Polycythaemia

Question 1

Define polycythaemia

Answer 1

Increase in haemoglobin concentration above the upper limit normal to age and sex

Question 2

What are the types of polycythaemia

Answer 2

Relative (lack of plasma)/ pseudopolycythaemia: alcohol, obesity, diuretics

True:
Primary (myeloproliferative neoplasm): philadelphia Chr -ve or +ve
Secondary (non-malignant)

Question 3

What are the causes of true primary polycythaemia

Answer 3

Primary (myeloproliferative neoplasm): suppressed EPO
Philadelphia Chr -ve:
- essential thrombocythaemia (megakaryocyte)
- Polycythaemia vera (erythroid)
- Primary myelofibrosis

Philadelphia chromosome +ve:
CML

Question 4

What are the causes of secondary true polcythaemia

Answer 4

Raised EPO
Appropriate (JAK2 wild type/V617F/Exon12):
- High altitude
- Hypoxic lung disease (COPD)
- Cyanotic heart disease
- High affinity Hb

Inappropriate:
- Renal disease (cysts, tumours, inflammation)
- Uterine myoma
- Other tumours (liver, lung)

Question 5

Epidemiology of polycythaemia

Answer 5

Median age of diagnosis is 61
M > F in PV
Thrombosis and thrombocytosis were more frequent in women

Question 6

Symptoms of polycythaemia

Answer 6

Asymptomatic

Symptoms caused by hyperviscosity:
- Headache
- Dizziness
- Dyspnoea
- Tinnitus
- Blurred vision
- Fatigue
- Night sweats
Symptoms of histamine release
- Pruritus after hot bath
- Peptic ulceration
Thrombosis symptoms: Calf swelling, calf pain, sudden onset SOB and chest pain

Question 7

Signs of polycythaemia on examination

Answer 7

General
- Plethoric complexion
- Scratch marks due to itching
- Conjunctival suffusion
- Retinal venous engorgement
Obs
- Hypertension
Abdominal
- Splenomegaly (75% of polycythaemia rubra vera)

Question 8

Investigations for polycythaemia

Answer 8

Sats: ? secondary poly

FBC:
- Raised Hb/Hct/red cell mass
- Reduced MCV
- PV → raised WCC/platelets
CRP/ESR
U&Es: raised urate
vit B12: raised in myeloproliferative
Erythropoietin:
- PV: reduced
- Secondary: raised
JAK2 mutation screening: +ve in PV
Isotope dilution techniques: raised cell mass (distinguish between relative and absolute)

Bone marrow biopsy: hypercellular/raised megakaryocytes/erythroid hyperplasia
Cytogenetics: differentiate from CML
CT abdo/brain: ?EPO-secreting tumours

Question 9

Management for polycythaemia vera

Answer 9

Venesection (only suitable in younger/healthy patients)
Cytoreductive therapy: less DNA synthesis in RBCs
1. Hydroxycarbamide
- Keep plts <400 x 109/L
- Keep Hct <45%
2. Interferon, Jak-2 inhibitors e.g. ruxolitinib
3. Busulfan
Aspirin 75mg daily
Gout → allopurinol
Pruritus → anti-histamines, SSRIs, interferon

Question 10

Management for secondary polycythaemia

Answer 10

Correct the underlying cause
Reduce HCT <55%

Question 11

Complications of polycythaemia

Answer 11

Myelofibrosis (30%)
Acute myeloid leukaemia (5%)
Cardiovascular: thrombosis, haemorrhage

Question 12

Prognosis for polycythaemia vera

Answer 12

Life expectancy of patients with PV is reported to be modestly reduced compared with that of the general population
Median overall survival is 15 years