Polycythaemia

Question 1

Define polycythaemia

Answer 1

Simply = too many RBCs, shown by elevated haematocrit.

It may be:

• relative (i.e. as haematocrit is the volume percentage of RBCs then if dehydrated then can cause this)
• primary (polycythaemia rubra vera)
• secondary (i.e. due to COPD, OSA, altitude, excessive EPO)

Question 2

Primary polycythaemia results from…?

Answer 2

Clonal malignancy of a marrow stem cell - due to a JAK2 mutation in 95% of cases

Question 3

Symptoms of polycythaemia (general)

Answer 3

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.

Question 4

Symptoms of polcythaemia vera

Answer 4

Bruising.
Pruritis, especially on contact with warm water (due to increase mast cells and basophils which release histamine).
Abdominal discomfort (relating to splenomegaly as spleen normally removes RBCs and in this condition they build up).
Hyperhidrosis.
Tenderness or painful burning and/or redness of fingers, palms, heels, or toes (gout due to increased uric acid due to increased cell turnover)
More prone to strokes, MI, VTE

Question 5

What to ask in history

Answer 5

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

Relative erythrocytosis - obesity, smoking, alcohol excess, HTN, diuretics,

Secondary erythrocytosis - cardiac and respiratory symptoms or disease, smoking, potential exposure to carbon monoxide, OSA (Excessive daytime sleepiness, snoring, sleep disturbances), previous renal transplantation.

Question 6

Signs on examination

Answer 6

Ruddy complexion
Conjunctival plethora
Splenomegaly
Abdominal masses - benign and malignant uterine, renal, and hepatic tumours can secrete EPO
Clubbing of digits, oxygen saturation <92% in room air, and/or abnormal heart or breath sounds (underlying cardiopulmonary disease)

Question 7

Investigations

Answer 7

Urine dipstick (to identify renal causes of secondary)
Bloods - Hb, MCV (usually low in PV), haematocrit, WBC + platelets (also raised in PV), LFTs (think Budd-Chiari syndrome OR may have hepatic tumour), U&Es, eGFR (secondary polycythaemia due to renal cause)
Serum EPO — increased suggests secondary, decreased suggests PV
Serum ferritin — to screen for iron deficiency (can mask PV)
JAK2 V617F mutation — positive = definitive
Serum uric acid — frequently elevated in PV
Abdominal ultrasound — to detect splenomegaly

Question 8

Differentials

Answer 8

Essential thrombocythaemia

Chronic myelogenous leukaemia

Question 9

Management of PV

Answer 9

Urgent haem referral
Manage CVD risk factors
Annual follow up as can transform into myelofibrosis or acute myeloid leukaemia

IN SECONDARY CARE:
Venesection
Aspirin 75 mg daily
Pharmacological cytoreductive therapy e.g. hydroxycarbamide, interferon alfa or ruxolitinib
- used if high risk of thrombosis, platelets very high, evidence of disease progression, splenomegaly progresses, or poorly tolerant of venesection

Question 10

Management of relative erythrocytosis

Answer 10

Address factors that may lead to reduced plasma volume, including smoking, alcohol consumption, obesity, and hypertension

Review meds e.g. thiazide diuretics, testosterone, anabolic steroids

Put things in place + repeat bloods in 2 months

Manage CVD risk factors

Question 11

Management of secondary erythrocytosis

Answer 11

Refer to specialist - could be haematology, cardiology, respiratory, sleep clinic, renal
Put measures in place e.g. smoking cessation, oxygen, CPAP and repeat bloods in 2 months

Manage CVD risk factors