Diagnosis considered when hemoglobin exceeds 18.5 gm/dL or hematocrit of 52% in men, and 16.5 gm/dL or hematocrit of 48% (Tefferi A).
Primary and secondary types distinguished by determining the level of serum erythropoietin, or the presence or absence of V617F mutation of the JAK2 gene, and bone marrow biopsy morphological analysis.
In primary polycythemia erythroid progenitors are intrinsically hyperproliferative and can grow without erythropoietin, or at a erythropoietin concentration that is lower than normal.
Primary polycythemias include findings of of low levels of 2,3 diphosphoglycerate in red cells resulting from a congenital disorder of 2,3 DPG synthesis.
When less oxygen is released into the tissues from hemoglobin, the body compensates by increasing erythropoiesis until sufficient oxygen is delivered to the tissues.
Secondary polycythemia can be inherited, caused by mutations in genes have the hypoxia sensing pathway or by local variants with a high hemoglobin affinity for oxygen.
In spurious polycythemia the red cell mass in the body is normal but the plasma level is decreased.
One form of spurious polycythemia is Gaisbock syndrome, which occurs primarily an obese men..
Both types of polycythemia are associated with thromboembolism.
Symptoms may or may not be present.
Splenomegaly more common in primary polycythemia.
Secondary polycythemia characterized by hypoxia driven or hypoxia independence.
Symptoms of erythrcytosis are highly variable, depending upon the underlying cause.
Erythrocytosis may cause no symptoms at all, or may be highly symptomatic and detrimental to health.
Symptoms include pruritus, erythromalagia, thromboses, and gout.
Risk of transformation to myelofibrosis in patients with polycythemia vera is approximately 15%.
Hypoxia driven types of secondary polycythemia include: COPD, right to left cardiopulmonary shunting, chronic exposure to carbon monoxide, smoking abuse, obstructive sleep apnea, hemoglobin abnormalities with high oxygen binding affinity and red blood cell enzyme deficiencies, and renal artery stenosis.
Hypoxia independent causes of secondary polycythemia, often with elevated erythropoietin levels include: hepatomas, renal cell carcinoma, pheochromocytomas, hemangioblastomas and uterine leiomyomas.
Chuvash polycythemia, a familial autosomal recessive polycythemia is related to specific mutations in the VHL tumor suppressor gene located on chromosome 3 and results in decreased degradation of hypoxia-inducible factor 1 alpha protein.
Smoking related secondary polycythemia results from carboxyhemoglobin induced increased red blood cell mass with decreased plasma volume, concurrently.
The carbon monoxide enters the bloodstream when cigarettes or smoked as heme iron affinity is 200 times greater than that of oxygen and forms carboxyhemoglobin.
Carboxyhemoglobin levels of greater than 4% can cause erythrocytosis as functional hemoglobin is reduced proportionately and oxygen delivery to tissues is impaired.