Diagnosis and Treatment of Erythrocytosis

European Haematology, 2010;4:55-8

Abstract:

An erythrocytosis arises when the red cell mass is increased. This can be due to a primary intrinsic defect in the erythroid progenitor cells or secondary to erythropoietin production from some source. Primary and secondary causes can be congenital or acquired. Rare, primary congenital defects are due to mutations leading to truncation of the erythropoietin receptor. The main acquired, primary erythrocytosis is polycythaemia vera. Among the congenital secondary causes, a number of defects in the genes in the oxygen-sensing pathway have recently been described, which lead to a secondary erythrocytosis. An extensive list of acquired secondary causes needs to be considered. A number of patients do not have an identifiable cause of erythrocytosis and are therefore described as having idiopathic erythrocytosis. Investigation should commence with careful clinical evaluation. Determination of the erythropoietin level is then a first step to guide the further direction of investigation. In those with congenital defects, a number of serious thromboembolic events have been described, but there is little information available about outcomes in these individuals and, therefore, no evidence to guide management. In this group, consideration should be given to the use of venesection to attain an achievable haematocrit level, and also low-dose aspirin therapy.
Keywords: Erythrocytosis, erythropoietin, prolyl hydroxylases, von Hippel-Lindau protein, hypoxia-inducible factor, idiopathic erythrocytosis
Disclosure: The author has no conflicts of interest to declare.
Received: November 23, 2009 Accepted February 18, 2010 Citation European Haematology, 2010;4:55-8
Correspondence: Mary Frances McMullin, Department of Haematology, ‘C’ Floor, Belfast City Hospital, Queen’s University Belfast, Lisburn Road, Belfast, BT9 7AB, Northern Ireland. E: m.mcmullin@qub.ac.uk

Red cells constitute the vast majority of the cells in circulation in the human body. The amount of red cells has an influence on the viscosity of the blood. Red cell production is under exquisitely sensitive control. Any disruption of this system can lead to an increase in red cell production – erythrocytosis – leading to increased viscosity, with clinical consequences.
Erythrocytosis
An absolute erythrocytosis is present when there is an increase in the red cell mass over 125% of that predicted for the individual’s body mass.1 This can be measured. If the haematocrit (Hct) level is over 0.60 in a male or 0.56 in a female, the red cell mass has been shown to be increased, and it can be assumed in these cases that there is an absolute erythrocytosis. Haemoglobin (Hb) above 18.5g/dl or Hct above 0.52 in a male are judged to be elevated and warrant further investigation. The equivalent figures for females are 16.5g/dl and 0.48. These numbers do not always translate to an absolute erythrocytosis, as has been shown in a comparative study,2 and it may be necessary to formally measure the red cell mass to establish the presence of an absolute erythrocytosis. Red cells contain haemoglobin, which supplies oxygen to the tissues. The oxygen supply to the tissues is under fine control and the hormone produced in response to hypoxia is erythropoietin (EPO). EPO is mainly produced by the kidneys. Any fall in oxygen levels in the tissues in the kidneys will result in increased EPO production and, consequently, an erythrocytosis.
Classification of Erythrocytoses
When an erythrocytosis is established, it is necessary to look for a cause. An absolute erythrocytosis can be classified depending on its aetiology. Erythrocytoses are classified as primary if there is an intrinsic defect in the erythroid progenitor cells in the bone marrow, or secondary if the increased red cell mass results from factors external to the erythroid progenitor cell (i.e. increased EPO production from any cause, driving red cell production).
Primary and secondary erythrocytoses can be subdivided into congenital and acquired groups (see Table 1). Primary erythrocytoses will have an EPO level below normal, as the intrinsic defect in the progenitor is responsible for the red cell production, and the physiological response to this is depression of EPO levels. In secondary erythrocytoses, EPO levels will be normal (inappropriate for a raised Hb) or elevated as the EPO is driving the erythrocytosis.
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Keywords: Erythrocytosis, erythropoietin, prolyl hydroxylases, von Hippel-Lindau protein, hypoxia-inducible factor, idiopathic erythrocytosis