Polycythemia

Introduction

Erythrocytosis is a relative or absolute increase in the number of circulating RBC, resulting in a PCV increased above reference ranges. Polycythemia is frequently used synonymously with erythrocytosis; however, polycythemia may imply leukocytosis and thrombocytosis, as well as erythrocytosis.

Relative Erythrocytosis

Relative erythrocytosis is an increase in RBC numbers without an increase in total RBC mass. Usually, this is caused by loss of plasma volume with resultant hemoconcentration, as seen in severe dehydration attributable to vomiting and diarrhea. Alternatively, a mild, transient form of relative erythrocytosis unassociated with clinical signs may develop in dogs when fear or excitement causes splenic contraction with release of RBC into the circulation.

Absolute Erythrocytosis

Absolute erythrocytosis, defined as increased RBC numbers because of increased RBC mass, develops from primary or secondary causes. Primary erythrocytosis (polycythemia vera) is a myeloproliferative disease of unknown cause that has been reported in dogs, cats, cattle, and horses. RBC production is dramatically increased, while serum erythropoietin (EPO) activity typically is low or low-normal. Secondary erythrocytosis, in contrast, generally develops from excessive production of EPO. If the EPO is secreted because of systemic hypoxia, then the resultant erythrocytosis is an appropriate compensatory response. This may be seen with severe pulmonary disease or heart anomalies resulting in right-to-left shunting with blood bypassing the lungs (eg. reversed patent ductus arteriosus, tetralogy of Fallot). If EPO production increases without systemic hypoxia, then the response is inappropriate. EPO-secreting tumors of the kidneys or other organs, or non-neoplastic renal disorders resulting in local hypoxia with EPO production, may cause inappropriate erythrocytosis. Another type of secondary erythrocytosis, called endocrinopathy-associated erythrocytosis, results from hormones other than EPO (eg. cortisol, androgen, thyroxine, growth hormone) that stimulate erythropoiesis. The mild erythrocytosis in dogs with adrenocortical hyperactivity or in cats with hyperthyroidism or acromegaly is insufficient to cause clinical signs.

Clinical Signs

Clinical signs of absolute erythrocytosis include red mucous membranes, bleeding tendencies, polyuria, polydipsia, and neurologic disturbances (ataxia, weakness, seizures, blindness, behavioral change). On retinal examination, dilated, tortuous vessels may be visualized. These collective clinical features are attributed to hyperviscosity from the increased RBC mass.

Diagnosis

The dehydration and hemoconcentration of relative erythrocytosis may be identified by clinical findings (dry mucous membranes, loss of skin turgor), laboratory variables (hyperproteinemia, prerenal azotemia), and response to rehydration. Excitable dogs with mild erythrocytosis attributed to splenic contraction usually have normal PCV on subsequent blood samples collected less stressfully. Sighthounds (eg. Greyhounds) normally have mild erythrocytosis compared with standard canine reference ranges.

With absolute erythrocytosis, serum EPO determinations have been recommended to differentiate primary from secondary causes. Unfortunately, considerable overlap exists in EPO activity among normal animals, animals with primary erythrocytosis, and animals with secondary erythrocytosis. Furthermore, current availability of validated EPO assays for companion animals is limited. Routine examination of bone marrow is not useful to distinguish primary from secondary erythrocytosis because both conditions show erythroid hyperplasia. As a result, primary erythrocytosis usually is diagnosed by eliminating secondary causes.

To investigate types of secondary erythrocytosis, assessment of tissue oxygenation may be helpful. Arterial blood pO2 <80 mmHg and pulse oximetry oxygen saturation <90–95% are consistent with the hypoxemia and tissue hypoxia of appropriate compensatory response.