Polycythaemia

• Haematocrit is a blood test that measures the percentage of red blood cells in the total blood volume.
• • Erythrocytosis is an abnormally high haematocrit and haemoglobin concentration.
• Absolute erythrocytosis occurs when there is an increase in the total number of red blood cells in the circulation (increased red-cell mass). 
• • Primary erythrocytosis caused by polycythaemia vera, when the increased red-cell mass is caused by neoplastic proliferation of hematopoietic cells in the bone marrow.
  • Secondary erythrocytosis, when the increased red-cell mass is caused by an increased production of erythropoietin. Most commonly erythropoietin is increased due to a physiological response to chronic tissue hypoxia caused by chronic lung disease. Inappropriate production of erythropoietin by the kidney can occur.
  • Idiopathic erythrocytosis, when the increased red-cell mass has no identifiable cause.
• Apparent erythrocytosis is defined as increased haematocrit and haemoglobin concentration with a normal red-cell mass. It is caused by a low plasma volume which most commonly occurs in people taking thiazide diuretics, and those who are heavy smokers or heavy alcohol users.
• Erythrocytosis causes increased blood viscosity, leading to elevated risk of thrombosis and cardiovascular events.
• In polycythaemia vera the risk of haemorrhage may be increased, particularly in people with severe thrombocytosis. In a minority of people, the disease progresses to the myelofibrotic stage, where the bone marrow is replaced by dense fibrous bands of reticulin, and cytopenias are common. Rarely, progression to acute myeloid leukaemia occurs.
• To confirm a diagnosis of erythrocytosis, a blood sample (taken without a tourniquet, if possible) is required. An absolute erythrocytosis is defined as a haematocrit of more than 0.56 in women and more than 0.60 in men. Investigations may also be considered if there is an observed trend of increasing haematocrit.
• Specific clinical features of polycythaemia vera are generalized pruritus after bathing, splenomegaly, thrombocytosis, and neutrophil leukocytosis.
• • Additional tests that can confirm a diagnosis of polycythaemia vera include JAK2 V617F mutation testing, and measurement of erythropoietin levels (usually reduced in polycythaemia vera, often raised in secondary erythrocytosis).
• • Polycythaemia vera — referral to a haematologist is recommended for consideration of treatment with aspirin; venesection; and in people at high risk of thrombosis, pharmacological cytoreduction.
• Primary erythrocytosis caused by polycythaemia vera, when the increased red-cell mass is caused by neoplastic proliferation of hematopoietic cells in the bone marrow. Since these cells are capable of developing into platelets, red blood cells, and neutrophils, polycythaemia vera may also be accompanied by thrombocytosis, neutrophil leucocytosis, and splenomegaly. 
• Approximately 95% of people with polycythaemia vera have a V617F mutation in exon 14 of the JAK2 gene, encoding Janus kinase, a regulator of myeloproliferation. A further 4% have mutations in exon 12 of JAK2, and the remaining 1% have other mutations including LNK mutations.
• Primary erythrocytosis is genetic (JAK2)

  Secondary erythrocytosis is caused by chronic tissue hypoxia caused by chronic lung disease or inappropriate production of erythropoietin by the kidney in conditions such as renal artery stenosis

  Apparent erythrocytosis is caused by a reduced plasma volume and most commonly occurs in people with a high body mass index, those taking diuretics, or people who are heavy smokers or heavy consumers of alcohol.