Chapter 41: Polycythemia Vera

INTRODUCTION

• Polycythemia vera (PV) is a clonal disorder arising from somatic mutations of a multipotential hematopoietic cell, in which blood cell production, notably erythropoiesis, is increased independent of cytokine regulation. This results in exaggerated proliferation and accumulation of erythrocytic, and often also granulocytic, and megakaryocytic cells. PV is one of the myeloproliferative neoplasms (MPN), along with essential thrombocythemia (ET), primary myelofibrosis (MF), and chronic myelogenous leukemia (CML).

• Three myeloproliferative neoplasms (PV, ET, MF) share a common molecular abnormality/marker, the JAK2 kinase V617F mutation. CML stands alone; it has a different molecular marker (bcr/abl, due to a reciprocal translocation between chromosome 9 and chromosome 22, t(9;22)(q34;q11)).

ETIOLOGY AND PATHOGENESIS

• PV arises from a neoplastic transformation of a single hematopoietic multipotential cell, which then produces a clone that suppresses and replaces normal polyclonal hematopoiesis, providing both selective growth and survival advantages to cells produced in the clone.

• The JAK2 kinase V617F mutation directly activates erythropoietin (EPO) receptor signaling.

• In vitro erythroid colonies develop in the absence of added EPO and are characteristic for PV.

• Karyotypic abnormalities are not specific; they develop later in the disease and may portend transformation into myelofibrosis or myelogenous leukemia.

• Familial incidence of PV and/or other MPDs occurs in about 5% to 7% of patients.

• Incidence ranges from 1 to 2.5 per 100,000 reported in different countries.

CLINICAL FEATURES

• PV usually has an insidious onset, most commonly during the sixth decade of life, although may occur at any age, including childhood.

• Presenting symptoms and signs may include headache, plethora, aquagenic pruritus, thrombosis (especially Budd-Chiari syndrome), erythromelalgia, and gout. Many patients are diagnosed because of elevated hemoglobin and/or platelets on routine medical examination. Other cases may be uncovered during investigation for blood loss, iron deficiency, erythromelalgia, or thrombosis. Symptoms are reported by at least 30% of patients with polycythemia at the time of diagnosis.

• Neurologic complaints include vertigo, diplopia, scotomata, and transient ischemic events.

• Associated disorders include peptic ulcer disease and gout.

• Thrombotic and hemorrhagic events are the most common and most important complications of PV. They may occur prior to diagnosis of the disease in about one-third of patients and may be fatal. These events include stroke, myocardial infarction, deep venous thrombosis, splanchnic vein thrombosis (mostly Bud Chiari syndrome), mesenteric vein thrombosis and portal vein thrombosis, and pulmonary embolism.

• Bleeding and bruising are common complications of PV, occurring in about 25% of patients in some series (generally when platelet count is > 1000 × 10⁹/L). Although such episodes (such as gingival bleeding, epistaxis, or easy bruising) are usually minor, serious gastrointestinal bleeding (which may mask polycythemia) and other hemorrhagic complications with fatal outcomes also can occur.

• Patients with uncontrolled PV undergoing surgery have a high risk of bleeding and/or thrombosis. Phlebotomy is recommended by many to decrease hematocrit prior to surgery to lessen risk.

LABORATORY FEATURES