Aims and objectives Why is haematology so difficult? - - PowerPoint PPT Presentation

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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

History and examination

A 55-year-old male presents with a 3-week history

• f 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

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Case-based discussion: 1

(1)

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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 Which of the following is the most likely diagnosis?

Question 1

Acute myeloid leukaemia Chronic myeloid leukaemia Acute lymphoblastic leukaemia Chronic lymphocytic leukaemia Hodgkin lymphoma app.bitemedicine.com

Q1 Q2

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

HR 80, BP 118/77, RR 18, SpO2 98%, Temp 37.0

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Case-based discussion: 1

(1)

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Introduction: Haematopoiesis

(2)

7 (3)

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Introduction: Malignancy

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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)

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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

Introduction: Acute myeloid leukaemia

Definition: proliferation of immature myeloid cells

• Immature = acute leukaemia
• Mature = chronic leukaemia

Epidemiology:

• Most common acute leukaemia in adults
• 3000 cases per year in the UK (cancer research UK)

Risk factors

• Age: average age of diagnosis is 68 years old
• Myelodysplasia: precursor lesion and evolves to AML in 30% of

cases

• Chemotherapy
• Radiotherapy

Myeloid AML CML Myelofibrosis Polycythaemia vera Essential thrombocytosis

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Which of the following translocations is associated with AML?

Question 2

t(9;22) t(8;14) t(12;21) t(15;17) t(14;18) app.bitemedicine.com

Q2 Q1

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

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

Definition: myeloproliferative condition. Neoplastic proliferation of

mature myeloid cells (granulocytes and their precursors)

• Immature = acute leukaemia
• Mature = chronic leukaemia

Risk factors

• Age: 65-75 years of age
• Radiation

Myeloid AML CML Myelofibrosis Polycythaemia vera Essential thrombocytosis

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Once CML is confirmed, which of the following is first-line management?

Question 3

All-trans retinoic acid Imatinib Stem cell transplant IFN alpha Hydroxyurea app.bitemedicine.com

Q1

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)

Management

• Tyrosine kinase inhibitor
• Inhibits BCR-ABL fusion product

Leukaemia Prevalence of Philadelphia chromosome CML

• 95%

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 years Progression of disease Transformation to acute leukaemia with poor prognosis

• 2/3

rd AML

• 1/3

rd ALL

Cell counts in blood <10% blast cells <20% blast cells ≥20% blast cells

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Introduction: Myelofibrosis

Definition: myeloproliferative condition. Neoplastic proliferation of

mature myeloid cells, particularly megakaryocytes

• Leading to marrow fibrosis

Risk factors

• Age: >65 years
• Radiation

Myeloid AML CML Myelofibrosis Polycythaemia vera Essential thrombocytosis

Pathophysiology: Myelofibrosis

(4)

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Which of the following is associated with myelofibrosis?

Question 4

Hypercellular bone marrow Smudge cell Teardrop red cell ‘Wet tap’ app.bitemedicine.com

Q1

Lymphoblasts

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

Definition: myeloproliferative disorder. Neoplastic proliferation of

mature myeloid cells, particularly RBCs

• Can also have thrombocytosis and granulocytosis

Risk factors

• Age: peak incidence 50-70 years of age
• Male

Myeloid AML CML Myelofibrosis Polycythaemia vera Essential thrombocytosis

Pathophysiology: Polycythaemia vera

JAK2 V617F mutation

(4)

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Clinical features

PCV

Headache Blurry vision Flushed appearance Palmar erythema Itching after a bath (release of histamine) Erythromelalgia

• Burning pain of extremities

Increased risk of thrombosis Clinical features related to hyperviscosity

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In a patient with polycythaemia vera, which of the following should be started?

Question 5

Aspirin Hydroxycarbamide (hydroxyurea) Imatinib Phenoxymethylpenicillin app.bitemedicine.com

Q1

Warfarin

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

• Definition: myeloproliferative disorder. Neoplastic proliferation
• f mature myeloid cells, particularly megakaryocytes
• Increased risk of bleeding and/or thrombosis

Risk factors

• Age: >50-70 years of age

Myeloid AML CML Myelofibrosis 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

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Recap

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Top-decile question

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References

1. Herbert L. Fred, MD and Hendrik A. van Dijk / CC BY-SA (https://creativecommons.org/licenses/by-sa/3.0) 2. A.Rad and Mikael Häggström, M.D. - Author info - Reusing imagesExample citation (in caption or footnote):- &quot;By A. Rad and M. Häggström. CC- BY-SA 3.0 license.&quot; / CC BY-SA (http://creativecommons.org/licenses/by-sa/3.0/) 3. ARad (creation of original), RexxS, Mikael Häggström and birdy and Mikael Häggström, M.D. - Author info - Reusing images / CC BY-SA (http://creativecommons.org/licenses/by-sa/3.0/) 4.

• Modified. A.Rad and Mikael Häggström, M.D. - Author info - Reusing imagesExample citation (in caption or footnote):- &quot;By A. Rad and M.

Häggström. CC-BY-SA 3.0 license.&quot; / CC BY-SA (http://creativecommons.org/licenses/by-sa/3.0/) 5. Paulo Henrique Orlandi Mourao / CC BY-SA (https://creativecommons.org/licenses/by-sa/3.0) 6. Aryn89 / CC BY-SA (https://creativecommons.org/licenses/by-sa/4.0) 7. J3D3 / CC BY-SA (https://creativecommons.org/licenses/by-sa/4.0) 8.

• Prof. Osaro Erhabor / CC0

All other images were made by BiteMedicine or under basic license from Shutterstock and not suitable for redistribution.

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