Myeloproliferative neoplasms (MPNs), previously called Myeloproliferative diseases, are disorders of the blood, where there is uncontrolled expansion of myeloid type blood cells.
The constituents of blood are created from haemopoietic stem cells that divide asymmetrically to form myeloid and lymphoid progenitors as well as more haemopoietic stem cells. In myeloproliferative disorders, the disorder is with myeloid progenitor cells, whereby they give rise to too many daughter cells. They can be classified into different diseases depending on which cell predominates.
Although myeloproliferative disorders are a collection of neoplastic disorders, they are not malignant but rather pre-malignant, with a significant proportion transforming into acute or chronic leukaemias.
MPNs are classified into 4 different groups:
NB there are other less common MPNs – Mastocytosis, Chronic neutrophilic leukaemia and chronic eosinophilic leukaemia; but they are so rare they are beyond the scope of this article
PV is the opposite of anaemia. Patients have an increase in total red cell mass, and as a result have elevated Hb on blood tests. They may also have concomitant increase in both WCC and platelet count as a result of increased clonal expansion of myeloid progenitor cells.
Patients are most likely diagnosed incidentally, as PV is asymptomatic in its earlier stages. As the amount of red cell mass increases however, patients start to exhibit symptoms of hyperviscosity:
Pruritus (classically after having a hot bath), night sweats, weight loss, weakness and bone pain.
They may also have signs of extramedullary haemopoiesis, such as splenomegally.
95% of patients have the JAK2 V617F mutation, a mutation that is common to all non-BCR-ABL MPNs. Although the pathogenesis of all MPNs is not fully understood, it is thought that the JAK-STAT signalling pathway is key. This pathway is involved in controlling the proliferation of myeloid progenitors as well as erythropoiesis and lymphopoiesis. An excellent more detailed description of the role of JAK signalling in MPNs can be found here: http://www.areampn.com/index.jsp
Patients with PV (just as those with ET) do not have a significantly altered life expectancy, and therefore treatment is based largely upon reducing the risk of thrombosis and managing symptoms.
Venesection (phlebotomy) is still the treatment of choice alongside low dose aspirin (75mg).
Essential thrombocythaemia is characterised by a sustained increase in platelet count > 450 x 109/L. It is caused by megakaryocyte proliferation leading to overproduction of platelets.
Approximately 50% of patients have a JAK2 mutation. In those with the mutation, they often have higher Hb and WCC.
Most often ET is an incidental diagnosis where a patient is noticed to have persistent thrombocytosis despite no clear precipitant eg inflammation/infection. In a small number of cases it is diagnosed following thrombosis.
Diagnosis is made by exclusion:
No pre-existing myeloid malignancy, MPN or myelodysplastic syndrome.
No reactive cause of thrombocytosis such as haemorrhage, chronic iron deficiency, infection, malignancy, connective tissue disease, splenectomy.
A bone marrow trephine may sometimes be required to confirm the diagnosis.
Low risk: Low dose aspirin in most cases
High risk: Hydroxycarbamide (aka. hydroxyurea) is most commonly used treatment, but has side effects of causing skin ulceration or pigmentation.
Anagrelide can be used instead of aspirin as a platelet inhibitor in high risk patients. It has potentially more side effects and a possible increased risk of transformation into myelofibrosis.
Often stable for 10-20yrs may transform to myelofibrosis. 5% risk of transforming to acute leukaemia.
Primary myelofibrosis is a condition where the rapid turnover of haemopoietic stem cells leads to the progressive fibrosis of the bone marrow, changing it from a regenerative environment to a baron hypocellular structure. As a result the body adapts and regresses back to using extramedullary organs such as the liver and spleen as sites of secondary haemopoiesis.
Most patients present with:
Acknowledgements and further reading:
Hoffbrand and Moss. Essential Haematology - 6th edition. 2011.
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