granulocytes and their precursors) AML Immature = acute leukaemia • Mature = chronic leukaemia • CML Myelofibrosis Risk factors Age: 65-75 years of age • Polycythaemia vera Radiation • Essential thrombocytosis
Q1 Question 3 Once CML is confirmed, which of the following is first-line management? All-trans retinoic acid Imatinib Stem cell transplant IFN alpha Hydroxyurea app.bitemedicine.com 19
Pathophysiology: Chronic myeloid leukaemia Tyrosine kinase activity Constitutive activity • (4) (6)
Investigations & Management: Chronic myeloid leukaemia Investigations FBC: leukocytosis, thrombocytosis or thrombocytopaenia, anaemia • Raised granulocyte count • Blood film: increased number of mature granulocytes (<10% blast cells) • Clotting screen: deranged in disseminated intravascular coagulation • Bone marrow biopsy: increased number of mature granulocytes • Myeloblasts not prevalent • Cytogenetic studies: Philadelphia chromosome t(9;22) • Leukaemia Prevalence of Philadelphia chromosome Management CML • 95% Tyrosine kinase inhibitor • Inhibits BCR-ABL fusion product AML • 2% • ALL • 5% children • 20% adults
Investigations & Management: Chronic myeloid leukaemia (7)
Complications: Chronic myeloid leukaemia Chronic phase Accelerated phase Blast transformation Summary Indolent and lasts many Progression of disease Transformation to acute years leukaemia with poor prognosis rd AML • 2/3 rd ALL • 1/3 Cell counts in blood <10% blast cells <20% blast cells ≥20% blast cells
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Introduction: Myelofibrosis Myeloid Definition: myeloproliferative condition. Neoplastic proliferation of mature myeloid cells, particularly megakaryocytes AML Leading to marrow fibrosis • CML Myelofibrosis Risk factors Age: >65 years • Polycythaemia vera Radiation • Essential thrombocytosis
Pathophysiology: Myelofibrosis (4)
Q1 Question 4 Which of the following is associated with myelofibrosis? Hypercellular bone marrow Lymphoblasts Smudge cell Teardrop red cell ‘Wet tap’ app.bitemedicine.com 27
Investigations & Management: Myelofibrosis Investigations FBC: anaemia, other cell counts may be low or variable • Blood film: leucoerythroblastic smear • Tear drop RBCs, nucleated RBCs, immature granulocytes • Bone marrow aspirate: ‘dry - tap’ • Bone marrow biopsy: marrow fibrosis • Genetics: JAK2 V617F mutation in 50-60% of patients • Management Chemotherapy •
Investigations & Management: Myelofibrosis (8)
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Introduction: Polycythaemia vera Myeloid Definition: myeloproliferative disorder. Neoplastic proliferation of mature myeloid cells, particularly RBCs AML Can also have thrombocytosis and granulocytosis • CML Risk factors Myelofibrosis Age: peak incidence 50-70 years of age • Male • Polycythaemia vera Essential thrombocytosis
Pathophysiology: Polycythaemia vera JAK2 V617F mutation (4)
Clinical features Clinical features related to hyperviscosity PCV Headache Blurry vision Flushed appearance Palmar erythema Itching after a bath (release of histamine) Erythromelalgia • Burning pain of extremities Increased risk of thrombosis 33
Q1 Question 5 In a patient with polycythaemia vera, which of the following should be started? Aspirin Warfarin Hydroxycarbamide (hydroxyurea) Imatinib Phenoxymethylpenicillin app.bitemedicine.com 34
Investigations & Management: Polycythaemia vera Investigations FBC: raised Hb and haematocrit • Granulocytes and PLTs may also be raised • EPO: low in polycythaemia vera • Raised in secondary polycythaemia e.g. hypoxia • Genetics: JAK2 V617F mutation in 95% of patients • Management Phlebotomy: aim for haematocrit <45% • Aspirin • Hydroxyurea: in patients at high risk of thrombosis e.g. >60 years of age •
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Introduction: Essential thrombocytosis Myeloid • Definition: myeloproliferative disorder. Neoplastic proliferation of mature myeloid cells, particularly megakaryocytes AML Increased risk of bleeding and/or thrombosis • CML Myelofibrosis Risk factors Age: >50-70 years of age • Polycythaemia vera Essential thrombocytosis
Pathophysiology: Essential thrombocytosis JAK2 V617F mutation (4)
Investigations & Management: Essential thrombocytosis Investigations FBC: thrombocytosis (PLTs > 600,000) • Bone marrow biopsy: increased megakaryocytes • Genetics: JAK2 mutation in 50-60% of patients • Management Antiplatelet e.g. aspirin • Hydroxycarbamide •
Recap 40
Top-decile question 41
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