PV is generally an indolent disorder, the clinical course of which is measured in decades, and its management should reflect its tempo. Thrombosis due to erythrocytosis is the most significant complication, and maintenance of the hemoglobin level at ≤140 g/L (14 g/dL; hematocrit <45%) in men and ≤120 g/L (12 g/dL; hematocrit <42%) in women is mandatory to avoid thrombotic complications. Phlebotomy serves initially to reduce hyperviscosity by bringing the red cell mass into the normal range. Periodic phlebotomies thereafter serve to maintain the red cell mass within the normal range and to induce a state of iron deficiency that prevents an accelerated reexpansion of the red cell mass. In most PV patients, once an iron-deficient state is achieved, phlebotomy is usually only required at 3-month intervals. Neither phlebotomy nor iron deficiency increases the platelet count relative to the effect of the disease itself, and thrombocytosis is not correlated with thrombosis in PV, in contrast to the strong correlation between erythrocytosis and thrombosis in this disease. The use of salicylates as a tonic against thrombosis in PV patients is not only potentially harmful if the red cell mass is not controlled by phlebotomy, but also an unproven remedy. Anticoagulants are only indicated when a thrombosis has occurred and can be difficult to monitor owing to the artifactual imbalance between the test tube anticoagulant and plasma that occurs when blood from these patients is assayed for prothrombin or partial thromboplastin activity if the red cell mass is substantially elevated. Asymptomatic hyperuricemia (<10 mg%) requires no therapy, but allopurinol should be administered to avoid further elevation of the uric acid when chemotherapy is employed to reduce splenomegaly or leukocytosis or to treat pruritus. Generalized pruritus intractable to antihistamines or antidepressants such as doxepin can be a major problem in PV; interferon α (IFN-α), psoralens with ultraviolet light in the A range (PUVA) therapy, and hydroxyurea are other methods of palliation. Asymptomatic thrombocytosis requires no therapy unless the platelet count is sufficiently high to cause an acquired form of von Willebrand's disease due to adsorption and proteolysis of high-molecular-weight von Willebrand factor (vWF) multimers by the expanded platelet mass. Symptomatic splenomegaly can be treated with IFN-α, although the drug can be associated with significant side effects when used chronically. Pegylated IFN-α produces complete remissions in PV patients, and its role in this disorder may be expanding. Anagrelide, a phosphodiesterase inhibitor, can reduce the platelet count and, if tolerated, is preferable to hydroxyurea because it lacks marrow toxicity and actually is protective against venous thrombosis. A reduction in platelet number may be necessary for the treatment of erythromelalgia or ocular migraine if salicylates are not effective or if the platelet count is sufficiently high to cause a hemorrhagic diathesis but only to the degree that symptoms are alleviated. Alkylating agents and radioactive sodium phosphate (32P) are leukemogenic in PV, and their use should be avoided. If a cytotoxic agent must be used, hydroxyurea is preferred, but this drug does not prevent either thrombosis or myelofibrosis in this disorder, is itself leukemogenic, and should only be used for as short a time as possible. In some patients, massive splenomegaly unresponsive to reduction by therapy and associated with intractable weight loss will require splenectomy. In some patients with end-stage disease, pulmonary hypertension may develop due to fibrosis and extramedullary hematopoiesis. Allogeneic bone marrow transplantation may be curative in young patients. Several JAK2 inhibitors are undergoing clinical trial; to date, these agents have been demonstrated to alleviate constitutional symptoms and to rapidly reduce spleen size without significant effects on blood counts or the JAK2 V617F neutrophilallele burden, suggesting that they may at least have an important palliative role.
Most patients with PV can live long lives without functional impairment when their red cell mass is effectively managed with phlebotomy alone. Chemotherapy is never indicated to control the red cell mass unless venous access is inadequate.