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Myeloproliferative Neoplasms Case Studies

Polycythemia Vera Disease Burden

Published Online:Oct 12, 2016
Srdan Verstovsek, MD, provides information on the diagnosis and treatment of patients with polycythemia vera.

Srdan Verstovsek, MD, provides information on the diagnosis and treatment of patients with polycythemia vera: Case 1



Srdan Verstovsek, MD: Polycythemia vera is one of the myeloproliferative neoplasms. Myeloproliferative neoplasms are chronic diseases of the bone marrow where cells grow without control, but they do not change the shape. They just grow without control and overwhelm the bone marrow and overwhelm the blood. Polycythemia vera is one type of the spectrum of the diseases where primarily red blood cells grow without control, but white blood cells and platelets can be high as well. So, there are too many cells in blood. It can cause a lot of symptoms, primarily due to obstruction of the blood flow. The blood flow is sluggish when you have too many blood cells, so people can have a number of problems like blurred vision, headaches, itching, night sweating, tingling in the fingers and toes, poor memory, fatigue, and weakness. There are many problems, and, of course, there is increased risk of blood clotting. The blood can stop flowing through the blood vessel and cause a lot of symptoms through the cessation of the blood through the blood vessels.

It’s a chronic disease, but it carries a lot of symptoms and the risk of morbidity related to the increased risk of thrombosis. We learn over time that polycythemia vera is driven by hyperactivity of the JAK/STAT pathway. This is a pathway inside the cells in the bone marrow that in a normal person is involved in the blood making. But, in this disease, it is also an essential thrombocythemia and myelofibrosis to other types of myeloproliferative neoplasms. That’s a spectrum of these diseases. All are connected by an underlying biological problem of hyperactivity of the JAK/STAT pathway. This is usually active when we need to make blood, but in these conditions, it’s active because of different mutations that lead to its hyperactivity and the cells grow without control.

The JAK mutation is particularly a cause for this hyperactivity in polycythemia vera. The JAK2 V617F mutation is present in about 95% of patients with PV, and in a few other percentages, the mutation is in a different part of the JAK2 gene. It’s called JAK2 exon 12. There are other occasional other cases where we still don’t know where the mutation is that leads to JAK/STAT activation. But, we know for sure that the JAK/STAT pathway activation is an underlying problem.

Polycythemia vera can present in different ways. This is a disease where there are too many blood cells in the blood and that causes increase for blood clotting. So, one way of presenting is to have a blood clot, and 20% to 30% of patients, in fact, can be discovered to have a disease of the blood at the presentation with a blood clot. Others may present to local doctors with the symptoms related to the sluggish blood flow through their body. That would be itching after taking a hot shower, fogginess, blurred vision, headaches, tingling in the fingers and toes, fatigue, and weakness. Some even have an enlarged spleen, abdominal fullness, redness of the skin. These are a number of symptoms that can accompany polycythemia vera. And yet, another group of patients may just be discovered on a routine annual physical exam to have abnormalities in the blood count or on physical exam with enlarged spleen. That leads to a discovery of polycythemia vera without any symptoms or signs.

Regardless of a presentation, our goal is to decrease the risk of thrombosis. People live a long life, usually close to normal, but the risk of thrombosis is the problem. We do this by performing phlebotomy, which is a bloodletting, and give people aspirin. In many patients, we also institute what we call cytoreductive therapy, medications to decrease the blood cell count and decrease further risk of thrombosis. But, that does not always work. And, here, at MD Anderson in Houston, we see patients in consultations quite often.

There are two types of consultations, in general. One is to make sure the diagnosis is right. Indeed, there is no one single test that will diagnose PV. The JAK2 mutation is just one of the factors that needs to be present for a diagnosis to be made. There are definitely other factors, and sometimes it’s not clear-cut. The other problem is once you have a diagnosis and you treat the patients, they may not do well. So, we are a referral center where we provide new options. We have actually contributed to development of new options for patients with polycythemia vera that don’t do well with standard therapy. And, I would say I see about 30 to 50 patients with polycythemia vera a year here in Houston.

 

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