Chapter 70 - The Polycythemias

Abstract

Under normal conditions, the red blood cell (RBC) mass in humans is tightly controlled and remains relatively constant in a given individual. The numbers of senescent RBCs lost daily are replaced by newly formed ones by a carefully controlled network of growth factors, progenitor and precursor cells. Erythropoiesis can be augmented by a variety of stimuli that increase the delivery of oxygen to tissues. This delicate balance can be disturbed by various pathologic conditions and can result in either reduced numbers of RBCs (anemia) or excessive numbers of RBCs (polycythemia). Hematocrit values over 49% in males and 48% in females are abnormal and require further evaluation to determine if the patient has an absolute increase in their RBC mass and if investigation of its cause should be pursued. The RBC mass is increased if it is greater than 125% above that expected for sex and body mass. The measurement of the RBC mass is a diagnostic study that is now available at a dwindling number of tertiary care centers, making other diagnostic studies pivotal in evaluating patients with elevated hematocrit levels. Polycythemic states can be due to a variety of disorders that can be attributed to several pathophysiologic mechanisms. Determination of the etiology of an individual's polycythemia is a critical step in defining the patient’s appropriate prognosis and treatment plan. Primary polycythemias are the result of innate abnormalities involving hematopoietic progenitors and stem cells that lead to constitutive overproduction of RBCs, accompanied by low erythropoietin (EPO) levels. By contrast, secondary polycythemias are the consequence of a number of conditions that lead to increased EPO production, which acts on normal progenitors to overproduce RBCs. In a small number of patients, the cause of erythrocytosis cannot be determined; these patients are classified as having idiopathic erythrocytosis.