Chapter 29: Polyclonal Polycythemias (Primary and Secondary)

INTRODUCTION

• Polycythemia (also known as erythrocytosis) is characterized by an increased red cell blood volume. Polycythemias can be primary or secondary and either inherited or acquired.

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

• Primary polycythemias are caused by somatic or germline mutations causing changes within hematopoietic stem cells or erythroid progenitors causing an augmented response to erythropoietin.

• Secondary polycythemias are caused by either an appropriate 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. 43.

Primary Familial and Congenital Polycythemia

• Autosomal dominant disorder, with normal leukocytes and platelets.

• Many affected persons are misdiagnosed as having polycythemia vera.

• Always low erythropoietin level (see Fig. 29–1).

• Erythroid progenitors in in vitro cultures are hypersensitive to erythropoietin but do not grow independent of erythropoietin.

• Caused by a truncation of erythropoietin receptor and deletion of 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)

• A group of disorders with 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 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, Aymaras and Quechua natives of High Andes, and Ethiopian dwellers of high mountains have a genetically determined resistance to these complications.

• Acute mountain sickness:

  — Caused by cerebral hypoxia and may be life-threatening. Polycythemia does not occur.

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

  — Treatment is with oxygen, dexamethasone, and acetazolamide and/or rapid return to lower altitude.

• Chronic mountain sickness:

  — Occurs after prolonged exposure to high altitudes; there appears to be a genetic predisposition.

  — Characterized by marked polycythemia, cyanosis, plethora, pulmonary hypertension, clubbing of the fingers, and signs of right heart failure.

  — Treatment with the angiotensin-converting enzyme inhibitor enalapril has been reported to be effective.

  — A return to a normal state develops slowly.

Pulmonary Disease

• Associated with cyanosis, clubbing, ...