• Approximately 95% of patients with PV have a specific mutation known as JAK2 V617F [3].
• A smaller group (approximately 3–4%) has changes in a different part of the JAK2 gene, specifically exon 12 mutations [3].
• These mutations are acquired (develop during life), not inherited from parents.

The JAK2 mutation causes bone marrow cells to divide more frequently than they should. This leads to an excessive number of blood cells, thicker blood, and an increased risk of clots and other PV symptoms [4].

While the JAK2 mutation is the main cause, other things may influence whether PV develops:

• Age: PV is most common in individuals over the age of 60 [5].
• Environment: Research has examined radiation and chemical exposure, but no strong link has been established [6].
• Family history: Rarely, PV or related blood disorders appear in families. This may mean some people have an inherited predisposition, but PV itself is almost always an acquired disease [7].

1. A stem cell (a special type of cell that makes all blood cells) in the bone marrow develops the JAK2 mutation.
2. This mutated cell grows and multiplies at a rate that is more than usual.
3. Over time, an increasing number of cells carry the mutation.
4. The bone marrow makes too many blood cells.
5. The blood becomes thicker and slower to flow, increasing the risk of clotting [2].

This process often develops slowly, which is why many patients live with PV for years before symptoms worsen [8].

• Most cases: No. PV usually develops from acquired mutations in the JAK2 gene during a person's lifetime.
• Rare cases: Families with multiple members affected have been reported, suggesting a genetic predisposition [7].
• Difference: It's important to distinguish PV from familial or inherited polycythemia, a separate and much rarer group of disorders caused by genes that are passed down from parents, usually seen in children or young adults. These are not the same as polycythemia vera [6].

The excess blood cells from JAK2 mutations do not just make the blood thicker—they also make it more prone to clotting. Blood clots are a significant cause of illness and death in PV [9].

Patients with PV may experience:

• Deep vein thrombosis (DVT)
• Pulmonary embolism (clot in the lungs)
• Stroke
• Heart attack

This is why treatment (such as phlebotomy, aspirin, or cytoreduction) focuses on controlling blood counts and lowering clot risk [10].

1. What is the leading cause of polycythemia vera?

Almost all cases are caused by mutations in the JAK2 gene. These mutations are usually acquired during an individual's lifetime, not inherited [3].

2. Is PV genetic or hereditary?

PV is genetic in the sense that it is caused by a mutation in a gene, but it is not usually hereditary. Most people do not pass PV on to their children [7].

3. Why does PV increase the risk of blood clots?

The extra blood cells make blood thicker and more prone to clotting. The JAK2 mutation also makes platelets more “sticky,” which increases the risk of clotting [9].

4. Can lifestyle cause PV?

There is no clear evidence that diet, exercise, or environment directly causes PV. Most cases are due to acquired JAK2 mutations. However, adopting healthy lifestyle habits can help reduce the risk of clots once PV is diagnosed [6].

5. How common is PV?

PV is rare. Studies suggest an incidence of about 0.7–2.6 cases per 100,000 people each year [5].

1. Tremblay, D., Kremyanskaya, M., Mascarenhas, J., & Hoffman, R. (2024). Diagnosis and treatment of polycythemia vera: a review. JAMA.
2. Spivak, J. L. (2002). Polycythemia vera: myths, mechanisms, and management. Blood, 100(13), 4272–4290.
3. Passamonti, F. (2012). How I treat polycythemia vera. Blood, The Journal of the American Society of Hematology, 120(2), 275-284.
4. Kroll, M. H., Michaelis, L. C., & Verstovsek, S. (2015). Mechanisms of thrombogenesis in PV. Blood Rev, 29(4), 215–221.
5. Stuart, B. J., & Viera, A. J. (2004). Polycythemia vera. Am Fam Physician, 69(9), 2139–2144.
6. Tefferi, A., & Spivak, J. L. (2005). Polycythemia vera: scientific advances and current practice. Semin Hematol, 42(4), 206–220.
7. GISP (Gruppo Italiano Studio Policitemia). (1995). Polycythemia vera: natural history of 1213 patients followed for 20 years. Ann Intern Med, 123(9), 656–664.
8. Spivak, J. L. (2018). Polycythemia vera. Current treatment options in oncology, 19(2), 12.
9. Finazzi, G., & Barbui, T. (2007). How I treat patients with PV. Blood, 109(12), 5104–5111.
10. Landolfi, R., Nicolazzi, M. A., Porfidia, A., & Di Gennaro, L. (2010). Polycythemia vera. Intern Emerg Med, 5(5), 375–384.