Polycythaemia and polycythaemia vera
- Lesion
Too many red cells: sometimes only too little plasma, sometimes a response to low oxygen, and sometimes a marrow cancer called polycythaemia vera.
What it is
Polycythaemia is a high red cell concentration. Relative polycythaemia reflects a smaller plasma volume (dehydration, diuretics, stress). Absolute polycythaemia is a true increase in red cell mass: secondary when erythropoietin is raised appropriately (hypoxia from lung disease, high altitude, cyanotic heart disease) or inappropriately (EPO-secreting tumours such as renal cell and hepatocellular carcinoma), and primary when the erythroid precursors themselves are abnormal, as in polycythaemia vera. PV is an MPN with JAK2 V617F, low erythropoietin and a high risk of thrombosis.
Structure
- PV marrow: hypercellular for age with increased erythroid, granulocytic and megakaryocytic cells; some fat remains.
- Spent phase: reticulin and collagen fibrosis, falling counts, massive spleen from extramedullary haematopoiesis.
- Organs: congestion and thrombi; bleeding from abnormal platelets.
Step by step
- PV: JAK2 V617F makes the JAK2 kinase active without a ligand.
- Erythroid progenitors proliferate with little or no EPO; EPO production falls.
- Red cell mass and viscosity rise; platelets are increased and dysfunctional.
- Sluggish flow plus abnormal platelets cause thrombosis and minor bleeding.
- Secondary forms: hypoxia stabilizes HIF in the kidney, raising EPO and red cell production.
Classifying polycythaemia
| Type | Mechanism | Examples | EPO |
|---|---|---|---|
| Relative | Low plasma volume | Dehydration, vomiting, diarrhoea, diuretics, stress (Gaisböck) | Normal |
| Secondary, appropriate | Tissue hypoxia | Chronic lung disease, high altitude, cyanotic heart disease, smoking | High |
| Secondary, inappropriate | EPO secreted without hypoxia | Renal cell carcinoma, hepatocellular carcinoma, cerebellar haemangioblastoma, renal cysts | High |
| Primary, inherited | Abnormal EPO receptor or oxygen sensing | Familial EPO receptor mutations; HIF pathway defects | Low or variable |
| Primary, neoplastic | Clonal erythroid proliferation | Polycythaemia vera (JAK2 V617F) | Low |
Markers
- JAK2 V617F
- Serum erythropoietin
- Red cell mass
Clinical notes
- PV: plethora, headache, dizziness, itching after a warm bath, gout, epistaxis; thrombosis may come before the blood changes.
- Phlebotomy and low-dose antiplatelet therapy extend survival markedly.
- People living at high altitude in the Andes have physiologically higher haemoglobin.
Test yourself
Think of the answer, then tap the question to see it.
How does the erythropoietin level differ between polycythaemia vera and secondary polycythaemia?
It is low in PV and high in secondary polycythaemia.
Which two tumours can cause secondary polycythaemia?
Renal cell carcinoma and hepatocellular carcinoma (also cerebellar haemangioblastoma).
What is the leading cause of serious morbidity in PV?
Arterial and venous thrombosis, including hepatic, portal and mesenteric veins.
Elsewhere in DurgiPedia
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Polycythemia vera: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Polycythemia vera: MedlinePlus Medical Encyclopedia (MedlinePlus, US National Library of Medicine, 2026).
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Representative model, for educational purposes only.