Chronic Myeloproliferative Disorders Flashcards

1
Q

What does proliferative mean?

A

To grow or multiple by rapidly producing new tissue, parts, cells or offspring

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2
Q

Describe myeloproliferative disorders

A

Clonal haemopoietic stem cell disorders with an increased population of one or more types of haemopoietic cells

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3
Q

Is maturation depleted or preserved?

A

Preserved

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4
Q

What is BCR-ABL1 +ve?

A

Chronic myeloid leukaemia

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5
Q

What is BCR-ABL -ve?

A

Idiopathic myelofibrosis
Polycythaemia rubra vera
Essential thrombocytopenia

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6
Q

When would you consider a myeloproliferative disorder?

A
High granulocyte count
High red cell count/Hb
High platelet count
Eosinophilia/basophilia
Splenomegaly
Thrombosis in an unusual place
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7
Q

What is Chronic Myeloid Leukaemia? (CML)

A

Proliferation of myeloid cells

Granulocytes and their precursors and platelets

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8
Q

What is needed to help prevent CML from being fatal?

A

Stem cell / bone marrow transplantation in the chronic phase

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9
Q

What are the 3 phases of CML?

A

Chronic
Accelerated
Blast crisis

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10
Q

What are clinical features of CML?

A
Asymptomatic
Splenomegaly
Hypermetabolic symptoms
Gout
Problems related to hyperleucocytosis and priapism
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11
Q

What are lab features of CML?

A

Normal or reduced Hb
Leukocytosis with neutrophilia and myeloid precursors (myelocytes), eosinophilia, basophilia
thrombocytosis
Bone marow changes

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12
Q

What is the chromosome, the gene and the product which causes the abnormal phosphorylation (signalling) leading to the haematological changes seen in CML?

A
Chromosome = Philadelphia chomosome (22)
Gene = BCR-ABL1
Product = Tyrosine kinase
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13
Q

What can be used to treat CML?

A

Imatinib

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14
Q

Describe Polycthaemia rubra vera? (PRV)

A

High haemoglobin / haematocrit accompanied by arythrocytosis (a true increase in red cell mass) but can have excessive production of other lineages

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15
Q

Describe secondary polycythaemia?

A

Chronic hypoxia
Smoking
Erythropoietin-secreting tumour

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16
Q

Describe pseudopolycthaemia?

A

Dehydration
Diuretic therapy
Obesity

17
Q

What are clinical features of PRV?

A

Clinical features common to MPD?
Headache
Fatigue
Itch (aquagenic puritis)

18
Q

What happens with the Philadelphia chromosome?

A

22 and 9 swap some bits of information

Translocation

19
Q

How do you investigate polycthaemia?

A

History
Examination
FBC + film
JAK2 mutation status

20
Q

Describe JAK2?

A

It’s a kinase
Mutation present in over 95% of PRV patients
Substitution results in loss of auto-inhibition
Activation of erythropoiesis in the absence of ligand

21
Q

What are some infrequent tests for polycythaemia?

A

Erythropoietin levels

Bone marrow biopsy

22
Q

What are investigations for secondary polycythaemia?

A

CXR
O2 saturations
Arterial blood gas
Drug history

23
Q

What is the treatment for PRV?

A

Vensect to haemocrit <0.45
Aspirin
Cytotoxic oral chemo (e.g. hydroxycarbamide)

24
Q

Describe ET

A

Uncontrollable production of abnormal platelets with abnormal function
Thrombosis
Can cause bleeding due to acquired von Willebrand disease

25
What are clinical features of ET?
Common to MPD (esp. vasooclusive complications | Bleeding
26
How do you diagnose ET?
``` Exclude reactive thrombocytosis Exclude CML Genetics: JAK2 (50%) CALR (calreticulin) MPL Bone marrow appearances ```
27
How do you treat ET?
Anti-platelet agents (aspirin) | Cytoreductive therapy to control proliferation - hydroxycarbamide, anagrelide, interferon alpha
28
What can myelofibrosis be?
Idiopathic Agnogenic myeloid metaplasia Post-polycythaemia or essential thrombocythaemia
29
Describe idiopathic myelofibrosis?
``` Marrow failure Bone marrow fibrosis Extramedullary hematopoiesis Leukoerythroblastic Teardrop-shaped RBC's in peripheral blood ```
30
What are clinical features of myelofibrosis?
Marrow failure - anaemia, bleeding, infection Splenomegaly - LUQ pain, portal hypertension Hypercatabolism
31
How do you diagnose myelofibrosis?
Typical blood film (tear-drop shaped RBC and leucoerythroblastic) Fibrosis on trephine biopsy JAK2 or CALR mutation
32
What are a leucoerythroblastic film ?
Reactive (sepsis) Marrow infiltration Myelofibrosis
33
How do you treat myelofibrosis?
Supportive care (blood transfusion, antibiotics) Allogenic stem cell transplantation in select few Splenectomy JAK2 inhibitors
34
What counts as abnormal platelets?
Infection increase Iron deficiency Malignancy Blood loss