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  • Erythrocytosis, also referred to as polycythemia, is characterized by an increased red cell mass. There is no consensus on terminology as it relates to the choice of erythrocytosis or polycythemia (ie, primary familial and congenital polycythemia but postrenal transplantation erythrocytosis). Herein, the term polycythemia will only be used for polycythemia vera, an acquired clonal disorder caused by somatic mutations (Chap. 42), and polyclonal erythrocytosis will be used for all other states discussed in this chapter.

  • An erythrocytosis can be primary or secondary and can be inherited or acquired.

  • Classification of polycythemic disorders appears in Table 2–2 in Chap. 2.

  • A primary polycythemia/erythrocytosis is caused by somatic or germline mutations within hematopoietic stem cells or erythroid progenitors that result in an augmented response to erythropoietin (EPO). This response is not a compensation for hypoxia and thus is inappropriate for tissue needs.

  • A secondary erythrocytosis is caused by either an appropriate (compensatory) or inappropriate increase in the red cell mass and, in most instances, results from an augmented level of EPO.


  • The most common primary polycythemia, polycythemia vera, is an acquired clonal stem or multipotential hematopoietic progenitor cell disorder discussed in Chap. 42. It is a myeloproliferative neoplasm. The root “polycyt” reflects the usual presence of multilineage exaggerated production of cells (eg, red cells, neutrophils, and/or platelets in most cases).

Primary Familial and Congenital Erythrocytosis

  • This disorder is autosomal dominant, with normal leukocyte and platelet counts.

  • Affected persons are often misdiagnosed as having polycythemia vera.

  • Low plasma EPO level is a constant feature (Figure 27–1).

  • Erythroid progenitors in in vitro cultures are hypersensitive to EPO, but unlike the erythroid progenitors in polycythemia vera, they do not grow in the absence of EPO.

  • This condition is caused by gain-of-function mutations of the EPO receptor, mostly by deletions of the negative regulatory cytoplasmic domain.

  • Affected individuals may have an increased risk of cardiovascular complications, regardless of control of elevated hematocrit by phlebotomies.


Diagnostic algorithm for erythrocytosis based on erythropoietin (EPO) level. 2,3-BPG, 2,3-bisphosphoglycerate; BFU-E, burst-forming unit–erythroid; EPOR, erythropoietin receptor gene; HIF2α, hypoxia-inducible factor 2α; encoded by EPAS1 gene; PHD2, prolyl hydroxylase 2, encoded by EGLN1 gene; VHL, von Hippel-Lindau gene; TEMPI syndrome, telangiectasias, erythrocytosis with elevated EPO levels, monoclonal gammopathy, perinephric fluid accumulation, and intrapulmonary shunting.


  • This group of disorders is marked by increased red cell mass (absolute erythrocytosis) because of stimulation of red cell production mostly by increased EPO production. The erythrocytosis is considered:

    Appropriate if there is tissue hypoxia and the increased red cell mass (increased blood hemoglobin concentration) is compensatory and minimizes the hypoxia.

    Inappropriate if tissue hypoxia is absent and the erythrocytosis serves no useful purpose.

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