Chapter 43: Polycythemia Vera

INTRODUCTION

• Polycythemia vera (PV) is a clonal disorder due to 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, granulocytic, and megakaryocytic cells. PV is one of the chronic myeloproliferative disorders (MPDs): essential thrombocythemia (ET), primary myelofibrosis (PMF), and chronic myelogenous leukemia (CML); these disorders are also called myeloproliferative neoplasms (MPN).

• Three myeloproliferative neoplasms (PV, ET, PMF) share a common molecular abnormality/marker, the JAK2 kinase V617F mutation.

ETIOLOGY AND PATHOGENESIS

• PV arises from the neoplastic transformation of a single hematopoietic multipotential cell, which provides both a selective growth and survival advantage that results in the cells produced in the clone suppressing and replacing normal polyclonal hematopoiesis.

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

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

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

• Familial incidence of PV and/or other MPDs, occurs in about 5 percent 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: headache, plethora, pruritus, thrombosis (esp. Budd-Chiari syndrome), erythromelalgia, and gastrointestinal bleeding. Many patients diagnosed because of elevated hemoglobin and/or platelets on routine medical examination. Other cases may be uncovered during investigation for blood loss, iron-deficiency anemia (sometimes as a result of prior bleeding), or thrombosis. Symptoms are reported by at least 30 percent 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 significant clinical manifestations of PV; they may occur prior to diagnosis of the disease.

• Thrombotic episodes are the most common and the most important complications, occurring in about one-third of the patients; these may be fatal, and include stroke, myocardial infarction, deep venous thrombosis, hepatic vein thrombosis, and pulmonary embolism.

• Bleeding and bruising are common complications of PV, occurring in about one-quarter of the patients in some series (generally when platelet count over 1000 × 10⁹/L). Whereas such episodes (such as gingival bleeding, nose bleeding, or easy bruising) are usually minor, serious gastrointestinal bleeding (which may mask polycythemia) and other hemorrhagic complications with a fatal outcome also can occur.

• Patients with uncontrolled PV undergoing surgery have a high risk of bleeding and/or thrombosis. Phlebotomy should be used to decrease hematocrit prior to surgery to lessen risk.

LABORATORY FEATURES

• The most consistent is a mutation in exon 14 of JAK2 kinase, present in >95 percent of PV ...