Myeloproliferative Disorders

Polycythaemia vera is a myeloproliferative disorder in which the abnormal bone marrow produces too many red blood cells. As a result the blood is thicker than normal. In some patients the number of white cells and platelets may also be increased.

Patients with polycythaemia present above the age of 40 and the median age at diagnosis is 60.
Many patients have no symptoms or signs, however when the number of red cells or platelets is high, patients are at high risk of blood clot formation in the brain (stroke) or heart (heart attack).

Patients may present with headaches, blurred vision, itching (often noticed after a hot bath) and plethora (when the patient’s skin may appear much redder in colour than normal).

Diagnosis

Polycythaemia may be diagnosed by a simple test. The Haematocrit or PCV (Packed cell volume) is a measurement of the proportion of the blood occupied by red blood cells. A persistently raised PCV >0.52 in males or > 0.48 in females requires additional investigations to confirm the cause of polycythaemia. Polycythaemia Vera can be distinguished from secondary causes of Polycythaemia by the presence of the JAK 2 mutation. This can be detected by a simple blood test and is present in 99% of patients with polycythaemia vera. Hence the absence of the JAK2 mutation effectively excludes polycythaemia vera.

Treatment

The simplest and most rapid way to treat polycythaemia vera is to reduce the number of red cells by venesection or phlebotomy. About one pint (half a litre) is removed at a time and the procedure is repeated as often as necessary with the target of reducing the PCV <0.45.

If the patient has progressive splenomegaly, constitutional symptoms or a raised platelet count then a more appropriate form of treatment is to use an oral chemotherapy drug such as hydroxyurea. Aspirin at a small daily dose of 75mg may also help prevent blood clots.

Approximately 10% of patients with polycythaemia may eventually go on to develop acute myeloid leukaemia, while in a similar number the condition may transform into myelofibrosis.

Essential thrombocythaemia is due to an abnormality of the platelet producing cells (megakaryocytes) in the bone marrow leading to an excessive production of platelets and a high number of platelets in the blood.

Diagnosis

The condition is most commonly diagnosed between the ages of 50 and 70, and is only diagnosed when other causes of a high platelet count have been ruled out.

Treatment

Although the majority of patients are asymptomatic most will however, require some form of treatment. This may simply be low doses of aspirin or if a patient has a very high platelet count and is at high risk of bleeding or thrombotic events then the platelet count may need to be lowered with oral chemotherapy agents such as hydroxyurea or anagrelide.

Myelofibrosis is a myeloproliferative disorder in which the bone marrow is initially over-active but then develops scar tissue (fibrosis).

Normal bone marrow has a very fine network of fibres supporting the blood forming tissues. In myelofibrosis this network is coarsened and thickened so that normal blood cell production is progressively reduced. As a result blood cell production begins to take place in the liver and spleen which become enlarged. The production of blood cells in the liver and spleen is less efficient and so patients frequently develop anaemia.

Diagnosis

Myelofibrosis is usually diagnosed following examination of a blood film which may show a leuco-erythroblastic blood film appearance with abnormally shaped red blood cells. Confirmation of the diagnosis requires a bone marrow trephine biopsy to detect the fibrous tissue and Cytogenetics analysis to exclude the presence of the Philadelphia chromosome found in chronic myeloid leukaemia (CML).

Treatment

Treatment for patients with myelofibrosis depends whether patients have symptoms or are anaemic. Patients who have severe anaemia will require regular blood transfusions. Patients with constitutional symptoms (night sweats, weight loss, itching) or progressive painful splenomegaly may be considered for chemotherapy drugs such as hydroxyurea, thalidomide or interferon. In some cases an operation to remove the spleen (splenectomy) can be helpful.

A minority of patients may be eligible for a donor stem cell transplant which is the only treatment with the potential of cure. Unfortunately most patients are too old to be considered for this treatment.