The prevalence of PV is approximately 40-60 cases per 100,000 people, with median age of diagnosis around 60-65 years, though it can occur at any age. It affects men slightly more often than women.

The disease is caused by an acquired gene mutation (not usually inherited from parents) affecting the JAK-STAT signalling pathway, regulating blood cell production. About 95-97% of patients have a JAK2 V617F gene mutation, which acts like a switch stuck in the “on” position, signaling the bone marrow to keep producing blood cells regardless whether the body needs them. The remaining 3-5% of patients have a mutation in the JAK2 gene in a region designated exon 12. Environmental factors, age-related changes in blood generating cells, and other genetic events may contribute to disease development.

Many people have no symptoms (asymptomatic) and are diagnosed after routine blood testing. When symptoms do occur, they may include:

General symptoms:

• Fatigue and weakness

• Headaches

• Dizziness or vertigo

• Visual disturbances 

• Pruritus (itching), particularly after warm baths or showers (aquagenic pruritus)

• Erythromelalgia (burning pain in hands and feet with redness)

Due to hyperviscosity:

• Cognitive impairment or confusion

• Tinnitus (ringing in ears)

• Facial plethora (reddish or ruddy complexion)

Thrombotic (blood clotting) complications:

• Stroke or transient ischemic attacks

• Myocardial infarction

• Deep vein thrombosis

• Pulmonary embolism

• Budd-Chiari syndrome (hepatic vein thrombosis)

Other findings:

• Splenomegaly (enlarged spleen) in 30-40% of patients

• Hepatomegaly (enlarged liver)

• Hypertension

• Gout or gouty arthritis

• Peptic ulcer disease

• Unusual bleeding (nosebleeds or bleeding gums)

Diagnosis of polycythemia vera requires a comprehensive evaluation including:

Laboratory tests:

• Complete blood count showing elevated hemoglobin (>16.5 g/dL in men, >16 g/dL in women) and hematocrit (>49% in men, >48% in women)

• Elevated red blood cell mass

• Often elevated white blood cell count and platelet count

• Low or normal erythropoietin levels

• JAK2 genetic mutation testing (V617F or exon 12 mutations)

Bone marrow examination:

• Hypercellular marrow (panmyelosis) with proliferation of the three main blood forming cells in the marrow (increased red cells, white cells, and platelets)

PV is a chronic condition that cannot currently be cured, but it can be effectively managed. The main goal is to reduce the risk of clotting (thrombosis).

1. Phlebotomy (Therapeutic Blood Draw)

• This is the first-line treatment– blood is removed from a vein (similar to blood donation) to lower the blood volume and reduce the number of red blood cells;  the target is usually for a hematocrit level below 45%.

2. Aspirin Therapy

• Low-dose aspirin is commonly prescribed to reduce the "stickiness" of platelets and lower the risk of blood clots, heart attacks, and strokes.

3. Cytoreductive Medications

• Used for high-risk patients (those over 60 or with a history of clots) or those who cannot tolerate frequent phlebotomy.

• Hydroxyurea: A chemotherapy pill that suppresses bone marrow production.

• Interferon-alpha (e.g., Ropeginterferon alfa-2b): Stimulates the immune system to fight overactive bone marrow cells.

• Ruxolitinib (Jakafi): A JAK1/JAK2 inhibitor used in patients who do not respond to Hydroxyurea.

4.  Supportive Care

• Management of cardiovascular risk factors.

• Treatment of pruritus.

With proper treatment, patients with PV can have a near-normal life expectancy. Factors affecting the prognosis include the age at diagnosis (younger associated with better prognosis), a history of blood clots, presence of cardiovascular risk factors, abnormal leukocyte and platelet counts, and the response to therapy. Complications include thrombotic events, myelofibrosis (scarring of bone marrow over time), progression to acute myeloid leukemia (AML), bleeding and cardiovascular disease. Modern therapies, particularly JAK2 inhibitors, have improved symptom control and quality of life for PV patients.

1. Tefferi A, Barbui T. 2020. “Polycythemia vera and essential thrombocythemia: 2021 update on diagnosis, risk-stratification and management.” Am J Hematol. 95(12):1599-1613. doi: 10.1002/ajh.26008. Epub 2020 Oct 23. PMID: 32974939.

2. Arber DA, Orazi A, Hasserjian R, et al. 1016. “The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia.” Blood. 127(20):2391-2405. Blood. 2016 Jul 21;128(3):462-463. doi: 10.1182/blood-2016-06-721662. PMID: 31659364.

3. Spivak JL. 2002. “Polycythemia vera: myths, mechanisms, and management.” Blood. 100(13):4272-90. doi: 10.1182/blood-2001-12-0349. Epub 2002 Aug 8. PMID: 12393615.

4. National organization for rare disorders (NORD):  Polycythemia vera.

5. Orphanet:  Polycythemia vera.