We like to frame our discussions with patients with PV to ensure that they understand the benefits of tighter blood count control and of bringing the hematocrit level to below 45%. Studies have shown that this level of control is associated with lower rates of thrombosis and myocardial infarction. I also inform patients that it is possible to be symptomatic despite having a lower hematocrit level; in fact, they may experience some symptoms (eg, headache, erythromelalgia) when their hematocrit reaches 42%. We offer these individuals phlebotomy. With respect to their white blood cell count, we will often discuss leukocytosis as another risk factor in some patients, in addition to their hematocrit level. Although thrombocytosis is uncommon in patients with PV, it is, however, a risk factor for thrombotic complications. We try to get the patient’s platelet count to as close to normal as possible, but the optimal platelet count in those with PV is unknown; I am not aware of any precise correlation between the actual platelet count and the risk of thrombosis. In fact, when platelet counts get too high (ie, >1 million), the risk of bleeding can actually increase. Low-dose aspirin is recommended in all patients with PV, provided that there are no major contraindications; however, in the presence of aspirin-resistant symptoms, symptom relief may be a better therapeutic goal than any particular platelet count.

Leukocytosis is a major risk factor for thrombosis in patients with PV. Like the platelet count, we try to get the leukocyte count to as close to normal as possible, but, again, the ideal count is unknown. Phlebotomy and cytoreductive therapy with hydroxyurea can lower both hematocrit levels and leukocyte counts, but some patients are resistant to or are intolerant of hydroxyurea. Higher doses of hydroxyurea are associated with adverse events, including leg ulcers and mucositis. In Europe, interferon has demonstrated therapeutic responses in patients with PV that are similar to those seen with hydroxyurea; a small subset of patients achieve complete remission with interferon and are able to avoid disease recurrence—even after discontinuing the treatment. But the major limitation of interferon is toxicity, with more than half of patients discontinuing treatment. Pegylated interferon may have fewer side effects. Ruxolitinib is still a valuable option for second-line cytoreductive therapy in PV, particularly for those who have constitutional symptoms or pruritus, as ruxolitinib is well tolerated and enables patients to achieve the best control of this set of symptoms.