Polycythemia vera (PV) is a myeloproliferative disorder with excessive proliferation of red cells, megakaryocytes, and myelocytes. It is usually an insidious disease with gradual onset and can be associated with prolonged survival if the cytosis is controlled. Splenomegaly is common and is frequently one of the presenting features. The clini-cal course of PV can be quite varied. With uncontrolled proliferation of red cells and platelets, an increase in whole blood viscosity can occur, leading to impairment of blood flow to critical organs. Central nervous system and cardiovascular symptoms, including confusion, angina, and claudication, can occur as a result of insufficient oxygen delivery. Thrombotic complications are a significant cause of morbidity and mortality, with strokes, myocardial infarctions, arterial occlusions, and thromboembolic complications being common. There is also an increased risk of hemorrhage.

The long-term course of PV can include distinct phases. Initially, an asymptomatic phase may be associated with only mild elevation of the red cell mass and mild splenomegaly; this gives way to an erythrocytic phase associated with pancytosis, with complications such as thrombosis and hemorrhage. An inactive phase may ensue in which no therapy is required to control the proliferative cells, and eventually a postpolycythemic myeloid metaplasia phase can develop with evidence of marrow fibrosis and extramedullary hematopoiesis. A significant percentage of patients with PV will culminate in acute nonlymphocytic leukemia. The ongoing management of patients during the erythrocytic phase affects the risks of developing this devastating outcome.

Although PV increases in incidence with advancing age, there is a wide range of ages, including some childhood cases. There is no known cause, and surprisingly there is no link to radiation exposure. In mice, the friend erythroleukemia virus causes a similar disease, but no viral infection has been found associated with PV in humans.

The diagnosis of PV rests on a combination of clinical and laboratory findings. The polycythemia study group established the diagnostic criteria shown in

Table 38.1. The most important step is to confirm that the red cell mass is actually increased using chromium-51 red cell labeling and a plasma volume study. In many patients with apparently elevated hematocrit, the red cell mass is normal and the plasma volume is below normal or reduced, giving a spuriously increased hematocrit without true polycythemia; this effect can be seen in patients on a diuretic or patients known to have spurious erythrocytosis.

Once the red cell mass is confirmed to be elevated, other primary causes must be evaluated. Hypoxia either from lung disease or as a result of an abnormal hemoglobin variant, as well as erythropoietin-producing renal tumors, needs to be evaluated. The leukocyte alkaline phosphatase score is frequently elevated as opposed to the situation in CML.

Treatment for the patient with PV needs to be individualized. Phlebotomy can reduce the hematocrit quickly. However, in elderly patients, one has to be careful to avoid inducing significant hemodynamic changes that could further compromise the circulation. Very few patients are managed with phlebotomy alone.

The PV study group evaluated three common treatments: phlebotomy, P, and chlorambucil. None of these treatments was without shortcomings. Patients who were managed with phlebotomy alone had a significantly increased risk of thrombotic complications, which appears to be independent of the level of hematocrit or platelet count. Patients treated with P or chlorambucil had a markedly increased risk of developing acute leukemia. Hydroxyurea has emerged as a primary option for many patients. It is well tolerated, and, although not devoid of mutagenic risks, it appears to have significantly less risk than alkylating therapy for the development of acute leukemia.

The goal of therapy should be to maintain the hematocrit in the range of 42% to 45%. There is a direct relationship between the level of hematocrit and the risk of vascular occlusive episodes. Other goals of therapy include control of the frequently associated pruritis with histamine antagonists. Elective surgical procedures should be delayed until counts have been controlled for at least 2 months to reduce the risk of hemorrhage or thrombosis. Aspirin and other antiplatelet agents have not been proven to reduce the risk of thrombotic events and may, in fact, increase the risk of hemorrhage and are not routinely recommended. The prognosis for patients with controlled PV is excellent as compared with the other hematologic malignancies. Long-term survival is common.

Future directions for patients with polycythemia vera include the use of interferon-alpha. In early studies, it appears to be active in reducing the red cell mass and platelet counts. Although side effects of interferon continue to limit its use in older patients, it can be useful in patients with extreme thrombocytosis.