This review will discuss evidence for the role of the erythropoietin (Epo)
receptor in the development of erythrocytosis and other hematological disor
ders, The possible causative role of mutations of other genes in the pathog
enesis of idiopathic erythrocytosis will be considered, Polycythemia vera (
PV) is a myeloproliferative disorder that is caused by an undefined stem ce
ll abnormality, characterized by a significant erythrocytosis, leukocytosis
, and thrombocytosis. However, erythrocytosis may arise from apparent (or r
elative) polycythemia in which the hematocrit is raised due to a low plasma
volume. In such cases the red cell mass is normal. A group of disorders wi
th increased red cell mass caused by stimulation of erythrocyte production
is known as secondary polycythemia, Investigation of such patients may reve
al a congenital abnormality such as high affinity hemoglobin or an acquired
abnormality caused, for example, by smoking, renal Vascular impairment, or
an Epo-producing tumor. Even after thorough examination there remains a co
hort of patients for whom no definite cause for the erythrocytosis can be e
stablished, A careful clinical history may reveal whether this idiopathic e
rythrocytosis is likely to be congenital and/or familial, in which case the
term "primary familial and congenital polycythemia" is sometimes applied,
Access to a range of laboratory investigations may define the molecular pat
hophysiology, We will now discuss how this process can be investigated. (C)
1999 Wiley-Liss, Inc.