Polycythemia Vera

In oncology, polycythemia vera (PV) is an uncommon myeloproliferative neoplasm in which the bone marrow makes too many red blood cells. Approximately 98% of PV patients have a JAK2 gene mutation in their blood-forming cells (compared with 0.1-0.2% of the general population).

Most of the health concerns associated with PV, such as thrombosis, are caused by the blood being thicker as a result of the increased red blood cells.

PV may be symptomatic or asymptomatic. Possible symptoms include itching (pruritus), particularly after exposure to warm water, and severe burning pain in the hands or feet that is usually accompanied by a reddish or bluish coloration of the skin.

Treatment consists primarily of blood withdrawals (phlebotomy) and oral meds.

PV is more common in the elderly.

Signs and symptoms

Symptoms

People with PV can be asymptomatic. Symptoms of PVhttps://www.lls.org/myeloproliferative-neoplasms/polycythemia-vera/signs-and-symptoms that may aid identification include;
*pruritus (itching), particularly after exposure to warm water (such as when taking a bath), which may be due to abnormal histamine release or prostaglandin production. Such itching is present in 40%-55% of patients with PV.
*erythromelalgia, a burning pain in the hands or feet, usually accompanied by a reddish or bluish coloration of the skin. Erythromelalgia is caused by an increased platelet count or increased platelet "stickiness" (aggregation), resulting in the formation of tiny blood clots in the vessels of the extremity; it responds rapidly to treatment with aspirin.
There are many other possible symptoms of PV, including night sweats and fatigue.

No symptoms are required for diagnosis.

Other diseases that may be present with PV

Other diseases that may be present with PV include;
*Splenomegaly may cause the spleen to be palpable in some patients, which may be associated with both the V617F mutation and the development of myelofibrosis.
*Gouty arthritis may be present in up to 20% of patients.
*Peptic ulcer disease is common in patients with PV; most likely due to increased histamine from mast cells, but may be related to an increased susceptibility to infection with the ulcer-causing bacterium '' H. pylori''.

Pathophysiology

Polycythemia vera (PV), being a primary polycythemia (increase in the fraction of volume occupied by red cells in the blood), is caused by neoplastic proliferation and maturation of erythroid, megakaryocytic and granulocytic elements to produce what is referred to as panmyelosis. In contrast to secondary polycythemias, PV is associated with a low serum level of the hormone erythropoietin (EPO). Instead, PV cells often carry activating mutation in a tyrosine kinase–encoding gene, '' JAK2'', which acts in signaling pathways of the EPO receptor, making those cells proliferate independently from EPO.

Diagnosis

Diagnostic criteria

WHO 2016

Diagnostic criteria for polycythemia vera were modified by the World Health Organization in 2016. The WHO criteria for polycythemia vera are specifically outlined in Table 4.

There are 3 major criteria for PV diagnosis:
# A very high red blood cell count, which is usually identified by elevated levels of hemoglobin or hematocrit;
# A bone marrow biopsy that shows hypercellularity and abnormalities in megakaryocytes; and
# The presence of a mutation in the Janus kinase 2 (''JAK2'') gene.
A minor diagnostic feature is that patients usually have a very low level of erythropoietin, a growth factor that increases the production of red blood cells.

Reviews 2023-25

As of 2025, reviews state diagnosis can be based on
*the presence of a JAK2 mutation and
*hemoglobin/hematocrit levels of >16.5 g/dL/49% in men or 16 g/dL/48% in women.
Bone marrow morphologic confirmation is advised but not mandated.

JAK2

Approximately 98% of PV patients have a JAK2 gene mutation in their blood-forming cells (compared with 0.1-0.2% of the general population).

A mutation in the JAK2 kinase (V617F) is strongly associated with polycythemia vera. While it is a JAK2 V617F mutation in 95% of patients, ''JAK2'' exon 12 mutations have also been observed. The V617F mutation is not inherited, but develops as a somatic mutation in the erythroid progenitor cells. Some patients may lose the normal allele in the diseased cells entirely together with the short arm of chromosome 9 (9p), likely due to mitotic recombination causing copy-neutral loss of heterozygosity. While the JAK2 V617F mutation is generally sporadic (random), a certain inherited haplotype of ''JAK2'' has been associated with its development.

Outlook and prognosis

Prognosis

PV may remain stable for many years, with no effect on life expectancy, particularly if managed effectively.https://www.lls.org/myeloproliferative-neoplasms/polycythemia-vera/treatment/treatment-outcomes Studies show the median survival rate of controlled PV ranges from 10 to 20 years but most observations are of people diagnosed in their 60s. Patients live close to a normal life expectancy, but overall survival in PV is below that of age- and sex-matched general population. Factors predicting this may include age and detailed genetic differences.

Possible complications and developments

PV may cause blood clotting complications (thrombosis), with the two main risk factors being a previous clot or clots, and age (60 years or older). If PV is untreated, there is a substantial risk of Budd-Chiari syndrome (a hepatic vein thrombosis).

PV may develop into myelofibrosis (a rare bone marrow cancer) or acute myeloid leukemia.

Bleeding is a possible PV complication, although major bleeds are rare.

Treatment and management

Overview

As of 2024 a cure for PV has not been found.

The treatment goal is to prevent thrombosis. Periodic blood withdrawals (phlebotomy), to keep hematocrit level below 45%, and daily (or twice daily) aspirin (81 mg) has been called the "backbone" of treatment, regardless of risk category, if there are no contraindications.

Additional management will depend on triage into high and low risk categories.

A secondary treatment goal is to alleviate symptoms, for instance of pruritus (itching).

Blood withdrawals

Frequent blood withdrawals (phlebotomy) are one form of treatment, which often may be combined with other therapies. The removal of blood from the body induces iron deficiency, thereby decreasing the hemoglobin / hematocrit level, and reducing the risk of blood clots. Phlebotomy is typically performed to bring their hematocrit (red blood cell percentage) down below 45 for men or 42 for women. It has been observed that phlebotomy also reduces cognitive impairment.

Meds

Aspirin may be taken, to reduce thrombosis risk, regardless of risk category.

Medications are also used which reduce the number of red blood cells. These include hydroxyurea and interferon therapy, among others. The tendency of some practitioners to avoid chemotherapy if possible, especially in young patients, is a result of research indicating possible increased risk of transformation to acute myelogenous leukemia (AML). While hydroxyurea is considered a safer chemotherapy in this aspect, there is still some debate about its long-term safety.

There are indications that the lung cancer drug erlotinib may be an additional treatment option for those with certain genetic markers.

Ruxolitinib (brand name Jakafi), a Janus kinase 2 (JAK2) inhibitor, is also used to treat polycythemia.

Ropeginterferon alfa-2b (Besremi) was approved for medical use in the European Union in February 2019, and in the United States in November 2021. Ropeginterferon alfa-2b is the first medication approved by the U.S. Food and Drug Administration (FDA) to treat polycythemia vera that people can take regardless of their treatment history, and the first interferon therapy specifically approved for polycythemia vera. Interferon alfa-2b is also used.

Lifestyle

A healthy lifestyle, including no smoking and avoidance of excessive weight, is also recommended.

Specialist care

A hematologist may be involved in the care of patients with PV.

Managing itching, if present

Ideas for managing itching include trying cooler showers and baths.

Managing emotional and practical effects

Patient education and patient forums can help patients practically and emotionally manage a PV diagnosis, symptoms and other practical considerations.

Epidemiology

Polycythemia vera occurs in all age groups, although the incidence increases with age.
One study found the median age at diagnosis to be 60 years, and another that the highest incidence was in people aged 70–79 years.
10% of PV patients are below age 40 years.

Overall incidences in population studies have been 1.9/100,000 person-years in a Minnesota study, and
1.48/100,000 person-years in an age-standardized Swedish study (n = 6281). PV can impact all ethnic groups. There are slightly more cases in men than women.

A cluster around a toxic site was confirmed in northeast Pennsylvania in 2008.

Notable deaths

* Phyllis George (1949–2020), American sportscaster and former First Lady of Kentucky
* Chet Lemon (1955-2025), American baseball player
* Ron Miles (1963–2022), American jazz trumpeter
* Nell Rankin (1924–2005), American mezzo-soprano

References

External links

Polycythemia Vera
at the National Heart, Lung, and Blood Institute
*

{{Authority control

Hematopathology
Myeloid neoplasia
Rare cancers