Polycythemia vera (PV)

Blood cells are made in the bone marrow, the soft tissue inside bones. In polycythemia vera, the marrow makes too many red blood cells, and it may make too many white cells and platelets as well. The extra cells make the blood thicker, which raises the chance of blood clots.

PV is one of the myeloproliferative neoplasms (MPNs), a family of slow-growing blood cancers that also includes essential thrombocythemia and myelofibrosis. Many people live with PV for many years. It is a long-term condition that needs regular care rather than one short course of treatment.

PV is caused by a gene change that happens in a blood-forming stem cell during a person’s life. Almost everyone with PV has a change in the JAK2 gene. The change leaves a growth signal switched on, so the marrow keeps making blood cells the body does not need.

This gene change is not inherited from a parent, and it is not passed on to children. In rare families, several relatives have PV or another MPN; they seem to inherit a higher chance of getting it, not the disease itself. PV is not an infection and cannot be caught from anyone.

More than half of people with PV also have changes in other genes, such as TET2 or ASXL1. A few of these, including changes in SRSF2, IDH2, RUNX1 or U2AF1, are linked to a poorer outlook.

Some people have no symptoms and learn they have PV from a routine blood test. Others have headaches, dizziness, vision changes, a red face, or itching all over, often after a warm bath or shower. An enlarged spleen can cause pressure or fullness under the ribs on the left side.

The biggest danger is a blood clot. A clot can cause a stroke, a heart attack, or a clot in a deep vein or the lungs. The risk is higher in people over 60 and in people who have already had a clot.

Over many years, PV can change into myelofibrosis, in which scar-like fibers build up in the marrow, or into acute myeloid leukemia. This happens to a minority of people. Older age and a high white-cell count are among the things linked to a higher chance.

Living with PV usually means regular blood tests and clinic visits for years, and repeated phlebotomy for many people. Frequent phlebotomy can leave the body short of iron, which can cause symptoms such as a sore tongue, cracks at the corners of the mouth or muscle weakness. Itching can go on even when blood counts are under control.

Because clots are the main risk, care teams also pay attention to other things that affect the heart and blood vessels, such as blood pressure, cholesterol, diabetes and smoking. Surgery and pregnancy need special planning with the care team.

The team also watches for signs that PV may be changing, such as a growing spleen, anemia or no longer needing phlebotomy, or new symptoms common in myelofibrosis, like fever, drenching night sweats or weight loss. If that happens, a bone marrow biopsy can show whether it has become myelofibrosis.

PV itself is not treated with a stem cell transplant. European transplant experts (EBMT) state that PV is not a reason for a donor transplant unless it has turned into myelofibrosis, or into MDS or leukemia. They also do not recommend a transplant using a person’s own cells for MPNs.

If PV does progress, a donor (allogeneic) transplant may be considered for people with higher-risk myelofibrosis who are fit enough, because it is the only treatment that may cure it. In a study by EBMT, the European transplant society, of 2,809 people who had a first donor transplant for myelofibrosis in 2015–2021, about 6 in 10 received cells from an unrelated volunteer, either fully or partly matched.

Most people with PV will never need a donor. For the few whose disease becomes higher-risk myelofibrosis or leukemia, a registry volunteer may make a transplant possible. No one can promise a match for a particular person.