Polycythaemia / Erythrocytosis

 

Erythrocytosis is an abnormally high haematocrit and haemoglobin concentration.  It can be classified as absolute erythrocytosis, when there is an increase in the total number of red blood cells in the circulation (increased red-cell mass), or apparent erythrocytosis, increased haematocrit and haemoglobin concentration with a normal red-cell mass.  Absolute erythrocytosis can be further classified as 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 increased production of erythropoietin; or idiopathic erythrocytosis, when the increased red-cell mass has no identifiable cause

Apparent erythrocytosis is a common cause for an increased haemoglobin and haematocrit concentration in people who are heavy consumers of alcohol, or those who smoke heavily, or use diuretics.  Secondary erythrocytosis, caused by conditions such as chronic pulmonary or renal disease, is more common than polycythaemia vera, which has an incident of between 0.4 and 2.8 per 100,000 per year

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When to suspect polycythaemia / erythrocytosis

Suspect erythrocytosis in people experiencing symptoms potentially caused by hyperviscosity, including:

  • Chest and abdominal pain
  • Myalgia and weakness
  • Fatigue
  • Headache — may be described as a sense of 'fullness' in the head and neck, with dizziness, and/or perspiration
  • Tinnitus
  • Blurred vision, temporary loss of vision in one or both eyes
  • Paresthesia
  • Slow mentation, sense of depersonalisation

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Additional symptoms that may indicate polycythaemia vera as the cause of erythrocytosis include:

  • Bruising
  • Pruritis, especially on contact with warm water
  • Abdominal discomfort (relating to splenomegaly)
  • Hyperhidrosis
  • Tenderness or painful burning and/or redness of fingers, palms, heels, or toes

NOTE: 10% to 15% of people with polycythaemia vera are diagnosed following an acute thrombotic event, and 2% to 8% following major haemorrhage

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Assessment

Ask about/note factors which may indicate polycythaemia vera, including:

  • Age over 40 years
  • Personal history of haemorrhage, thrombosis, or Budd-Chiari syndrome
  • Family history of polycythaemia vera

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Ask about/note factors which may indicate apparent erythrocytosis, including:

  • Obesity
  • Smoking
  • Alcohol excess
  • Hypertension
  • Use of thiazide diuretics, testosterone, or anabolic steroids

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Ask about/note factors which may underlie secondary erythrocytosis, such as:

  • Cardiac and respiratory symptoms or disease, smoking, potential exposure to carbon monoxide
  • Excessive daytime sleepiness, snoring, sleep disturbances
  • Previous renal transplantation

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Examination

  1. Note whether there is a ruddy complexion (indicative of erythrocytosis)
  2. Examine the eyes to assess whether conjunctival plethora (indicative of erythrocytosis) is present
  3. Palpate the abdomen to elicit:
    1. Splenomegaly, which can be indicative of polycythaemia vera — however, bear in mind that a palpable spleen is present in only 40% of cases
    2. Abdominal masses. Benign and malignant uterine, renal, and hepatic tumours, which may be palpable, can secrete erythropoietin, leading to secondary erythrocytosis
  4. Examine the digits, measure oxygen saturation, and listen to the chest — clubbing of digits, oxygen saturation <92% in room air, and/or abnormal heart or breath sounds may suggest secondary erythrocytosis caused by underlying cardiopulmonary disease
  5. Carry out urine dipstick analysis to identify possible renal causes of secondary erythrocytosis

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Investigations

Take blood samples (without a tourniquet if possible) for: 

  • haemoglobin
  • mean corpuscular volume (MCV)
  • haematocrit
  • white blood cell count (WBCs)
  • platelet count
  • LFTs
  • U&Es
  • e-GFR

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NOTE:  Erythrocytosis is defined as haemoglobin >185 g/L and/or haematocrit (Hct) >0.52 in a male and haemoglobin >165 g/L an/or Hct >0.48 in a female.  The results of these tests alongside clinical judgement should be used to determine which people require immediate additional testing:

  1. One-off values of Hct >0.6 (male); >0.56 (female) require additional investigations
  2. Polycythaemia vera is suggested by raised white blood cell and platelet counts in addition to high haematocrit. MCV is usually low in polycythaemia vera. LFTs are usually normal, but elevated values raise the possibility of Budd-Chiari syndrome. People exhibiting findings suggestive of polycythaemia vera should have further investigation
  3. Males with Hct >0.52, and females with Hct >0.48 with risk factors for apparent erythrocytosis, or signs and symptoms suggestive of secondary erythrocytosis, and without signs or symptoms suggestive of polycythaemia vera should be retested in two months following attempts to address apparent/secondary erythrocytosis. Repeat abnormal results should prompt additional investigations
  4. Secondary erythrocytosis may be suggested by abnormal LFTs, if there is a hepatic tumour. Abnormal renal function can indicate secondary erythrocytosis with an underlying renal cause
  5. Be aware that, in rare cases, a person (most commonly male) may present with 'masked' polycythaemia vera, where there is suggestive symptomatology or complications (such as unexplained thrombosis) but haemoglobin/haematocrit are clinically normal. In such cases, platelet counts are often elevated. Iron deficiency can also mask erythrocytosis — some cases of polycythaemia vera can therefore present with iron deficiency and a normal haemoglobin level

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Management and referral - polycythaemia vera

If polycythaemia vera is suspected, and/or the person is experiencing symptoms of hyperviscosity, refer urgently to a haematologist for treatment

Referral is also indicated for people testing negative for the JAK2 V617F mutation, with other features suggestive of a myeloproliferative disease such as:

  • high platelets and/or white count
  • enlarged spleen
  • family history of myeloproliferative disease
  • previous history of thrombosis
  • altered erythropoietin levels

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Specialist advice should also be sought if there is any uncertainty regarding the diagnosis

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For all people with polycythemia/erythrocytosis, manage cardiovascular disease risk factors, including hyperlipidaemia, diabetes, hypertension, and smoking

People with polycythaemia vera require annual follow-up which can be done in primary care to detect the 2-8% who will transform myelofibrosis or the 1-3% who will transform to acute myeloid leukaemia

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Management and referral - apparent erythrocytosis

If apparent erythrocytosis is suspected:

  1. Address factors that may lead to reduced plasma volume, including smoking, alcohol consumption, obesity, and hypertension
  2. If the person is taking a thiazide diuretic, consider switching to an alternative anti-hypertensive agent
  3. Advise that the person avoids use of testosterone supplements and anabolic steroids (if applicable)

NOTE:

  • Blood sampling should be repeated two months after these measures are implemented, to determine whether the haematocrit has normalised. If not, further tests should be carried out to rule out secondary erythrocytosis/polycythaemia vera
  • People with confirmed apparent erythrocytosis should be offered a blood test every 3-6 months in primary care, and if their haematocrit is greater than 0.45 on two consecutive occasions, the person should be referred to haematology to commence a venesection programme

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Specialist advice should also be sought if there is any uncertainty regarding the diagnosis

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For all people with polycythemia/erythrocytosis, manage cardiovascular disease risk factors, including hyperlipidaemia, diabetes, hypertension, and smoking

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Management and referral - secondary erythrocytosis

If secondary erythrocytosis is suspected, refer to an appropriate specialist to ensure optimal management of the underlying cause:

  1. Refer people with elevated erythropoietin levels without a chronic hypoxic disorder to haematology to exclude an erythropoietin-secreting malignancy or other rare causes of secondary polycythaemia
  2. Refer people with suspected cyanotic heart disease to a cardiologist
  3. Refer people with suspected hypoxic lung disease to a respiratory physician if necessary, or manage in primary care if appropriate
  4. Refer people with suspected sleep apnoea to a sleep clinic
  5. Refer people with suspected renal disease to renal services

NOTE:

  • Blood sampling should be repeated two months after any measures have been implemented to improve hypoxia (such as smoking cessation, supplemental oxygen, or continuous positive airway pressure [CPAP]) or to treat any other potentially causative conditions. If the haematocrit has not normalised, further investigation is necessary and a primary haematological disorder should be considered
  • People with confirmed secondary erythrocytosis should receive regular blood tests to monitor haematocrit levels. The target haematocrit is usually 0.54. Where this monitoring occurs in primary care, referral for venesection should be considered for people with raised haematocrit

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Specialist advice should also be sought if there is any uncertainty regarding the diagnosis

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For all people with polycythemia/erythrocytosis, manage cardiovascular disease risk factors, including hyperlipidaemia, diabetes, hypertension, and smoking

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Blood tests / Phlebotomy

If your practice does not have a practice nurse who is trained to take bloods, you can refer a patient to the Pathology Department at East Kent Hospitals for a blood test (find details here)

Alternatively, Buckland Hospital (Dover) and the Royal Victoria Hospital (Folkestone) both operate a walk-in service where no appointment is necessary, except for if the patient requires a Glucose Tolerance Test (GTT).  In the event that a GTT is required, please call 01304 222552 (for Buckland) and 01303 854484 (for Royal Victoria) to arrange a suitable appointment

Please ensure that the patient remembers to take with them their blood test form to the walk-in centres

Advice and Guidance is being made available for all specialties, and is being provided by consultant specialists at East Kent Hospitals.  To make a request or to check to if a query has been answered, you will need to log in via the electronic Referral System (eRS)

Click here for the "how to access" e-Referral Advice and Guidance Manual for instructions on how to make a request and check responses

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