Polycythaemia

Question 1

What is polycythaemia?

Answer 1

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

Question 2

In what ways can you classify polycythaemia?

Answer 2

1. Relative Polycythaemia ⇒ normal red cell mass but low plasma volume
   o May be acute – due to dehydration (e.g. diuretics, burns, enteropathy, alcohol)
   o Chronic form associated with obesity, hypertension, high alcohol and tobacco intake
2. Absolute (True) Polycythaemia ⇒ increased red cell mass

Question 3

What are some causes of absolute polycythaemia?

Answer 3

1. Polycythaemia Rubra Vera – primary cause
   - In primary polycythaemia, there is excess and uncontrolled erythrocytosis that is independent of erythropoietin (EPO) levels. - Most cases of PV are associated with mutations in the JAK2 gene, leading to uncontrolled production of blood cells, especially RBCs.
   - In the majority of cases, it is due to the myeloproliferative condition polycythaemia rubra vera (PRV), which is also known as ‘primary proliferative polycythaemia’, although there are also some rare familial causes.
   - Risk Factor for Polycythaemia Vera ⇒ Budd-Chiari Syndrome
   - In 5-15% of cases, polycythaemia vera leads to acute myeloid leukaemia or myelofibrosis.
2. Secondary Polycythaemia – increase in EPO
   a. Appropriate increase in erythropoietin:
   * Due to chronic hypoxia (e.g. chronic lung disease, living at high altitude)
   * This leads to upregulation of erythropoiesis
   b. Inappropriate increase in erythropoietin:
   * Renal (carcinoma, cysts, hydronephrosis)
   * Hepatocellular carcinoma
   * Fibroids
   * Cerebellar haemangioblastoma
   * Secondary polycythaemia may be due to erythropoietin abuse by athletes

Question 4

Summarise the epidemiology of polycythaemia

Answer 4

• Annual UK incidence: 1.5/100,000
• Peak age: 45-60 yrs
• Generally a disease of middle and older age but polycythaemia can occur at any age.

Question 5

What is the pathophsyiology behind the symptoms caused by polycythaemia?

Answer 5

symptoms caused by hyperviscosity:
Elevated blood cell mass results in Hyperviscosity, which is associated with slow blood flow and an increased risk of thrombosis

Question 6

What are the presenting symptoms of polycythaemia?

Answer 6

• Headaches
• Dyspnoea
• Tinnitus
• Blurred vision
• Pruritis after hot bath
• Burning sensation in fingers and toes (erythromelalgia)
• Night sweats
• Thrombosis (DVT, stroke)
• Pain from peptic ulcer disease
• Angina
• Gout
• Choreiform movements (involuntary, random muscle movements)

Question 7

What signs of polycythaemia can be found on physical examination?

Answer 7

• Plethoric complexion (red, ruddy)
• Scratch marks from itching
• Conjunctival suffusion (redness of the conjunctiva)
• Retinal venous engorgement
• Hypertension
• Splenomegaly (in 75% of cases)
• Signs of underlying aetiology in secondary polycythaemia

Question 8

What investigations are used to diagnose/ monitor polycythaemia?

Answer 8

1. Haemoglobin → elevated and Haematocrit (percentage of red blood cells in your blood.) → elevated
2. JAK2 Gene Mutation Screen → present in polycythaemia vera
3. Platelet Count → elevated (thrombocytosis)
4. Polycythaemia Vera (Primary) → Decreased Serum Erythropoietin
5. Secondary Polycythaemia → increased serum EPO, check for EPO-secreting tumours
   - Primary = independent of EPO
   - Secondary = due to excess EPO  

Question 9

What complications may arise from polycythaemia?

Answer 9

Thrombosis, VTE, may progress to acute myeloid leukaemia or myelofibrosis, haemorrhage, pruritus 

Question 10

How is polycythaemia managed?

Answer 10

1. Phlebotomy (Venesection) → mechanical reduction in the number of RBCs
2. Antiplatelet Prophylaxis → aspirin (prevent thrombotic events secondary to Hyperviscosity)
3. Cytoreductive Therapy → medical reduction in number of RBCs
4. Polycythaemia Vera → JAK2 inhibitors (Ruxolitinib)