Increased red cell mass has been variably termed either erythrocytosis or polycythemia; no clear consensus for either term has been achieved. Some interpret meaning of polycythemia to imply that several lineages are increased (ie, erythrocytosis, neutrophilia, and thrombocytosis); the only form of polycythemia is polycythemia vera. Others, such as the late Allan Erslev, the author of earlier editions of Williams Hematology, argued that the proper meaning of polycythemia is too many cells in blood. Hence, one cannot have 6 × 109/L of leukocytes or platelets, but more than 6 × 109/L is seen in many conditions described here. Because the acceptance of first definition is increasing, this chapter reserves the term polycythemia only for polycythemia vera. This may lead to initial difficulties when reviewing the literature as the entities of Chuvash polycythemia, now Chuvash erythrocytosis. Similarly, the autosomal dominant erythrocytosis stemming from the germ line gain-of-function mutations of erythropoietin receptor is generally known as primary familial and congenital polycythemia but will be referred here as erythrocytosis.
Primary polycythemias/erythrocytoses are caused by acquired or inherited mutations causing functional changes within hematopoietic stem cells or erythroid progenitors leading to an accumulation of red cells. The most common primary erythrocytosis, polycythemia vera, which is a clonal disorder, is discussed in Chap. 83. The other primary erythrocytosis that is inherited from mutations in the erythropoietin receptor is discussed herein. In contrast, secondary erythrocytoses are caused by either an appropriate or inappropriate increase in the red cell mass, most often as a result of augmented levels of erythropoietin; these erythrocytoses can also be either acquired or hereditary. Some congenital disorders of hypoxia sensing share features of both primary and secondary erythrocytoses, and these are also discussed here. Although the clinical presentations of primary and secondary erythrocytoses may be similar, distinguishing among them is important for accurate diagnoses and proper management.
For example, secondary erythrocyrosis states that represent an appropriate physiological compensation to tissue hypoxia should not be treated by phlebotomies. An occasional patient may experience hyperviscosity symptoms and may benefit from isovolemic reduction of hematocrit. Inappropriate erythrocytoses are caused by erythropoietin-secreting tumors; self-administration of erythropoiesis-stimulating agents, including, inherited disorders of hypoxia sensing; or, rarely, some endocrine disorders (described in Chap. 39). Correction of hypoxia, discontinuation of erythropoiesis-stimulating agents, or resection of erythropoietin-secreting tumors typically corrects the associated erythrocytosis.
Acronyms and Abbreviations
BFU-E, burst forming unit–erythroid; 2,3-BPG, 2,3-bisphosphoglycerate; CFU-E, colony forming unit–erythroid; COPD, chronic obstructive pulmonary disease; EGLN1, a gene encoding for PHD2; EPAS1, a gene encoding for HIF2 a; EPOR, erythropoietin receptor (protein); FIH-1, HCP, hematopoietic phosphatase; HIF, hypoxia inducible factor; HUMARA, human androgen-receptor gene; JAK, Janus type tyrosine kinase; NF KbOSA, obstructive sleep apnea; PFCP, Primary familial and congenital erythrocytosis; PAI-1, plasminogen activator inhibitor; PHD2, proline hydroxylase 2; STAT, Signal transducer and activator of transcription; VEGF, vascular endothelial growth factor; VHL, von Hippel Lindau syndrome.