Myeloproliferative Disorders

Question 1

What are myeloproliferative disorders?

Answer 1

A group of conditions characterized by clonal proliferation of one or more haemopoietic component i.e. increased production of mature cells

Question 2

How are Myeloproliferative disorders grouped and which conditions are in each group?

Answer 2

Philidelphia -ve: Polycythaemia Vera, Essential Thrombocythaemia, Primary Myelofibrosis
Philidelphia +ve: Chronic Myeloid Leukaemia

Question 3

What are the Primary Causes of True Polycythaemia?

Answer 3

Polycythaemia Vera, Familial Polycythaemia

Question 4

What are the Secondary Causes of True Polycythaemia?

Answer 4

Appropriately raised EPO: high altitude, hypoxic lung disease, cyanotic heart disease, high affinity Hb
Inappropriately raised EPO: renal disease (cysts, tumours, inflammation), uterine myoma, liver and lung tumours

Question 5

What is Relative (Psuedo) Polycythaemia? what are the causes?

Answer 5

Normal RBC, but reduced plasma volume

Causes: burns, vomiting, diarrhea, smoking, diuretics, obesity (anything that ‘dries you out’)

Question 6

The main symptoms of PRV is hyperviscosity and hypervolaemia, how can this manifest clinically?

Answer 6

Blurred vision, headache, fatigue, dyspnoea, plethoric (red nose), thrombosis and stroke, retinal vein engorgement, erythromyalagia, splenomegaly

Question 7

An increase of what inflammatory substance in PRV cause aquagenic pruritis? What else can it cause?

Answer 7

Histamine.

Peptic Ulcers

Question 8

What point mutation is associated with PRV

Answer 8

JAK2 (V617F)

Question 9

What investigations should be ordered if you suspect PRV and what would a positive result show?

Answer 9

Full Blood Count: Hb, HCT, platelets, WCC, EPO
Hb and HCT will be very high, platelets and WCC can also be raised.
Low serum EPO.
NB. PRV is normally an incidental finding on routine blood checks

Question 10

What are the treatments for PRV?

Answer 10

Venesection
Hydroxycarbamide (maintenance)
Aspirin (keep platelets under 400)
Aim of treatment is to reduce the viscosity of blood

Question 11

What is myelofibrosis?

Answer 11

Myeloproliferation causes fibrosis of BM or replacement with collagenous tissue. Can be primary (idiopathic) or secondary.

Question 12

What can cause secondary myelofibrosis?

Answer 12

PRV, Essential Thrombocytopenia, leukaemia… probably other things, but these are the main 3

Question 13

What causes the splenomegaly in myeloproliferative disorders?

Answer 13

Increased haemopoesis in the BM causes it to become overrun, so the spleen and liver begin to take over haemopoesis

Question 14

What will you see on a myelofibrotic blood film?

Answer 14

Blood film: tear drop poikilocytes (dacrocytes), leukoerythroblasts (primitive cells), giant platelets, circulating megakaryocytes

Question 15

What would a myelofibrotic bone marrow biopsy show?

Answer 15

increased collagen fibrosis, prominent megakaryocyte hyperplasia and clustering with abnormalities, new bone formation

Question 16

How is a LP of someone with myelofibrosis often described?

Answer 16

“dry tap”

Question 17

What are the treatments for myelofibrosis?

Answer 17

Support with blood products
Splenectomy - for symptomatic relief
Hydroxycarbamide (cytoreductive therapy), thalidomide, steroids, SCT
New = Ruxolotinib (JAK2 inhibitor)

Question 18

What are the clinical features of Myelofibrosis?

Answer 18

hepatomegaly, massive SPLENOMEGALY, weight loss
Pancytopenia symptoms: anaemia, fatigue, easy bruising, frequent fevers etc.
Can present with Budd-Chiari Syndrome

Question 19

In which MPD do megakaryocytes dominate the BM (increased platelets)?

Answer 19

Essential Thrombocythaemia (Thrombocytosis)

Question 20

What are the clinical features of essential thrombocythaemia?

Answer 20

Venous are arterial thrombosis (stroke and MI), gangrene, and haemorrhage, erythmelalgia (red hands and feet), splenomegaly, dizziness, headaches, visual disturbances

Question 21

What would a patients blood tests, blood films and bone marrow show if they had essential thrombocythemia?

Answer 21

Platelet count over 600
Film: large platelets and megakaryocyte fragments
BM: increased megakaryocytes

Question 22

What is the treatment for ET?

Answer 22

Aspirin, Anagrelide (reduces formation of plts from megakaryocytes), Hydroxycarbamide (antimetabolite, only used if plt count is very high)

Question 23

What is the prognosis of ET?

Answer 23

Often have normal life span

Around 5% will have leukaemic transformation after 10 years.

Question 24

What is the prognosis of Myelofibrosis and what s the average age of incidence.

Answer 24

Prognosis: 3-5 years

Age of incidence: around 70yo