Erythrocytosis in Horses

Dehydrated animals experience a reduced proportion of plasma due to a loss of water volume. In this manner, dehydration results in a relative erythrocytosis because the increase in red cells is attributed to reduced plasma volume (3). 

Treatment relies on correcting the dehydration along with treating any underlying conditions resulting in accelerated water loss or water deprivation. The erythrocytosis is expected to resolve when the patient is rehydrated.

The equine spleen is capable of sequestering a large number of red cells that can be released when the animal is excited, fearful, in pain, or exercising. In fact, splenic contraction can increase the hematocrit substantially, approximately 40% above the patient’s baseline on average (4). 

The PCV may remain in the reference interval or increase above the reference interval, depending on the original red cell concentration.

An erythrocytosis secondary to splenic contraction is not expected to be associated with a concurrent panhyperproteinemia or clinical signs of dehydration. However, laboratory changes associated with catecholamine (ie, epinephrine, norepinephrine) release may occur, such as mild to moderate hyperglycemia, mild mature neutrophilia and lymphocytosis, and/or a mild to moderate thrombocytosis.

Because the effects of splenic contraction are transient, the PCV and other CBC changes should return to baseline within 40–60 minutes.

Primary absolute erythrocytosis is considered a diagnosis of exclusion reserved for animals with a persistent erythrocytosis without evidence of dehydration, suspected splenic contraction, or identifiable causes for a secondary absolute erythrocytosis (2). 

In humans, dogs, and cats, the serum erythropoietin concentration is typically within the reference interval or decreased (2). A mutation in the Janus kinase 2 (JAK2) gene has been described in humans and dogs (5, 6). 

Primary absolute erythrocytosis is a very rare diagnosis in horses and has only been described twice in the literature as isolated case reports.

Secondary absolute erythrocytoses can be further categorized as “appropriate” or “inappropriate.” In humans, diagnosis and treatment of secondary absolute erythrocytoses are directed to identifying and treating the underlying causes (6).

An appropriate secondary absolute erythrocytosis occurs when there is increased release of erythropoietin in an attempt to improve the blood’s oxygen-carrying capacity. This may occur with cardiac or respiratory disease, high altitudes, or hemoglobin disorders (1). In this way, the increased production of erythropoietin is considered an appropriate response to poor tissue oxygenation.

Hypoxemia with a PaO₂ < 80-mmHg and O₂ saturation < 92% is sufficient to induce an erythrocytosis (1, 7).

In horses, an appropriate secondary absolute erythrocytosis is most often connected with congenital cardiac defects associated with right to left shunting or lung disease, including chronic pneumonia or pleuropneumonia (1, 7). However, it should be noted that most equine lung conditions are not severe enough to cause hypoxemia sufficient to result in an erythrocytosis (1).

Inappropriate secondary absolute erythrocytosis is typically a paraneoplastic finding attributed to autonomous synthesis of erythropoietin or prostaglandins enhancing the actions of erythropoietin by a neoplasm or as a response to renal hypoxia (1, 8). 

In horses, reported associated neoplasms include hepatoblastoma, lymphoma, hepatocellular carcinoma, and a metastatic carcinoma (9, 10, 11, 12, 13).

Administration of erythropoietin or erythropoietin-like compounds can also result in a secondary inappropriate erythrocytosis.

Although the usage of erythropoietin, erythropoietin-like compounds, and agents affecting erythropoiesis is prohibited by the Horseracing Integrity and Safety Authority and Association of Racing Commissioners International, they are still illegally and unethically used.

For example, a 10-year-old endurance horse developed an erythrocytosis (PCV 58%) after continuous supplementation with several hematinic components and was presented for poor performance, including tiredness during training, inability to complete in races, and colic (14). Discontinuation of the compounds was recommended, and several months later, the horse was successfully competing over longer distances with a resting PCV of 36% (14). 

This case illustrates that while an erythrocytosis should theoretically enhance oxygen-carrying capacity, in practice, it can increase blood viscosity such that it negates any improvements to the oxygen-carrying capacity (1).