Chapter 27: Polyclonal Polycythemias (Primary and Secondary)

INTRODUCTION

• Polycythemia, also referred to as erythrocytosis, is characterized by an increased red cell mass. There is no consensus on terminology (ie, primary familial polycythemia but postrenal transplantation erythrocytosis). Polycythemias can be primary or secondary and can be inherited or acquired.

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

• Primary polycythemias are caused by somatic or germline mutations within hematopoietic stem cells or erythroid progenitors that result in an augmented response to erythropoietin. This response is inappropriate; that is, it is not a compensation for hypoxia.

• Secondary polycythemias are caused by either an appropriate (compensatory) or inappropriate increase in the red cell mass as a result of augmented levels of erythropoietin.

PRIMARY POLYCYTHEMIA

• The most common primary polycythemia, polycythemia vera, is a clonal acquired multipotential hematopoietic progenitor cell disorder discussed in Chap. 41. It is a myeloproliferative neoplasms.

Primary Familial and Congenital Polycythemia

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

• Affected persons may be misdiagnosed as having polycythemia vera.

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

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

• This condition is caused by a truncation of erythropoietin receptor and deletion of the negative regulatory cytoplasmic domain.

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

SECONDARY POLYCYTHEMIA (ERYTHROCYTOSIS)

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

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

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

Appropriate Secondary Polycythemias

High-Altitude Acclimatization

• There is a great variability in an individuals’ susceptibility to acute and chronic mountain sickness complications.

• Some populations such as Tibetans and Ethiopian dwellers of high mountains have a genetically determined resistance to these complications, whereas extreme polycythemia is often seen in Quechuas and Aymaras living at high-altitude (Andean natives).

• Acute mountain sickness involves:

  — Cerebral hypoxia is causal, and the condition may be life-threatening. Polycythemia does not occur.

  — Affected persons may have headaches, insomnia, palpitations, weakness, nausea, vomiting, and mental dullness, and they may develop pulmonary and cerebral edema.

  — Treatment is with oxygen, dexamethasone, and acetazolamide and if feasible rapid return to lower ...