Myeloproliferative disorders

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Myeloproliferative disorders are diseases where one type of myeloid cell is produced excessively.

See this link re what is the difference between myeloproliferative disorders and lukaemias?
https://www.pathologystudent.com/?p=2153


 Primary thrombocythaemia (essential thrombocythaemia)

  • Involves clonal proliferation of the megakaryocyte line of cells leading to a raised platelet level. 
  • Most commonly presents after 50 but may occur at any age. In the younger age groups, it is more common in women than men. 
  • May present as abnormal thrombosis or bleeding, or may be asymptotic (up to 50%) and be found incidentally on routine blood tests. Neurological symptoms from microthrombosis (paraesthesia/burning pain) or signs from arterial /venous thrombosis. 
  • Splenomegaly and/or hepatomegaly may be present in some patients
  • Differentials : other haematological conditions may also caused a raised platelet count, and platelet count may be acutely raised secondary to some conditions such as infection. 
  • Diagnosis is made by excluding other causes, possible investigations include FBC, bone marrow aspiration, red cell mass, clotting, chest x ray to look for undiagnosed malignancy and abdo uss to look at spleen. JAK-2 gene may be present. 
  • Primary thrombocythaemia is treated with drugs including hydroxycarbamide, a-interferon, or anagrelide to reduce platelet levels. Aspirin is also given to reduce thrombosis risk. 
  • Complications include the development of von willebrand's disease, splenic atrophy due to multiple micro infarcts
  • Survival is normal

Primary polycythaemia (polycythaemia rubra vera) 
  • proliferative disorder leading to abnormal increase in red blood cells, which may be associated with an increase in neutrophils and platelets. 
  • Occurs when erythrocyte precursors become inappropriately sensitive to insulin like growth factor and or interleukin 3, causing erythropoeisis without erythropoietin. Many patients also accquire a JAK 2 gene. 
  • Presents after the age of 40 over a long period
  • Usually presents with symptoms of hyperviscosity and occlusion - eg. headache, dizziness, stroke, 
  • On examination patient may be plethroric, and have splenomegaly and hepatomegaly. 
  • Investigations may show a increased packed cell volume (haematocrit), red cell mass, haemoglobin, and red cell count. It may also present with raised neutrophils and platelets. 
  • Serum EPO may be reduced and there may be hyperplasia of erythroid, granulocytic and megakaryocytic cells in marrow aspirates. 
  • Plasma urate and neutrophil alkaline phosphatase may be raised
  • Treatment- polycythaemia rubra vera is treated with venesection to reduce red blood cell limits. Aspirin is also given to reduce thrombosis risk
  • Chemotherapy or radiotherapy (with hydroxycarbamide or 32p) may be offered to patients with increased thrombotic risk, although radiotherapy may increase risk of malignant transformation
  • Prognosis is mostly good with 50% survival of 10 years, complications include thrombosis and development into acute leukaemia or myelofibrosis. Death is mostly from thrombosis and leukaemic transformation. 

 Myelofibrosis
  • caused by clonal proliferation of pluripotent stem cells leading to fibrosis in the marrow. 
  • Occurs in middle aged and older patients
  • Presents with constituitional symptoms such as weight loss, night sweats, fever, anaemia symptoms and splenomegaly (tenderness due to size) 
  • Spleen and liver may be enlarged due to metaplasia (so they start producing blood cells) 
  • FBC often shows low red cells, high white cell count and high platelet levels. 
  • Blood film may further show granulocyte precursor cells, nucleated red blood cell precursors, and tear drop erythrocytes (poikilocytosis) which is diagnostic. 
  • Treatment is primarily supportive with transfusions, splenectomy and splenic irradiation may sometimes help, and chemothreapy with hydroxycarbamide or a interferone 2b can slow or reverse fibrosis. 
  • Median survival is 5 years
  • 10% will transform into acute myeloblastic leukaemia. 

 Chronic myeloid leukaemia
  • causes progressive accumulation of mature myeloid cells in the blood and bone marrow. 
  • Peak presentation is at 40-60 years, and it is slightly more common in men
  • Presentation may be incidental or present with constitutional symptoms (malaise, weight loss, sweats). 
  • High leucocyte levels (leukostasis) can also impair blood flow and cause hypoxaemia in areas, this may lead to neurological symptoms such as headaches, TIAs, confusion and changes in vision, or frequently respiratory symptoms such as dyspnea. 
  • the phildelphia gene is pathognomonic of CML. The gene causes the fusion of 2 other genes which produces abnormal tyrosine kinase, which has a major role in the development of the disease. 
  • CML has 3 phases, chronic, accelerated and blast crisis (AML/ALL) 
  • The chronic phase of CML is treated with tyrosine kinase inhibitors first line (imatinib) which provides good remission rates
  • Bone marrow transplants may also produce cure, but is a high risk treatment, and may be more appropriate in younger patients
  • As Imatinib is quite new, survival rates with patients on the drug is unclear but 65% remain in remission after 10 years. 
  • Positive prognostic factors include youth, small spleen at presentation, and low white cell count at presentation. 
http://www.patient.co.uk/doctor/Thrombocytosis.htm
http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/hematology-oncology/oncologic-emergencies/
Gargani Y, Crash course haematology and immunology, 4th ed. 2012, Edinburgh, Mosby Elsevier

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