Polycythaemia vera

• Polycythaemia vera:

  • Myeloproliferative disorder
  • Excess production of erythrocytes
  • Most commonly caused by a genetic mutation in the JAK2 gene
• Pathophysiology:

  • Excess production of myeloid cells - erythrocytes, platelets or granulocytes (neutrophils, eosinophils and basophils)
  • Excess blood cells resulting in a raised haemoglobin concentration and haematocrit = polycythaemia
  • primary polycythaemia
• Secondary polycythaemia:

  • Higher number of erythrocytes are produced in a physiological response to chronic hypoxia
  • Secondary to smoking or chronic lung disease
  • Local renal hypoxia e.g. renal artery stenosis
  • Excess erythropoietin production e.g. secondary to EPO secreting tumours
• Risk factors:

  • Advancing age - median age is 60-70
  • History of Budd-Chiari syndrome - usually have JAK2 mutation
• Symptoms:

  • Headaches - usually associated with dizziness and sweating
  • Myalgia and weakness
  • Fatigue
  • Tinnitus
  • Pruritis - particularly after a hot shower or bath
  • Erythromelalgia - burning pain, warmth and redness in the hands and feet
  • Temporary loss of vision due to hyper-viscosity
  • Dyspepsia - peptic ulceration
  • Gout
• A third of patients first present due to thrombosis:

  • Stroke
  • MI
  • DVT
  • PE
  • Budd-Chiari syndrome
  • 75% of thromboses are arterial
• Typical clinical findings of polycythaemia vera include

  • A ‘ruddy’ (reddish) complexion
  • Splenomegaly: present in one-third of patients at the time of diagnosis
  • Abdominal masses: benign and malignant uterine, renal and hepatic tumours which can secrete EPO may be palpable
  • Hypertension
• Polycythaemia is defined as:

  • Haemoglobin (Hb) >185 g/L and/or haematocrit (Hct) > 0.52 in males
  • Hb >165 g/L and/or Hct > 0.48 in females
  • Red cell mass >25% above predicted
• If the patient is dehydrated, apparent polycythaemia may be present in which the Hb/Hct is raised because of a reduced plasma volume. These patients will have a normal red cell mass
• Patients often also have raised neutrophils and platelets
• Lab investigations:

  • Blood film - assess for features of leukaemia
  • U&Es and LFTs - renal or hepatic causes of secondary polycythaemia or complications of polycythaemia vera
  • Serum ferritin - low in polycythaemia vera
  • ABG
  • Serum erythropoietin - low levels suggest polycythaemia
  • JAK2 mutation analysis
• A bone marrow biopsy may be helpful in distinguishing polycythaemia vera from secondary polycythaemia.
• Imaging:

  • Abdominal ultrasound: to assess for splenomegaly and exclude secondary causes of polycythaemia including renal and hepatic pathology.
  • Further imaging: CT head/neck/chest/abdomen/pelvis looking for rarer tumours which may secrete EPO. This is not always required if a cause for the polycythaemia is found with the above initial tests. 
• Management:

  • Venesection to keep haemoglobin in normal range
  • Aspirin to reduce the risk of thrombus formation
  • Chemotherapy - hydroxycarbamide
• Complications:

  • Ischaemic stroke
  • MI
  • PE
  • Progression to myelofibrosis or AML
  • Haemorrhage - GI
  • Budd-Chiari syndrome
• The median survival is approximately 14 years. Mortality is commonly related to thromboembolic events (ischaemic stroke and myocardial infarction)
• Polycythaemia vera can result in myelofibrosis - fibrosis of the bone marrow:

  • Leads to pancytopenia
  • Extramedullary haemotopoiesis occurs - hepatosplenomegaly
  • Blood film - tear drop shaped red blood cells, anisocytosis (varying sizes of red blood cells) and blasts