Myeloproliferative disorders

Question 1

What are myeloproliferative disorders?

Answer 1

These conditions occur due to uncontrolled proliferation of a single type of stem cell. They are considered a type of bone marrow cancer.

Question 2

The three myeloproliferative disorders to remember are:

Answer 2

Primary myelofibrosis
Polycythaemia vera
Essential thrombocythaemia

Question 3

Primary myelofibrosis is the result of proliferation of the:

Answer 3

Hematopoietic stem cells.

Question 4

Polycythaemia vera is the result of proliferation of the:

Answer 4

erythroid cell line.

Question 5

Essential thrombocythaemia is the result of proliferation of the:

Answer 5

megakaryocytic cell line

Question 6

Myeloproliferative disorders have the potential to progress and transform into:

Answer 6

acute myeloid leukaemia.

Question 7

Myeloproliferative disorders are associated with mutations in certain genes:

Answer 7

JAK2
MPL
CALR

TOM TIP: Remember the JAK2 mutation for your exams. This can be the target of JAK2 inhibitors such as ruxolitinib.

Question 8

Myelofibrosis

Answer 8

Myelofibrosis can be the result of primary myelofibrosis, polycythaemia vera or essential thrombocythaemia.

Myelofibrosis is where the proliferation of the cell line leads to fibrosis of the bone marrow. The bone marrow is replaced by scar tissue. This is in response to cytokines that are released from the proliferating cells. One particular cytokine is fibroblast growth factor. This fibrosis affects the production of blood cells and can lead to anaemia and low white blood cells (leukopenia).

When the bone marrow is replaced with scar tissue the production of blood cells (haematopoiesis) starts to happen in other areas such as the liver and spleen. This is known as extramedullary haematopoiesis and can lead to hepatomegaly and splenomegaly. This can lead to portal hypertension. If it occurs around the spine it can lead to spinal cord compression.

Question 9

Presentation of myeloproliferative disorders

Answer 9

Initially, myeloproliferative disorders can be asymptomatic.

They can present systemic symptoms:

Fatigue
Weight loss
Night sweats
Fever

There may be signs and symptoms of underlying complications:

Anaemia (except in polycythaemia)
Splenomegaly (abdominal pain)
Portal hypertension (ascites, varices and abdominal pain)
Low platelets (bleeding and petechiae)
Thrombosis is common in polycythaemia and thrombocythaemia
Raised red blood cells (thrombosis and red face)
Low white blood cells (infections)

Question 10

In someone with suspected polycythaemia vera, there are three key signs on examination:

Answer 10

Conjunctival plethora (excessive redness to the conjunctiva in the eyes)
A “ruddy” complexion
Splenomegaly

Question 11

Full Blood Count Findings

Answer 11

Polycythaemia Vera:

Raised haemoglobin (more than 185g/l in men or 165g/l in women)

Primary Thrombocythaemia:

Raised platelet count (more than 600 x 109/l)

Myelofibrosis (due to primary MF or secondary to PV or ET) can give variable findings:

Anaemia
Leukocytosis or leukopenia (high or low white cell counts)
Thrombocytosis or thrombocytopenia (high or low platelet counts)

A blood film in myelofibrosis can show teardrop-shaped RBCs, varying sizes of red blood cells (poikilocytosis) and immature red and white cells (blasts).

Question 12

Diagnosis: myeloproliferative disorders

Answer 12

Bone marrow biopsy is the test of choice to establish a diagnosis. Bone marrow aspiration is usually “dry” as the bone marrow has turned to scar tissue.

Testing for the JAK2, MPL and CALR genes can help guide management.

Question 13

Management of Primary Myelofibrosis

Answer 13

Patients with mild disease with minimal symptoms might be monitored and not actively treated.

Allogeneic stem cell transplantation is potentially curative but carries risks.

Chemotherapy can help control the disease, improve symptoms and slow progression but is not curative on its own.

Supportive management of the anaemia, splenomegaly and portal hypertension.

Question 14

Management of Polycythaemia Vera

Answer 14

Venesection can be used to keep the haemoglobin in the normal range. This is the first line treatment.

Aspirin can be used to reduce the risk of developing blood clots (thrombus formation).

Chemotherapy can be used to control the disease.

Question 15

Management of Essential Thrombocythaemia

Answer 15

Aspirin can be used to reduce the risk of developing blood clots (thrombus formation).

Chemotherapy can be used to control the disease.