Myeloproliferative Disorders

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

The three myeloproliferative disorders to remember are:

  • Primary myelofibrosis
  • Polycythaemia vera
  • Essential thrombocythaemia

 

Primary myelofibrosis is the result of proliferation of the hematopoietic stem cells. Polycythaemia vera is the result of proliferation of the erythroid cell line. Essential thrombocythaemia is the result of proliferation of the megakaryocytic cell line.

Proliferating Cell Line

Disease

Haematopoietic Stem Cell

Primary Myelofibrosis

Erythroid Cells

Polycythaemia Vera

Megakaryocyte

Essential Thrombocythaemia

Myeloproliferative disorders have the potential to progress and transform into acute myeloid leukaemia.

These conditions are associated with mutations in certain genes:

  • JAK2
  • MPL
  • CALR

 

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

 

Myelofibrosis

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.

 

Presentation

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)

 

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

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

Full Blood Count Findings

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).

 

Diagnosis

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.

 

Management of Primary Myelofibrosis

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.

 

Management of Polycythaemia Vera

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.

 

Management of Essential Thrombocythaemia

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

Chemotherapy can be used to control the disease.

 

Last updated April 2019
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