Makindo Medical Notes

• A clonal disorder of myeloid progenitor cells.
• Results in excess production of erythrocytes, platelets, and white blood cells (WBCs).
• Most cases have a mutation in the Janus Kinase 2 (JAK2) gene.
• Erythropoietin (EPO) levels are typically low.
• With appropriate treatment, mortality can be significantly reduced.

Aetiology

• Mutation in the JAK2 gene (specifically JAK2 V617F mutation) leads to constitutive activation of the JAK-STAT pathway.
• This results in hypersensitivity to growth factors like EPO and uncontrolled proliferation of myeloid cells.
• Polycythaemia Vera is classified as a myeloproliferative neoplasm.
• Characterized by chronic and progressive increase in red blood cells, white blood cells, and platelets.

Clinical Features

• Typically affects middle-aged and older adults.
• Plethora: Ruddy complexion or dusky cyanotic appearance due to increased red cell mass.
• Dizziness, headaches, visual disturbances.
• Hypertension, angina pectoris.
• Splenomegaly (70%) and hepatomegaly (50%).
• Neurological symptoms: transient ischaemic attacks (TIAs), stroke.
• Arterial or venous thrombosis (e.g., deep vein thrombosis, pulmonary embolism).
• Bleeding tendencies, especially with very high platelet counts (acquired von Willebrand disease).
• Pruritus: Itching after a hot bath or shower; may respond to antihistamines or cimetidine.
• Erythromelalgia: Burning pain and redness in extremities due to microvascular occlusion.
• Gout and hyperuricemia due to increased cell turnover.

Diagnostic Criteria

The World Health Organization (WHO) diagnostic criteria require meeting either all three major criteria or the first two major criteria and the minor criterion.

• Major Criteria:
  • 1) Hemoglobin > 16.5 g/dL in men or > 16.0 g/dL in women, or hematocrit > 49% in men or > 48% in women, or increased red cell mass.
  • 2) Bone marrow biopsy showing hypercellularity with trilineage growth (panmyelosis).
  • 3) Presence of JAK2 V617F mutation or other functionally similar mutation (e.g., JAK2 exon 12 mutation).
• Minor Criterion:
  • Subnormal serum erythropoietin (EPO) level.

Investigations

• Full Blood Count (FBC):
  • Elevated hemoglobin and hematocrit levels (Hb > 16.5 g/dL in men, > 16.0 g/dL in women).
  • Leukocytosis (WBC > 12 x 10⁹/L).
  • Thrombocytosis (platelets > 450 x 10⁹/L).
• Blood Film: May show increased cell lines but otherwise unremarkable.
• Bone Marrow Biopsy: Hypercellular marrow with trilineage (erythroid, granulocytic, megakaryocytic) proliferation.
• JAK2 Mutation Analysis: Detection of JAK2 V617F mutation.
• Erythropoietin Level: Low or suppressed serum EPO levels.
• Elevated Uric Acid Levels: Due to increased cell turnover.
• Elevated Vitamin B12 Levels: Increased binding proteins due to elevated neutrophils.
• Neutrophil Alkaline Phosphatase Score: May be elevated.
• Abdominal Ultrasound/CT Scan: To assess splenomegaly and hepatomegaly.

Differential Diagnosis

• Secondary Polycythaemia:
  • Due to hypoxia (e.g., chronic lung disease, high altitude, smoking).
  • Elevated EPO levels due to tumours secreting EPO (e.g., renal cell carcinoma, hepatocellular carcinoma).
  • Renal disorders (e.g., polycystic kidney disease, hydronephrosis).
• Relative Polycythaemia:
  • Due to decreased plasma volume (e.g., dehydration, diuretics).

Complications

• Transformation to myelofibrosis (post-polycythaemic myelofibrosis).
• Progression to acute myeloid leukemia (AML) in a minority of cases.
• Thrombotic events (arterial and venous thrombosis).
• Hemorrhagic complications due to acquired von Willebrand disease.
• Gout and nephrolithiasis due to hyperuricemia.

Management

• Phlebotomy (Venesection): First-line treatment to reduce hematocrit to < 45% in men and < 42% in women.
• Low-dose Aspirin (75–100 mg daily): To reduce thrombotic risk unless contraindicated.
• Cytoreductive Therapy:
  • Hydroxyurea (hydroxycarbamide) is the first-choice cytoreductive agent.
  • Interferon-alpha may be used, especially in younger patients or during pregnancy.
  • Anagrelide can be used to reduce platelet count if necessary.
• Allopurinol: To manage hyperuricemia and prevent gout.
• Management of Pruritus: Antihistamines, selective serotonin reuptake inhibitors (SSRIs), or interferon-alpha may help.
• Avoid Iron Supplements: Unless iron deficiency is confirmed and symptomatic, as iron can fuel erythropoiesis.
• Patient Education: Lifestyle modifications, smoking cessation, and awareness of symptoms requiring prompt medical attention.

References

• NICE Guideline NG35: Myeloproliferative Neoplasms
• Blood Journal: Polycythemia Vera
• Cancer Research UK: Polycythaemia Vera