Polycythemia Vera Risk Stratification

Harry Erba, MD, PhD:The most important complication to be considering in patients with polycythemia vera is the risk of thromboembolic disease. The two most important risk stratifiers in this disease are age, arbitrarily defined as over 60, and a prior history of a thromboembolic event. Those two will classify patients as high-risk. However, it should be considered that patients may have other risk factors for thromboembolic events, and these should also be considered when determining the treatment for these patients. So, in a patient who is 58 years old and has not had a prior thromboembolic event, but has poorly controlled diabetes mellitus, hypertension, is a current tobacco user, and has a strong family history of thromboembolic disease—these are all factors that the physician should weigh in deciding when to intervene in the disease.

Another factor that has been associated with the risk of thrombosis is leukocytosis, which I actually do think is an important one to consider. I think pathophysiologically it makes sense. If the white blood cell count is elevated, that can lead to more sluggish blood flow in the microcirculatory because of adhesion of white cells to the endothelial surface. It’s interesting to me that in another disease that is characterized by vaso-occlusive events, sickle cell anemia, leukocytosis has also been associated with an increased risk of painful crises.

The most important complications to consider in polycythemia vera are the thromboembolic events, and these can be major thromboembolic events, such as myocardial infarction, cerebrovascular accidents, pulmonary emboli, or unusual thromboembolic events, such as Budd-Chiari or portal vein thrombosis, mesenteric vein thrombosis, for example. But there could also be microcirculatory events that complicate the disease, such as erythromelalgia, that is often diagnostically and therapeutically evaluated by taking a dose of aspirin.

Patients may have migraine headaches, dizziness, auras with their migraine headaches, or tinnitus. These are all signs of microcirculatory compromise due to the disease. The risk factors that have been identified in polycythemia vera—age, prior thromboembolic events, and leukocytosis—are all events that will compromise survival. And the major risk of mortality in this disease has been linked to thromboembolic disease.

So, in this disease, we are looking at those risk factors that increase the risk of clotting. For example, we are not looking at risk factors that had been shown to increase the risk of post-PV myelofibrosis or transformation to acute leukemia. In contrast to another myeloproliferative neoplasm, such as chronic myeloid leukemia, where the risk factors had been linked with mortality associated with a higher risk of progression, the risk factors in PV are related to the major complication of the disease, thromboembolic events.

A Patient with Disease Progression on Hydroxyurea

Case 1: