Polycythaemia vera is a chronic blood cancer that causes the body to produce too many red blood cells, making the blood thicker and slower than it should be. While there is no cure for this condition, modern medicine offers a range of treatments that help people manage symptoms, reduce the risk of dangerous complications like blood clots, and maintain a good quality of life for many years.

Understanding Treatment Goals in Polycythaemia Vera

When someone is diagnosed with polycythaemia vera, the main aim of treatment is not to eliminate the disease completely, but rather to control its effects on the body. The condition develops slowly and causes the bone marrow to overproduce red blood cells, which leads to blood becoming thick and sluggish. This thickness is the source of most problems, particularly the risk of blood clots, which can lead to serious events such as heart attacks, strokes, or clots in the legs and lungs.^[1][2]

Treatment approaches are tailored to each individual, depending on several factors including age, overall health, previous medical history, and the presence of symptoms. Doctors follow guidelines from medical societies that have been developed based on years of research and clinical experience. The cornerstone of managing polycythaemia vera involves reducing the number of red blood cells to keep the blood at a healthy thickness, typically measured by a value called hematocrit, which should be kept below 45%.^[4]

Beyond standard treatments that have been used for decades, there is also ongoing research into new therapies. Scientists and doctors are testing innovative medicines in clinical trials—carefully controlled studies that evaluate whether new treatments are safe and effective. These trials offer hope for better ways to manage the condition, reduce side effects, and improve the daily lives of people living with polycythaemia vera.^[14]

Standard Treatment Approaches

Blood Withdrawals: The Foundation of Treatment

The most common and longest-standing treatment for polycythaemia vera is a procedure called phlebotomy. This is essentially the same process used when someone donates blood. A needle is inserted into a vein, usually in the arm, and blood is drawn out to reduce the total volume and thickness of blood in the body. Each session typically removes about one pint of blood.^[4][9]

The frequency of phlebotomy varies from person to person. Some people may need it weekly at first, until their red blood cell count drops to a safe level. After that, the treatment continues as needed—perhaps every few months—to keep the hematocrit below 45%. While phlebotomy is simple and effective, it does have downsides. Many people experience debilitating fatigue, brain fog, and a general feeling of tiredness after repeated blood draws. The need to visit a doctor’s office regularly for the procedure can also be time-consuming and disrupt daily life.^[14]

Medications to Reduce Blood Cell Production

When phlebotomy alone is not enough, or when other blood cell counts (white blood cells or platelets) are also too high, doctors may prescribe medications to slow down blood cell production in the bone marrow. The most commonly used medicine is hydroxyurea, which is a type of chemotherapy drug taken in pill form. It works by reducing the activity of the bone marrow, thereby decreasing the number of red blood cells, white blood cells, and platelets produced.^[4][9]

Hydroxyurea is generally well tolerated, but like all medications, it can cause side effects. Some people experience low blood counts of other types, skin changes, or gastrointestinal symptoms. Regular blood tests are necessary to monitor how well the medicine is working and to watch for any unwanted effects.

Another medication that may be prescribed is interferon, a substance that occurs naturally in the body and helps regulate the immune system. Interferon can lower blood counts and may be especially useful in younger patients or during pregnancy, when other treatments may not be suitable. Interferon is given as an injection, and its side effects can include flu-like symptoms, fatigue, and mood changes.^[4]

For patients who do not respond well to hydroxyurea or cannot tolerate it, another option is ruxolitinib, sold under the brand name Jakafi. This drug is a JAK2 inhibitor, meaning it blocks the action of the JAK2 protein, which is abnormal in nearly all people with polycythaemia vera. Ruxolitinib can reduce the need for phlebotomy and also shrink an enlarged spleen, which is a common complication of the disease. Side effects of ruxolitinib may include increased risk of infections, anemia, and bruising.^[4]

Aspirin to Prevent Blood Clots

Because the thickened blood in polycythaemia vera significantly increases the risk of blood clots, many patients are advised to take low-dose aspirin daily. Aspirin works by making platelets less sticky, which reduces the chance of clots forming. However, aspirin also increases the risk of bleeding, particularly in the stomach, so it is not suitable for everyone. Your doctor will assess your individual risk and benefits before recommending aspirin.^[4][9]

Managing Symptoms and Secondary Conditions

Polycythaemia vera can cause a range of uncomfortable symptoms beyond the blood cell overproduction. Many people experience intense itching, especially after taking a warm bath or shower. This is thought to be caused by the release of a chemical called histamine from the extra blood cells. Treatments for itching include antihistamines, aspirin, certain antidepressants known as selective serotonin reuptake inhibitors (SSRIs), and light therapy.^[7][18]

The high turnover of red blood cells can lead to elevated levels of uric acid in the body, which may cause painful conditions such as gout (swelling and pain in joints, often the big toe) and kidney stones. Medications like allopurinol can help lower uric acid levels and prevent these complications.^[2][18]

An enlarged spleen, called splenomegaly, is another common issue. The spleen works hard to filter the excess blood cells, which causes it to swell. This can lead to a feeling of fullness or discomfort in the upper left part of the abdomen. Medications like ruxolitinib can help reduce spleen size.^[2]

Duration and Monitoring of Therapy

Treatment for polycythaemia vera is lifelong. Because the condition is chronic and has no cure, people need regular medical appointments to monitor their blood counts, adjust medications, and watch for complications. Blood tests are typically done every few months, and the frequency of phlebotomy depends on how well the disease is controlled. Over time, some people’s treatment plans may need to change based on how the disease evolves and how their body responds to therapies.^[5]

Treatment in Clinical Trials: The Future of Polycythaemia Vera Care

What Are Clinical Trials?

Clinical trials are research studies that test new treatments to see if they are safe and effective before they become widely available. Trials are conducted in phases. Phase I trials focus on safety and determining the right dose of a new drug, usually involving a small number of participants. Phase II trials test whether the treatment actually works and continues to monitor safety, with a larger group of people. Phase III trials compare the new treatment to the current standard treatment to see if it is better, involves even more participants, and provides the strongest evidence for approval by regulatory agencies.^[14]

Participating in a clinical trial can give patients access to cutting-edge treatments before they are available to the general public. However, trials also involve careful monitoring, additional tests, and sometimes uncertainty about whether the new treatment will work.

Rusfertide: A Promising New Drug

One of the most exciting developments in polycythaemia vera treatment is a drug called rusfertide. This medication works in a completely different way from traditional treatments. Rusfertide is a hepcidin mimetic, meaning it imitates a natural hormone produced by the liver called hepcidin. Hepcidin controls how much iron is available in the body for making red blood cells. By mimicking hepcidin, rusfertide blocks the production of iron-rich red blood cells, effectively reducing the need for repeated phlebotomies.^[14]

The first major clinical trial of rusfertide, called REVIVE, involved 70 people with polycythaemia vera who required frequent blood draws to keep their red blood cell counts under control. The results were striking. Before the trial, participants needed an average of nine phlebotomies per year. After starting rusfertide, this dropped to less than one phlebotomy per year. For most participants, the need for phlebotomy was significantly reduced or completely eliminated.^[14]

This is a major breakthrough because repeated phlebotomies cause significant fatigue and brain fog, and the constant need for clinic visits affects people’s quality of life. Rusfertide offers what researchers call a “chemical phlebotomy”—a way to achieve the same goals without physically removing blood. The trial results were published in the New England Journal of Medicine, and the drug is currently undergoing further testing. However, rusfertide is not yet approved by regulatory agencies such as the U.S. Food and Drug Administration (FDA) and is only available to people participating in clinical trials.^[14]

Ongoing Research and Other Experimental Therapies

Beyond rusfertide, researchers are studying several other hepcidin mimetics and innovative approaches to managing polycythaemia vera. These drugs aim to suppress red blood cell formation more specifically and with fewer side effects than current medications. Clinical trials are being conducted in various countries, including the United States, Europe, and other regions, and researchers are actively recruiting participants.^[14]

Scientists are also exploring ways to target the underlying genetic mutation that causes polycythaemia vera. Nearly all people with the condition have a mutation in the JAK2 gene, which leads to the overproduction of blood cells. While ruxolitinib already targets this pathway, researchers are working on even more precise and effective JAK2 inhibitors, as well as other molecules that might stop the disease at its root.^[3][5]

In addition to drug-based treatments, some research is looking at lifestyle interventions, dietary changes, and complementary approaches that might help manage symptoms and improve overall wellbeing. However, these are still in early stages and are not yet part of standard care.

Most Common Treatment Methods

• Phlebotomy (Blood Withdrawals)
  • The most common treatment, involving regular removal of blood to reduce red blood cell count and blood thickness.
  • Typically removes about one pint of blood per session, similar to blood donation.
  • Frequency varies from weekly at first to every few months once blood counts stabilize.
• Hydroxyurea
  • A chemotherapy drug in pill form that reduces bone marrow activity and lowers production of red blood cells, white blood cells, and platelets.
  • Used when phlebotomy alone is not sufficient or when other blood cell counts are elevated.
  • Requires regular blood tests to monitor effectiveness and side effects.
• Ruxolitinib (Jakafi)
  • A JAK2 inhibitor that blocks the abnormal protein causing overproduction of blood cells.
  • Can reduce the need for phlebotomy and shrink an enlarged spleen.
  • Prescribed when hydroxyurea does not work or causes intolerable side effects.
• Interferon
  • Given as an injection to lower blood counts and control disease activity.
  • Particularly useful in younger patients or during pregnancy when other treatments may not be suitable.
  • Can also help with symptoms like itching and weight loss.
• Low-Dose Aspirin
  • Helps prevent blood clots by reducing platelet stickiness.
  • Taken daily by many patients to lower the risk of heart attack, stroke, and other clot-related complications.
  • Not suitable for everyone due to increased bleeding risk.
• Rusfertide (Investigational)
  • A hepcidin mimetic currently being tested in clinical trials.
  • Blocks iron availability, reducing red blood cell production without the need for frequent phlebotomies.
  • In trials, reduced phlebotomy needs from nine per year to less than one per year.