Polycythemia Vera (PV)

Polycythemia vera (PV) is a myeloproliferative neoplasm (MPN) in which a mutation in blood stem cells lead to an excessive production of red blood cells. In addition to this, also the number of white blood cells and blood platelets are often increased in PV patients. Too many red blood cells can make the blood thicker, which makes it more difficult for the blood to flow around the body. This reduced blood flow increases the risk for thrombosis and other heart conditions, such as a heart attack, or a stroke. In some patients with PV, also the spleen produces an excessive amount of blood cells, which can make the spleen become enlarged.

In general, PV progresses very slowly, and the disease often remains undiagnosed until after the age of 60. PV is more common in men than in women and in about 95% of patients, a mutation can be found in the JAK2 gene. This gene encodes a protein that controls the production of blood cell precursors and as a result of the mutation, these cells continue to produce an excess amount of (mainly red) blood cells.

While PV generally progresses slowly, the overproduction of red blood cells increases the risk for blood clots. Furthermore, the high red blood cell turnover in PV patients leads to high levels of uric acid in the body. In turn, these high uric acid levels can lead to several secondary conditions, including kidney stones (when uric acid builds up in your kidneys) or gout (when uric acid builds up in your joints). In addition, an excessive amount of red blood cells also increases the production of stomach acid, which may lead to the development of stomach ulcers.

In rare cases, PV may progress to other more aggressive blood disorders, including myelofibrosis, myelodysplastic syndrome (MDS), or (rarely) acute myeloid leukemia (AML).

The diagnosis of PV can be made on a blood sample. The presence of a JAK2 mutation in combination with a low level of erythropoietin confirms the diagnosis. If no JAK2 mutation is found, a bone marrow biopsy can be performed. In case of PV, this bone marrow sample will show large and abnormal megakaryocytes. In addition to this, patients may undergo an ultrasound of the abdomen to assess the size of their spleen.

While PV is a chronic, incurable disease, it can usually be managed effectively. The goal of therapy is to reduce the risk of thrombosis and to alleviate the PV symptoms by lowering the number of extra blood cells.

In early disease stages, PV is treated conservatively, with therapies including a phlebotomy to reduce the blood volume and low-dose aspirin to reduce the risk of blood clotting. In addition, cardiovascular risk factors (e.g. smoking, hypertension, high cholesterol) should be identified and controlled to further reduce the risk of thrombosis. In patients with a high risk for blood clots, such as people above the age of 60 years or people who suffered a thrombosis in the past, treatment will be initiated.

In patients with a higher risk for blood clots, treatment will be initiated to reduce the blood cell levels (i.e., cytoreduction). The drugs that are used to accomplish this cytoreduction include chemotherapy with hydroxycarbamide, targeted therapy with the JAK2 inhibitor ruxolitinib, and interferon alfa (not available in Belgium for this indication). In case of an evolution to AML, physicians may consider a stem cell transplantation. Finally, participation in clinical trials may provide access to alternative treatment options to patients.