ASH Clinical News September 2015 | Page 72

PAID ADVERTISEMENT Polycythemia Vera: Are Some Patients at Increased Risk? For some patients whose hematocrit levels remain elevated, and for those who continue to experience clinical signs and symptoms such as fatigue, pruritus, night sweats or splenomegaly, PV remains uncontrolled. Overview Thrombotic and hemorrhagic complications are among the leading causes of morbidity and mortality associated with PV.14 Cancer and What Is Polycythemia Vera? Polycythemia vera (PV) is a myeloproliferative neoplasm (MPN) cardiovascular mortality are the frequent causes of deaths in PV.6,15 characterized by an overproduction of When assessing risks for morbidity normal red blood cells, white blood cells and mortality in patients, consider and platelets that leads to an increased risk the following3,14,16: The rate of death of thrombosis.1-4 Erythrocytosis (elevated • Elevated hematocrit levels due to cardiovascular • History of thrombosis red blood cell mass) is the most prominent clinical manifestation of PV, distinguishing it events or major thrombosis • Advanced age (≥60 years) 5 • Leukocytosis from other MPNs. was four times higher • Cardiovascular risk factors such as high cholesterol levels, PV may occur at any age but often presents in patients with elevated hypertension, diabetes, obesity later in life, with a median age at diagnosis of 6,7 and smoking 60 years. Approximately 100,000 patients hematocrit levels of 45% 8 in the United States are living with PV. to 50% compared with According to data from a large, randomized, controlled clinical trial, Clinical Presentation of PV those who maintained the rate of death due to cardiovascular Contributing to Its Diagnosis a hematocrit target events or major thrombosis was Janus kinases (JAKs) mediate cytokine 9,1 0 four times higher in patients with signaling and growth factors. An 2 of <45%. elevated hematocrit levels of 45% important genetic discovery about a point to 50% compared with those who mutation in the Janus kinase 2 (JAK2) gene 11 maintained a hematocrit target of has enhanced the understanding of PV. <45%2 (Figure 1). The specific JAK2V617F mutation is detected in >95% of patients with PV.5 Although the JAK2V617F mutation is the key driver of PV, an understanding of the clinical presentation of PV will help to facilitate a more accurate diagnosis. PV PV is an elusive disease that may not be recognized for years. Diagnosis most frequently occurs by chance following a routine examination.12 Diagnosis may also occur after a thrombotic event or as a result of disease-related symptoms.12 The following important signs and symptoms warrant a prompt evaluation and suggest PV 6,7: • Elevated hemoglobin or hematocrit levels • Thrombotic events • Splenomegaly (with or without thrombocytosis and/or leukocytosis) Clinical Considerations in Managing PV Prognosis and Risk Factors In a large population-based study in more than 4,000 patients with PV, life expectancy was 36% lower than that of the general population.13 CI = confidence interval; Hct = hematocrit. Figure 1. Kaplan-Meier curve for total cardiovascular events. From The New England Journal of Medicine. Marchioli R, Finazzi, G, Specchia G, et al. Cardiovascular events and intensity of treatment in polycythemia vera. N Engl J Med. 2013;368(1):22-33. Copyright ©2013 Massachusetts Medical Society. Reprinted with permission from Massachusetts Medical Society. Thrombosis, Splenomegaly and Other Diseaserelated Symptoms In PV, a wide spectrum of thrombotic manifestations exists that may occur before the disease is diagnosed.14 Palpable splenomegaly is an important physical finding because increased spleen size is present in 30% to 40% of patients with PV.12 Additional signs and symptoms of PV, which may contribute to a substantial quality-oflife burden in patients with PV, include17: • Fatigue • Pruritus • Night sweats