Myeloproliferative Disorders/neoplasma (MPN) and Myelodysplastic syndrome (MDS)

Question 1

What are Myeloproliferative Neoplasms and Myelodysplastic Syndrome?

Answer 1

Pre-leukaemic conditions

Question 2

What are the different types of Myeloproliferative Neoplasms?

Answer 2

• Polycythaemia vera
• Essential Thrombocythaemia
• Primary myelofibrosis
• Chronic Myeloid Leukaemia

Question 3

What are Myeloproliferative neoplasms?

Answer 3

• A quantitative disorder where there is an increase in cells of the myeloid lineage

Question 4

What is Polycythaemia Vera?

Answer 4

• Myeloproliferative neoplasm
• Caused by clonal proliferation of a marrow stem cell
• Leads to increase in red cell volume often accompanied by increase in neutrophil and platelet levels

Question 5

What is the pathophysiology of Polycythemia Vera?

Answer 5

• Mutation of JAK 2 gene
• Means it is constantly activated, increasing production of RBCs even in absence of EPO
• Eventually, these excess cells die, leading to a decrease in production of cells and dysfunctioning bone marrow (stent phase)
• Stent phase is known as myelofibrosis

Question 6

What are the clinical features of Polycythaemia Vera?

Answer 6

• Fatigue
• Dizziness
• Increased sweating
• Redness in face
• Blurred vision
• Pruritis
• Splenomegaly
• Gout

=> More prone to thrombotic complications

Question 7

What are the investigations in suspected Polycythaemia Vera?

Answer 7

=> Genetic Testing
- JAK2 mutation

=> Bloods
- Decreased EPO

=> Bone Marrow Biopsy/Examination
- Signs of fibrosis

Question 8

What is the management of Polycythaemia Vera?

Answer 8

• Venesection
• Aspirin 75 mg/d
• Management of CVS risk factors

Question 9

What is Essential Thrombocythaemia?

Answer 9

• Persistent elevation of platelets for > 2 months

Question 10

What are the clinical features of Essential Thrombocythaemia?

Answer 10

=> Often asymptomatic but can present as:

• Arterial and venous thrombosis
• Haemorrhage
• Pruritis
• Gout
• Splenomegaly
• Burning sensation in hands

Question 11

What is the pathophysiology of Essential Thrombocythaemia?

Answer 11

• JAK2 mutation

Question 12

What is the management of Essential Thrombocythaemia?

Answer 12

• Aspirin 75mg daily to reduce thrombosis risk
• Hydroxycarbamide to reduce platelet count
• Interferon alpha for younger adults

Question 13

What is Primary Myelofibrosis?

Answer 13

• JAK2 mutation
• Increase in number of cells in the bone marrow, specifically megakaryocyte
• These megakaryocytes produce platelets, therefore excess platelets are initially produced
• These excess platelets release fibroblast growth factor which acts on fibroblast cells of the bone marrow
• Fibroblast cells produce connective tissue in excess leading to myelofibrosis
• Replacement of haematopoetic cells may cause pancytopenias, and enlargement of distal organs

Question 14

What are the clinical features of Primary Myelofibrosis?

Answer 14

• Fatigue
• Weight loss
• Bone pain
• Fever
• Pruritis

=> Splenomegaly in cases of when the cells deposit in other organs

Cytopenias occur (although WBC and platelet counts may be high in initial stages)

Question 15

What are the investigations in suspected Primary Myelofibrosis?

Answer 15

=> Blood smear

• TEAR DROP POIKILOCYTES
• Immature nucleated RBCs
• Immature WBCs
• Immature platelets

=> Bone Marrow Biopsy

• Fibrosis
• Rise in cell number in initial stages

Question 16

What is the management of Primary Myelofibrosis?

Answer 16

• Transfusion support
• Hydroxycarbamide
• Folic acid
• Growth factors
• JAK-2 inhibitors eg. Ruxolitinib
• Bone marrow transplantation

Question 17

What is Myelodysplastic syndrome?

Answer 17

Stem cell disorder associated with hypercellular BM, abnormal maturation of all 3 haemopoietic cell lineages with quantitative and qualitative reduction in peripheral blood cells

• Results n an increase in abnormal cell type within the bone marrow

Question 18

What are the possible causes of Myelodysplastic Syndrome?

Answer 18

• Secondary to drugs
• Chemicals
• Congenital disorders
• Association with other BM disorders

Question 19

What are the clinical features of Myelodysplastic Syndrome?

Answer 19

=> As a result of cytopenias

=> Anaemia

• Irritability
• Dizziness
• Pale skin

=> Leukopenia
- Increased risk of infections

=> Thrombocytopenia:

• Excessive bruising
• Easy bleeding

Question 20

What are the investigations in suspected Myelodysplastic Syndrome?

Answer 20

=> Bloods
- Reduced cell lineages

=> Blood smear

• Macrocytosis
• Hypogranular WBCs
• Platelet anisocytosis

=> Bone Marrow Biopsy
- Hypercellular

=> Chromosome analysis
- Cytogenetic abnormalities

Question 21

What is the management of Myelodysplastic Syndrome>

Answer 21

=> Dependant on the Revised International Prognostic Scoring System

=> Low risk patients:

• Improving blood counts through growth factors
• Transfusion
• Immunosuppressive therapy

=> High risk patients:

• Hypomethylating agents
• Chemotherapy
• Bone Marrow Transplant