Polycythaemia

Question 1

Define polycythaemia. What are the two types?

Answer 1

An increase in Hb concentration above the upper limit of normal for a person’s age and sex.

Classified into relative polycythaemia (normal RBC mass but reduced plasma volume) or absolute (true) polycythaemia (increased RBC mass)

Question 2

What is the aetiology of polycythaemia vera, secondary and relative polycythaemia?

Answer 2

Polycythaemia vera

• Myeloproliferative (i.e. all mature cells) neoplasm with mutations in JAK2 tyrosine kinase

Secondary polycythaemia

1. Appropriate HIGH EPO (erythropoietin) - due to chronic hypoxia (e.g. chronic lung disease) leading to upregulation of erythrogenesis
2. Inappropriate HIGH EPO -
   
   • renal (carcinoma, cyst, hydronephrosis),
   • hepatocellular carcinoma ,
   • fibroids,
   • cerebellar haemangioblastoma or
   • EPO abuse in athletes

Relative polycythaemia

1. Dehydration (e.g. diuretics)
2. Alcohol
3. Obesity

Question 3

How common is polycythaemia vera? Who is usually affected?

Answer 3

• M>F
• Peak age ~60yrs

Question 4

What are the signs and symptoms of polycythaemia?

Answer 4

• Hyperviscosity - headaches, dyspnoea, tinnitus, blurred vision; Thrombosis - DVT, stroke; Angina, gout, choreiform movements
• Histamine-release symptoms - Pruritus after hot baths, Pain from peptic ulcer disease

Signs:

• Plethoric complexion
• Scratch marks
• Conjunctival suffusion
• Retinal venous engorgement
• Hypertension
• Splenomegaly (in 75% of polycythaemia vera)
• Signs of underlying aetiology in secondary polycythaemia.

Question 5

What investigations would you do to diagnose polycythaemia?

Answer 5

Generally:

1. FBC-high Hb, high Hct, low MCV
2. BM biopsy
3. EPO level
4. Mutation testing

Polycythaemia vera

• BM trephine and biopsy
• Low serum EPO
• JAK2 mutation
• Other: High WCC, High plt

Secondary polycythaemia

• High serum EPO
• Other: Exclude chronic lung disease/hypoxia with pulse ox, ABG, CXR, ?EPO secreting tumours with abdo CT, brain MRI

Question 6

What are the complications of polycythaemia?

Answer 6

• Thrombosis
• Haemorrhage (defective plt function)
• Gout (hyperuricaemia from RBC breakdown)
• Renal calculi
• Peptic ulceration in 5-10% with polycythaemia vera

Good prognosis with management - mean survival 16years. Without treatment 1-2 years,

Question 7

What other myeloproliferative disorders cause polycythaemia?

Answer 7

1. Philadelphia chromosome -ve

• Polycythaemia vera (PV)
• Essential thrombocythaemia (ET)
• Myelofibrosis

2. Piladelphia chromosome +ve
   * Chronic myeloid leukaemia (CML)

Question 8

Name 3 causes of appropriately raised EPO.

Answer 8

Cyanotic heart disease

Hypoxic heart disease

High affinity Hb

High altitude

Question 9

What is the management of PV?

Answer 9

GOAL = reduce HCT <45% + reduce risk of thrombosis​

1. Venesection (only suitable in younger/healthy patients) - twice weekly 250-500ml
2. Hydroxycarbamide (cytoreductive therapy means less DNA synthesis in RBCs)
   
   • Keep plts <400 x 10⁹/L
   • Keep Hct <45%
3. Aspirin

In other causes you can treat the cause of raised EPO.

Question 10

What are the complications of PV?

Answer 10

• Acute leukaemia
• Myelofibrosis

Question 11

What is the prognosis with PV?

Answer 11

The most common causes of death in patients with PV are cardiovascular complications and transformation to acute myeloid leukaemia

Survival from diagnosis is 3-24yrs depending on severity of disease