Skip to Main Content

Polycythemia is characterized by an increased red cell volume. Primary polycythemias are caused by acquired or inherited mutations causing changes within hematopoietic stem cells or erythroid progenitors, leading to an accumulation of red cells. The most common primary polycythemia, polycythemia rubra vera, which is a clonal disorder, is discussed in Chap. 86, but other inherited polycythemias, such as mutations in the von Hippel-Lindau (VHL) gene or in the erythropoietin receptor (EPOR) gene are discussed herein. In contrast, secondary polycythemias are caused by either an appropriate or inappropriate increase in the red cell mass as a result of augmented levels of erythropoietin; these polycythemias can also be either acquired or hereditary. Although the clinical presentations of primary and secondary polycythemias may be quite similar, distinguishing among them is important for accurate diagnoses and proper management.

For example, many secondary polycythemic states represent an appropriate physiologic compensation to tissue hypoxia, and it is unwise to treat these by phlebotomies. There is no solid evidence that either congenital or acquired primary or secondary polycythemias benefit from phlebotomies; however, an occasional patient may experience hyperviscosity symptoms and may benefit from isovolemic reduction of hematocrit. Enalapril controls post-renal transplantation erythrocytosis, and resection of erythropoietin-secreting tumors typically corrects the associated polycythemia.

Acronyms and Abbreviations

Acronyms and abbreviations used in this chapter include: AR, human androgen-receptor gene; 2,3-BPG, 2,3-bisphosphoglycerate; COPD, chronic obstructive pulmonary disease; EPOR, erythropoietin receptor (protein); EPOR, erythropoietin receptor (gene); HIF-1, hypoxia-inducible factor; JAK, Janus-type tyrosine kinase; PAI-1, plasminogen activator inhibitor; PFCP, primary familial and congenital polycythemia; PHD2, proline hydroxylase 2; STAT, signal transducer and activator of transcription; VEGF, vascular endothelial growth factor; VHL, von Hippel-Lindau syndrome.

The term polycythemia, denoting an increased amount of blood, has traditionally been applied to those conditions in which the mass of erythrocytes is increased. Erythrocytosis is an alternative term that has been applied to an increase in red cell mass. Although this usage has much to recommend it, no consensus about terminology has been reached. Many physicians use erythrocytosis interchangeably with polycythemia. In some instances, however, time-honored terms such as post-renal transplantation erythrocytosis will be used. A classification of the polycythemias is presented in Chap. 33 in Table 33–2.

Primary Polycythemias

Polycythemia vera (see Chap. 86) and primary familial and congenital polycythemia (PFCP) are primary polycythemic disorders with erythroid progenitors that are hypersensitive to erythropoietin.1–3 These are a result of somatic (polycythemia vera) or germ-line (PFCP) mutations that are intrinsic to erythropoietic progenitors and result in an augmented response to erythropoietin. Some congenital polycythemias, as best described in Chuvash polycythemia, have erythroid progenitors that are hypersensitive to erythropoietin but also may have normal or even increased erythropoietin levels despite the increased red cell volume.4,5 Thus, these rare, inherited polycythemias share features of both primary and secondary polycythemias.6

Secondary ...

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.