Polycythaemia is an increase in red blood cell (RBC) mass, often associated with elevated haemoglobin and haematocrit levels. It can be primary, secondary, or relative. Understanding its causes and management is important for the UKMLA.

Types:

1. Absolute Polycythaemia:
   • Primary:
     • Caused by intrinsic bone marrow disorders, such as polycythaemia vera (PV).
   • Secondary:
     • Driven by increased erythropoietin (EPO) production due to hypoxia or other factors.
2. Relative Polycythaemia:
   • Due to reduced plasma volume (e.g., dehydration, diuretics).

Aetiology:

1. Primary Polycythaemia:
   • Polycythaemia Vera:
     • Chronic myeloproliferative disorder caused by JAK2 mutation.
2. Secondary Polycythaemia:
   • Hypoxia-Driven:
     • Chronic obstructive pulmonary disease (COPD), obstructive sleep apnoea (OSA), high-altitude living.
   • Non-Hypoxic Causes:
     • EPO-secreting tumours (e.g., renal cell carcinoma, hepatocellular carcinoma).
     • Exogenous EPO use (e.g., in athletes).
3. Relative Polycythaemia:
   • Dehydration, diuretic use, stress polycythaemia (Gaisböck syndrome).

Pathophysiology:

• Increased RBC mass leads to hyperviscosity, impairing microvascular flow and increasing the risk of thrombosis.
• In polycythaemia vera, clonal proliferation of RBCs, WBCs, and platelets occurs due to JAK2 mutation.

Clinical Features:

1. General Symptoms:
   • Fatigue, headache, dizziness, blurred vision, pruritus (especially after a hot shower in PV).
2. Specific Signs:
   • Thrombotic Events: Deep vein thrombosis (DVT), pulmonary embolism (PE), myocardial infarction (MI), stroke.
   • Splenomegaly: More common in PV.
   • Facial Plethora: Redness of the face.
   • Hypertension: Often present in PV.
3. Symptoms of Secondary Causes:
   • Features of underlying hypoxia (e.g., cyanosis in COPD, daytime somnolence in OSA).

Investigations:

1. Initial Tests:
   • Full Blood Count (FBC): Raised haemoglobin and haematocrit.
   • Blood Film: Often normal in secondary polycythaemia.
2. Erythropoietin (EPO) Levels:
   • Low in PV (due to negative feedback).
   • High in secondary polycythaemia.
3. JAK2 Mutation Testing:
   • Positive in ~95% of PV cases.
4. Arterial Blood Gas (ABG):
   • To assess hypoxia or hypercapnia in secondary causes.
5. Imaging:
   • Ultrasound of the abdomen for renal tumours.
   • Sleep study for obstructive sleep apnoea.

Management:

1. Primary Polycythaemia (PV):
   • Venesection:
     • First-line to reduce haematocrit to <45%.
   • Aspirin:
     • Low-dose for thrombotic risk reduction.
   • Cytoreductive Therapy (if high-risk):
     • Hydroxycarbamide: First-line.
     • Interferon-alpha: For younger patients or those intolerant to hydroxycarbamide.
2. Secondary Polycythaemia:
   • Treat the underlying cause (e.g., oxygen therapy for hypoxia, manage tumours).
3. Relative Polycythaemia:
   • Address dehydration or remove diuretics if appropriate.

Complications:

1. Thrombotic Events:
   • Increased risk of DVT, PE, stroke, or MI.
2. Haemorrhagic Events:
   • Paradoxical bleeding risk due to platelet dysfunction in PV.
3. Progression to Myelofibrosis or Acute Leukaemia:
   • Long-term risk in polycythaemia vera.

Prognosis:

• Good with appropriate management in PV.
• Poorer prognosis in untreated or advanced cases (e.g., progression to myelofibrosis).

Key Exam Points for UKMLA:

1. Diagnosis:
   • Differentiate between primary, secondary, and relative polycythaemia using JAK2 mutation testing and EPO levels.
2. Management:
   • Venesection and aspirin are first-line for PV; treat underlying causes for secondary polycythaemia.
3. Complications:
   • Focus on thrombotic events and long-term progression risks in PV.
4. Investigations:
   • EPO levels and JAK2 mutation testing are key diagnostic tools.