Polycythemia Vera (PV)

2 days ago
10 min read

Polycythemia vera can progress without obvious warning, materially increasing the risk of major clotting events. In most cases, a JAK2 mutation drives uncontrolled blood cell production, increasing red cell mass and blood viscosity, promoting thrombosis. Randomized trial data show that keeping hematocrit below 45 percent reduces cardiovascular death and major thrombosis by about half compared with higher targets, making a single threshold central to outcomes. Many patients have few specific symptoms until the first event, and for a substantial share, the initial sign is a stroke, myocardial infarction, or an atypical clot in the splanchnic veins.

Overview

What is polycythemia vera?

Polycythemia vera (PV) is a rare, chronic blood disorder in which the bone marrow produces too many red blood cells. This overproduction increases the proportion of red cells in the bloodstream, which can make the blood thicker and less able to move efficiently through blood vessels. When blood flows more slowly, circulation to tissues can be affected, and the heart may have to work harder to push blood through the body.

In the early stages, reduced blood flow and problems with small-vessel circulation can trigger symptoms such as frequent headaches, dizziness, and blurred or double vision. Some people also notice ringing in the ears, a ruddy or flushed complexion, or a sense of pressure in the head. As PV continues, additional symptoms may develop, including intense itching, especially after warm showers or baths, and episodes of nosebleeds or easy bruising. Symptoms vary widely. Some people have clear signs early on, while others are diagnosed after routine bloodwork shows elevated values.

PV can lead to serious health complications. The primary concern is an increased risk of abnormal blood clots, which can cause deep vein thrombosis, pulmonary embolism, heart attack, or stroke. PV can also contribute to problems with circulation in smaller vessels, leading to burning pain or redness in the hands or feet, tingling, or cold sensitivity. Over time, PV may progress to myelofibrosis, a condition in which scar tissue builds up in the bone marrow and blood production becomes impaired. In a smaller number of cases, PV can transform into acute myeloid leukemia.

Although PV is a long-term condition, treatments can significantly reduce risk and improve quality of life. Management typically focuses on lowering the red blood cell concentration, supporting healthier blood flow, and reducing the likelihood of clot-related events, while also addressing symptoms such as itching, headaches, and microvascular discomfort.

Polycythemia vera has been referred to by several other names, including primary polycythemia, polycythemia rubra vera, erythema, and Osler-Vaquez disease.

Clarification

Is polycythemia vera cancer?

Yes. Polycythemia vera is classified as a myeloproliferative neoplasm (MPN), which is a group of blood cancers in which the bone marrow produces excessive blood cells. In PV, the overproduction is driven by an acquired change in the marrow’s blood-forming stem cells, causing persistent, unregulated red blood cell production and, in many cases, increased white blood cells and platelets as well.

Symptoms

What are the most common symptoms of polycythemia vera?

Polycythemia vera typically develops slowly, and many people live with vague symptoms for years before the condition is recognized. Diagnosis often occurs later in adulthood, frequently in the 60s, because early signs can look like common, nonspecific problems such as persistent headaches, lightheadedness, or fatigue that feels out of proportion to daily life. Some people have few noticeable symptoms and only learn they have PV after routine bloodwork shows elevated levels.

As PV progresses and blood becomes more concentrated, symptoms may become more distinctive. Reduced blood flow through small vessels can affect the brain, eyes, skin, and extremities. In addition, increased cell turnover and inflammatory signaling can contribute to discomfort, itching, and a general sense of unwellness. Later symptoms can include the following.

Blurred vision
Dizziness
Excessive bleeding or bruising
Itchy skin, especially after a warm bath or shower
Feeling full after eating small amounts of food
Joint pain
Redness and burning or tingling sensation in your hands and feet
Ringing in your ears
Shortness of breath when you lie down
Swollen spots on your arms and legs

Some of these symptoms reflect small-vessel circulation issues, which can create burning pain, warmth, redness, tingling, or color changes in the hands and feet. Others can signal complications that require urgent attention. New one-sided leg swelling, sudden shortness of breath, chest pain, or neurological symptoms such as weakness, difficulty speaking, or sudden vision changes can indicate a blood clot and should be evaluated immediately.

Causes

What are the most common causes of polycythemia vera?

Polycythemia vera is caused by an acquired genetic mutation, meaning a change that occurs during a person’s lifetime rather than being inherited at birth. In most cases, the mutation involves the JAK2 gene, which plays a central role in regulating signals that the bone marrow receives to produce blood cells. In PV, this signaling becomes abnormally active, causing the marrow to keep making blood cells even when the body does not need them.

The process begins in a single blood-forming stem cell in the bone marrow. Once that cell acquires the mutation, it gains a growth advantage and begins producing large numbers of descendant cells carrying the same change. Over time, these abnormal cells expand and can dominate the marrow, increasing red blood cell production and often elevating white blood cell and platelet counts. As abnormal production accelerates, the blood becomes more concentrated, circulation can become impaired, and the risk of clot-related complications increases.

Complications

What complications are associated with polycythemia vera?

Polycythemia vera increases the risk of cardiovascular events and long-term bone marrow failure, with complications that range from acute clots to late-stage progression into secondary blood cancers. The dominant threat is thrombosis. PV alters blood viscosity, platelet behavior, and inflammatory signaling in ways that can promote clot formation in arteries and veins, sometimes in atypical locations. These events can present abruptly and carry permanent consequences, including stroke, myocardial infarction, pulmonary embolism, and organ damage from impaired blood flow.

Over time, PV can progress to an advanced stage in which the marrow loses its functional capacity. Clinicians often refer to this progression as the spent phase or secondary myelofibrosis. In this phase, scar tissue accumulates in the marrow, and effective blood production declines. The disease pattern can invert. Counts that were previously elevated may fall, and symptoms may shift from hyperviscosity and microvascular disturbance to fatigue, weakness, bleeding, and infection risk. This stage also reflects a higher likelihood of transformation into acute leukemia in a smaller subset of patients.

PV-associated marrow failure can lead to the following blood disorders.

Anemia: Anemia occurs when red blood cell production drops, and it can cause persistent fatigue, reduced exercise tolerance, shortness of breath with routine activity, and a general sense of depletion that does not match exertion.
Thrombocytopenia: Thrombocytopenia occurs when platelet levels fall, and it can increase bruising and bleeding, including nosebleeds, gum bleeding, heavier menstrual bleeding, or prolonged bleeding after minor cuts.
Leukopenia: Leukopenia occurs when white blood cell levels fall, and it can weaken immune defense, increasing susceptibility to infections and extending recovery time from routine illnesses.

Other possible complications include the following.

Budd-Chiari Syndrome: Budd-Chiari syndrome occurs when a clot blocks hepatic venous outflow, and it can present with right upper abdominal pain, abdominal swelling from fluid accumulation, liver enlargement, nausea, and abnormal liver tests, with progression that can be rapid without treatment.
Gout: Gout can develop because increased blood cell turnover raises uric acid levels, and it often presents as sudden, severe joint pain with redness and swelling, commonly affecting the big toe, foot, ankle, or knee.
Kidney Stones: Kidney stones can form when elevated uric acid levels promote crystal formation, and they can cause flank pain, nausea, urinary urgency, painful urination, or visible blood in the urine.
Peptic Ulcers: Peptic ulcers can occur due to increased histamine-driven acid secretion and gastrointestinal vulnerability in some patients, and they may present with burning upper abdominal pain, nausea, early satiety, or signs of bleeding, such as black stools or blood in vomit.

Diagnosis

How is polycythemia vera diagnosed?

Diagnosing polycythemia vera requires distinguishing a marrow-driven myeloproliferative neoplasm from secondary causes of elevated red blood cell levels. The workup is structured around converging evidence from symptoms, blood counts, hormone signaling, marrow morphology, and molecular findings. A clinician begins with a focused history and physical exam, looking for patterns that fit PV, including headaches, visual disturbances, heat-triggered itching, microvascular burning in the hands or feet, bleeding, and prior clotting events. The exam may also identify splenic enlargement or a plethoric complexion, both of which can accompany sustained overproduction of blood cells.

Testing commonly includes the following.

Complete Blood Count: A complete blood count defines the hematologic profile by measuring hemoglobin, hematocrit, and red blood cell concentration, along with white blood cells and platelets. PV is characterized by persistent elevation in hemoglobin and hematocrit that reflects increased red cell mass, and many patients also show leukocytosis and thrombocytosis, supporting a broader pattern of marrow overproduction.
Erythropoietin Blood Test: An erythropoietin level helps clarify whether red blood cell production is being driven internally by a clonal marrow process or externally by physiologic signaling. In PV, erythropoietin is often subnormal because the kidneys reduce hormonal stimulation in response to excess circulating red cells. An elevated erythropoietin level typically shifts the differential toward secondary polycythemia, where hypoxia, renal pathology, medications, or other drivers increase red cell production through heightened hormonal signaling.
Bone Marrow Biopsy: A bone marrow biopsy assesses cellularity and lineage expansion within the marrow. In PV, marrow findings often show hypercellularity with increased red cell precursors and frequently increased megakaryocytes, the platelet-forming lineage, consistent with a myeloproliferative process. The biopsy can also help distinguish PV from related disorders and provides baseline morphology that becomes clinically relevant if the disease evolves.
Mutation Testing: Molecular testing evaluates for the acquired genetic alteration that drives PV, most commonly involving the JAK2 gene. Identifying the mutation supports the diagnosis by confirming clonal hematopoiesis as the cause of the elevated counts, rather than a reactive increase in red blood cell production. Mutation status also strengthens diagnostic certainty when the presentation is early, atypical, or complicated by overlapping medical conditions.

Diagnosis is reached through alignment of these findings, not through any single result. The endpoint is a defensible diagnosis that clarifies the mechanism, guides risk stratification, and supports long-term management decisions.

Treatment

How is polycythemia vera treated?

Management of polycythemia vera centers on two priorities. The first is reducing thrombotic risk, because clots drive a substantial share of PV-related morbidity and mortality. The second is controlling symptom burden, which can remain significant even when laboratory values look improved. Treatment plans are individualized based on age, prior clotting history, hematocrit control, platelet and white blood cell trends, cardiovascular risk factors, medication tolerance, and disease progression. In practice, most strategies aim to lower red cell mass, maintain efficient blood flow, and blunt the inflammatory and microvascular effects that cause itching, headaches, and extremity discomfort.

Treatments could include the following.

Medications: Cytoreductive therapy is used to reduce overproduction of blood cells when phlebotomy alone is insufficient or when thrombotic risk is higher. Hydroxyurea (Droxia®) is a commonly used first-line cytoreductive agent that suppresses marrow production and helps stabilize red blood cell, platelet, and white blood cell counts. Low-dose aspirin is often used to reduce thrombotic risk and can improve microvascular symptoms by decreasing platelet activation, though it is avoided when bleeding risk is high or contraindications exist. For itching, which can be among the most disabling PV symptoms, very low doses of selective serotonin reuptake inhibitors (SSRIs) are sometimes used as symptom-directed therapy when standard measures do not provide relief.
Therapeutic Phlebotomy: Therapeutic phlebotomy lowers hematocrit by removing blood, reducing viscosity, and improving flow through both large and small vessels. It is often a foundational treatment, particularly early in the disease course. Hematocrit control is a central target for risk reduction in PV, and maintaining hematocrit below 45 percent is widely used to reduce the likelihood of thrombotic complications. Phlebotomy schedules are adjusted based on serial blood counts, symptoms, and the rate of hematocrit recovery.
Interferons: Interferons are injectable therapies that can suppress abnormal marrow activity and reduce blood counts, with the added advantage of being appropriate in certain clinical situations where other cytoreductive agents are less desirable. They can improve symptom burden and help control hematocrit and platelet levels, and they are often considered for patients who need cytoreduction but prefer an alternative to hydroxyurea or require a different risk profile.
Ruxolitinib or Jakafi: Ruxolitinib (Jakafi®) is a JAK inhibitor that targets the overactive JAK-STAT signaling pathway central to PV. By dampening this pathway, it can reduce abnormal blood cell production and improve PV-related symptoms, including itching and splenic discomfort when present. It is generally used when hydroxyurea and or interferon are ineffective, not tolerated, or cannot be used, and it can be particularly valuable when symptom control remains poor despite hematocrit management.
Stem Cell Transplant: Stem cell transplant is not a routine therapy for PV, but it may be considered in advanced or refractory disease, particularly when PV progresses to secondary myelofibrosis or transforms into acute myeloid leukemia. Because a transplant carries significant risks, including infection, graft-versus-host disease, and treatment-related complications, it is typically reserved for selected patients after specialist evaluation and careful assessment of disease trajectory, overall health, and potential benefit.

Effective PV management also includes ongoing monitoring and risk modification, including attention to blood pressure, cholesterol, diabetes, tobacco exposure, and other factors that compound clot risk. The goal is durable hematocrit control, reduced thrombotic events, and symptom relief that holds steady over time.

Outlook / Prognosis

What’s the life expectancy for someone diagnosed with polycythemia vera?

Polycythemia vera is a chronic condition with a long disease course for many patients, particularly when the primary risks are actively managed. Population studies commonly describe median survival in the range of roughly one to two decades after diagnosis, with meaningful variation driven by age at diagnosis, prior thrombosis, cardiovascular risk profile, and whether the disease progresses to myelofibrosis or transforms to acute leukemia. A large estimate frequently cited in clinical education places overall survival around 20 years after diagnosis, but that figure is best understood as a midpoint across heterogeneous patients, not a personal forecast.

Prognosis improves when hematocrit is controlled, and thrombotic risk is treated as the central clinical problem. Evidence supporting strict hematocrit control has shaped modern practice, including randomized trial data showing lower rates of cardiovascular death and major thrombosis when hematocrit is maintained below 45 percent.

Because PV behaves differently across individuals, the most accurate outlook comes from a clinician who can integrate blood count patterns, symptom burden, clot history, cardiovascular risk factors, and any evidence of disease evolution.

Management

What can I do to improve well-being?

Daily choices cannot replace medical management, but they can meaningfully reduce clot risk and support circulation, energy, and recovery. The goal is to reduce avoidable pressure on blood vessels and the heart while maintaining steady blood flow.

Stay Active: Regular movement supports circulation, reduces venous stasis, and helps counter the clotting risk that rises when blood flow slows. Consistent, moderate activity also improves sleep, mood, and stress tolerance, which matters in a chronic disease where fatigue and symptom burden can accumulate over time.
Stop Smoking: Smoking promotes vascular narrowing and endothelial injury, compounding the thrombotic environment already present in PV. Stopping reduces strain on blood vessels and improves oxygen delivery, two factors that directly intersect with PV risk biology.
Avoid High Altitudes: Higher elevations reduce ambient oxygen, which can worsen hypoxia-driven physiology and increase symptoms for some people. In PV, where circulation and oxygen delivery can already be compromised by elevated hematocrit, altitude exposure can amplify shortness of breath, headaches, and fatigue in susceptible patients.
Manage Your Weight: Weight management lowers cardiovascular risk and reduces the workload on the heart and vascular system, which is particularly relevant in a condition defined by increased clot risk. A stable, health-supporting weight also improves blood pressure, sleep quality, and mobility, all of which influence day-to-day symptom experience.
Monitor Your Blood Pressure: Hypertension increases the likelihood of cardiovascular events and can intensify vascular stress in a disease already associated with thrombosis. Routine monitoring makes risk visible early, supports timely medication adjustment when needed, and strengthens overall risk reduction alongside hematocrit control.