MYELOPROLIFERATIVE DISORDERS

Question 1

What are the classic myeloproliferative disorders?

Answer 1

Non cancer:
Polycythaemia vera
Essential thrombocythaemia

Cancer:
Idiopathic myelofibrosis
(CML)

Question 2

What defines polycythaemia?

Answer 2

Raised PCV (packed cell volume)

Question 3

What are the causes of polycythaemia?

Answer 3

Primary
Polycytheamia vera
Familial (eg Chuvash polycythaemia)

Secondary
Chronic tissue hypoxia (eg COPD)
Ectopic EPO (eg renal disease or extrarenal neoplasms)
Endocrine causes (exogenous EPO and steroids, or endogenous syndromes such as Conn’s and Cushing’s)

Question 4

What is the term used to describe a rise in packed cell volume without a rise in red cell mass and what is it caused by?

Answer 4

Apparent polycythaemia caused by a reduction in plasma volume

Question 5

How might someone with suspected polycythaemia vera present?

Answer 5

History of occlusive vascular lesions (eg stroke, TIA, venous thrombosis)
Headache
Mental clouding
Facial redness
Itching
Abnormal bleeding
Gout

Question 6

What investigations should be ordered for someone with suspected polycythaemia vera?

Answer 6

FBC
Red cell mass
Serum ferritin
Ultrasound to assess size of spleen
Investigations into causes of secondary polycythaemia such as EPO levels
Bone marrow cytogenic analysis

Question 7

What would the full blood count of someone with polycythaemia vera show?

Answer 7

Raised WCC
Raised platelet
Raised PCV

Question 8

Why is it useful to do a serum ferritin in someone with a normal PCV but in whom there are suspicions of polycythaemia?

Answer 8

Iron deficiency may mask raised PCV

Question 9

How is someone with polycythaemia vera treated?

Answer 9

Repeated venesection to maintain PCV at less than 0.45
Low dose aspirin
Hydroxyurea or interferon-alpha can be used to maintain lower platelet count

Question 10

How often is venesection performed in someone with polycythaemia vera?

Answer 10

Quite frequently at first but eventually every 6-10 weeks

Question 11

What is the prognosis for someone diagnosed with polycythaemia vera?

Answer 11

Usually good

20% incidence of transformation to myelofibrosis and 5% to acute leukaemia

Question 12

How is apparent polycythaemia treated?

Answer 12

Venesection only done in patients with increased risk of vascular complications for other reasons.

Question 13

What is the central diagnosis feature of essential thrombocythaemia?

Answer 13

A persisting platelet count of more than 600x10^9/L

Question 14

What are the causes of a rapid increase in platelet count?

Answer 14

Reactive thrombocytosis:
Infection
Malignancy
Inflammatory diseases
Haemorrhage
Iron deficiency
Post-surgery
Post-splenectomy
Myeloproliferative disorders 
CML

Question 15

What is the genetic mutation associated with the myeloproliferative disorders?

Answer 15

JAK2 V617F

Question 16

What investigations should be performed in someone with suspected essential thrombocythaemia?

Answer 16

JAK2 V617F mutation
FBC 
Blood film 
ESR
CRP
Serum ferritin
Bone marrow aspirate
Trephine (bone marrow) histology

Question 17

What might be seen in trephine (bone marrow) histology of someone with essential thrombocythaemia?

Answer 17

Clusters of large megakaryocytes

Question 18

How might someone with essential thrombocythaemia present?

Answer 18

Microvascular occlusive events
Burning pain in extremities
Digital ischaemia
Major vascular occlusive events
Stroke
MI
Bleeding

Question 19

What can essential thrombocythaemia transform into in a minority of patients?

Answer 19

Myelofibrosis

Acute leukaemia

Question 20

How are patients with essential thrombocythaemia treated?

Answer 20

Daily low dose of aspirin
Hydroxyurea
Busulfan
Interferon-alpha (particularly useful in pregnancy)

Question 21

What are the main features of idiopathic myelofibrosis?

Answer 21

Bone marrow fibrosis - replaced with reticulin
Extramedullary haemopoiesis - liver and spleen
Splenomegaly
Leucoerythroblastic picture (immature red and white blood cells)

Question 22

How do patients with idiopathic myelofibrosis usually present?

Answer 22

Splenomegaly
Anaemia
Fatigue
Bleeding

Constitutional B symptoms may be present

Question 23

Other than idiopathic myelofibrosis, what might cause a leucoerythroblastic blood film picture?

Answer 23

Bone marrow infiltration
Severe sepsis
Severe haemolysis
Sick neonate
Administration of haemopoietic growth factors
Acute or chronic leukaemia

Question 24

What are the two phases of idiopathic myelofibrosis and what might an FBC in each phase show?

Answer 24

Proliferative phase - normal RCC or even raised, raised WCC, raised platelets
Cytopenic phase - reduced FBC

Question 25

What is the median survival of symptomatic idiopathic myelofibrosis patients?

Answer 25

3 years

Question 26

What are the treatment options for someone diagnosed with idiopathic myelofibrosis?

Answer 26

Bone marrow transplantation from a match. This cannot be performed in most patients (esp those over 50) due to the toxicity of the procedure
Supportive treatment such as blood transfusions are frequently given
Antifibrotic agents such as thalidomide may be given with varying success
Splenectomy may improve quality of life but not prognosis, by reducing need for transfusions
JAK2 inhibitors

Question 27

Why might splenectomy be useful in improving quality of life of idiopathic myelofibrosis patients?

Answer 27

Reduce need for transfusions

Question 28

What is the cause of death in people with idiopathic myelofibrosis?

Answer 28

Haemorrhage
Infection
Transformation to acute leukaemia
Iron overload from blood transfusions