Find information on medical topics, symptoms, drugs, procedures, news and more, written for the health care professional.

* This is the Professional Version. *

Secondary Erythrocytosis

(Secondary Polycythemia)

by Jane Liesveld, MD, Patrick Reagan, MD

Secondary erythrocytosis is erythrocytosis that develops secondary to circulating erythropoiesis-stimulating substances.

In secondary erythrocytosis, only the RBC line is increased, whereas in polycythemia vera (see Polycythemia Vera), RBCs, WBCs, and platelets may be increased. Any elevation of Hb or Hct above normal values for age and sex is considered erythrocytosis.

Common causes of secondary erythrocytosis include

  • Smoking

  • Chronic arterial hypoxemia

  • Tumors (tumor-associated erythrocytosis)

Less common causes include certain congenital disorders such as

  • High O 2 -affinity hemoglobinopathies

  • Erythropoietin receptor mutations

  • Chuvash polycythemia (in which a mutation in the VHL gene affects the hypoxia-sensing pathway)

  • Proline hydroxylase 2 and hypoxia-inducible factor 2 α ( HIF-2α ) mutations

Spurious erythrocytosis may occur with hemoconcentration (eg, due to burns, diarrhea, or diuretics).

In patients who smoke, reversible erythrocytosis results mainly from tissue hypoxia due to elevation of blood carboxyhemoglobin concentration; levels often normalize with smoking cessation.

Patients with chronic hypoxemia (arterial Hb O 2 concentration < 92%), typically due to lung disease, right-to-left intracardiac shunts, renal transplantation, prolonged exposure to high altitudes (see Altitude Diseases), or hypoventilation syndromes, often develop erythrocytosis. The primary treatment is to alleviate the underlying condition, but O 2 therapy may help, and some degree of phlebotomy may decrease viscosity and alleviate symptoms. Because in some cases the elevated Hct is physiologic, phlebotomy may cause harm because it decreases tissue oxygenation.

Tumor-associated erythrocytosis can occur when renal tumors, cysts, hepatomas, cerebellar hemangioblastomas, or uterine leiomyomas secrete erythropoietin . Removal of the lesion may be curative.

High O 2 –affinity hemoglobinopathies are very rare. This diagnosis is suggested by a family history of erythrocytosis; it is established by measuring the P 50 (the partial pressure of O 2 at which Hb becomes 50% saturated) and, if possible, determining the complete oxyhemoglobin dissociation curve. Standard Hb electrophoresis may be normal and cannot reliably exclude this cause of erythrocytosis.

Evaluation

Tests done when erythrocytosis is present include

  • Arterial O 2 saturation

  • Serum erythropoietin levels

  • P 50

A low or low-normal serum erythropoietin level suggests PV. Patients with hypoxia-induced erythrocytosis have an elevated level or inappropriately normal level for their elevated Hct. Patients with tumor-associated erythrocytosis typically have elevated erythropoietin levels. Patients with elevated erythropoietin levels or microscopic hematuria should undergo abdominal imaging, CNS imaging, or both to seek a renal lesion or other tumor sources of erythropoietin .

P 50 measures the affinity of Hb for O 2 ; a normal result excludes a high-affinity Hb (a familial abnormality) as the cause of erythrocytosis.

* This is a professional Version *