A Review of Equine Polycythemia

Natasha A. Jones, DVM; Julie Webb, DVM, Bruce E. LeRoy, DVM, PhD

Class of 2007 (Jones) and Department of Pathology (Webb, LeRoy), College of Veterinary Medicine, University of Georgia, Athens, GA, 30602-7388

Signalment: Equine, Arabian mare

Presenting Problem: Respiratory distress

History: The patient was presented to the Veterinary Medical Teaching Hospital (VMTH) of the College of Veterinary Medicine at the University of Georgia for symptoms of respiratory distress. Prior to admission, the mare had a 3-5 day history of holding her head in a water bucket but not drinking. The referring veterinarian considered "choke" as the inciting cause of the respiratory distress and attempts to pass a nasogastric tube were unsuccessful. The horse has lost weight prior to admission and was nursing a 2-month-old filly. The mare resided in a paddock with 2 other mares with their foals, all of which appeared healthy. The mare's diet consisted of pellets, alfalfa hay, and she was kept on pasture. It was reported she was current on all vaccines and dewormed regularly. She had a history of allergies in the spring and summer that typically caused a nasal discharge.

Physical Exam: The patient was depressed, but alert and responsive with a body conditioning score of 1/5. Her weight was 640 lbs. and there was generalized muscle atrophy. Dehydration was estimated to be 10%. Increased respiratory sounds were noted along with bilateral mucopurulent nasal discharge and mucoid ocular discharge. The mare was unable to swallow. Her mucous membranes were pale pink and tacky with a capillary refill time of 2 seconds.

Diagnostic testing included a complete blood count, a biochemical profile including bile acids and blood gas analysis, radiographs of the upper airway and esophagus, and thoracic ultrasound. A PCR-based Salmonella assay was performed, as were ELISAs for clostridial antigens, and fecal samples were submitted for aerobic and anaerobic culture. An endoscopic evaluation of the upper airway and a bone marrow aspirate were also performed. Serum erythropoietin concentrations were measured.

Laboratory data + (abnormal findings shaded with grey)

**: Fibrinogen result was verified
*ND: not done, unable to perform differential due to poor cytomorphology
ND: not done
#: total protein was verified
+: serial chemistries and complete blood counts were performed during hospitalization.

Additional tests: During 9 days of hospitalization, the packed cell volume ranged between 40% and 72%. The total protein concentration during this time ranged between 5 g/dl and 11 g/dl. The bone marrow aspirates were poorly cellular and contained a few myeloid and erythroid precursors. There was no evidence of neoplasia or infectious agents in the marrow sample. The aerobic fecal culture showed heavy growth of Streptococcus equi subsp. equi and the anaerobic culture was negative. Fecal PCR for Salmonella and fecal ELISAs for both Clostridium difficile and perfringens were also negative. Upper airway endoscopy revealed guttural pouch empyema with chondroids present. Radiographs did not reveal evidence of pneumonia but there was an ovoid soft-tissue dense mass present in the retropharyngeal region compressing the pharynx. The post-mortem examination revealed abscesses with gram-positive cocci in the lungs of the horse, acute cortico-medullary infarctions in the kidneys, a neutrophilic myocarditis, a neutrophilic and hemorrhagic dermatitis with thrombi, and severe, diffuse edema of the cecum and large colon.

Master Problem List

1. Increased PCV, RBC count, and hemoglobin concentration (polycythemia) - see the following algorithms and Discussion

2. Thrombocytosis - most likely due to epinephrine-induced splenic contraction/physiologic thrombocytosis

3. Hyperfibrinogen - fibrinogen is an acute phase reactant and in this case is probably associated with inflammation, possibly associated with the respiratory tract or the gastrointestinal tract.

4. Increased creatinine concentration - most likely reflects prerenal azotemia due to severe dehydration. A renal component is also suggested by the renal infarcts found on necropsy.

5. Hyperproteinemia - most likely due to dehydration.

6. Hyperglycemia - likely due to glucocorticoid and epinephrine release secondary to stress, fear, and/or excitement.

7. Hypernatremia - most likely due to hypertonic dehydration, sweating, and insensible loss (the horse later developed colitis and diffuse watery diarrhea).

8. Increased anion gap - most likely due to lactic acidosis secondary to dehydration and poor peripheral perfusion.

9. Increased GGT activity - likely due to liver disease, possibly cholestatic.

10 Increased bile acid concentration - reflects liver disease and subsequent inability to recycle bile acids or cholestasis.

11. Increased erythropoietin concentration - may have been a response to a hypoxic state or an inappropriate increase due to an occult neoplasm.

Discussion

The mare presented to the VMTH approximately 10% dehydrated suggesting that relative polycythemia was likely. The decreased plasma volume led to a relative increase in the hematocrit, red blood cell count, and hemoglobin concentration. The increased total protein concentration with a normal A:G ratio (0.64) was also supportive of dehydration. Mechanisms of relative polycythemia include insensible loss(vomiting, diarrhea, diuresis, water deprivation, and/or excessive fever causing dehydration), internal loss from shock via increased vascular permeability, or loss by effusion into body cavities. However, the mare could have been excited and/or stressed due to her respiratory distress symptoms causing splenic contraction. Epinephrine-mediated splenic contraction causes high-PCV splenic blood (~80%) being released into the general circulation.¹ The mare was aggressively rehydrated with intravenous fluids (lactated Ringer's solution) over a 2 day period and serial PCVs and total protein concentrations were measured. There was a moderate drop in both PCV and TP initially suggesting that the relative polycythemia was corrected. In addition, the mare was administered cephalosporin antibiotics, glucocorticoids, non-steroidal anti-inflammatory agents, and DMSO to treat the streptococcal infection and a tracheostomy tube was inserted to relieve respiratory compromise.⁸

The polycythemia recrudesced shortly after initial treatment. Surgery was performed to remove inspissated pus and large chondroids from the guttural pouch in an attempt to relieve respiratory distress. Fluid therapy continued and a proton-pump inhibitor was administered to prevent gastric ulceration. Monitoring of serial PCVs and TPs revealed that the mare's PCV began to rise while the mare's TP concentration remained within the reference interval. This finding suggested that the polycythemia was no longer relative, but could be an absolute polycythemia. The mare exhibited no overt signs of dehydration and had been receiving aggressive intravenous fluid therapy since admission to the VMTH. Additionally, the mare's plasma protein concentration was within the reference interval for the remainder of mare's hospitalization.

Absolute polycythemia is a non-spurious increase in PCV of a normally hydrated animal and has both primary and secondary causes. Primary absolute polycythemia is rare in horses and is caused by the neoplastic erythrocytic disorder known as polycythemia vera.¹ Polycythemia vera is a myeloproliferative disease resulting in clonal proliferation of mature erythrocytes and occurs in the absence of an increase in concentration of erythropoietin (EPO).^2,6 A bone marrow aspirate was performed to evaluate the erythropoietic response in the mare, but was found to be non-diagnostic due to low cellularity. In polycythemia vera, the bone marrow is often hypercellular but the M:E ratio may be normal. EPO concentration were measured and found to approach 4x the upper limit of the reference interval.

An increase in EPO concentration suggests that the horse had developed an absolute secondary polycythemia (see diagnostic algorithm). An appropriate increase in EPO occurs in response to chronic hypoxic conditions such as high altitude, chronic pulmonary disease, or cardiac disease.¹ The mare did not exhibit signs of these conditions and the presenting history did not support this cause of polycythemia. Blood gas analysis revealed the mare's arterial oxygen saturation was within the reference interval.Therefore, this mare appears to have developed an absolute secondary polycythemia due to inappropriate secretion of EPO.

Causes of absolute secondary inappropriate polycythemia include hydronephrosis, renal cysts, and EPO-secreting neoplasms (such as renal carcinomas and hepatomas).¹ Polycythemia can also be associated with neoplasia as a paraneoplastic syndrome (PNS), but is relatively uncommon. Paraneoplastic polycythemia has been described in domestic animals with renal tumors, lymphoma, liver tumors, nasal fibrosarcomas, and transmissible venereal tumors.² Hepatoblastoma is rare hepatic tumor that can develop in juvenile domestic animals and humans that have an erythrocytosis-associated paraneoplastic syndrome. In fact, some hepatoblastomas may be mistakenly diagnosed as polycythemia vera due to an increase in alpha-fetoproteinemia and erythropoietin that are naturally secreted by fetal liver cells.³ The post-mortem examination found acute renal cortico-medullary infarctions but made no mention of other findings consistent with primary or metastatic neoplasia. The classification of polycythemia in this mare is further complicated by the development of colitis and watery, profuse diarrhea thought to be associated with antibiotics given to treat the streptococcal infection. Diarrhea could have contributed to a mixed polycythemia by introducing dehydration and loss of plasma proteins.

Treatment of the polycythemia in the mare included serial phlebotomy, heparin to prevent DIC and clotting, and plasma transfusions, each of which seemed to decrease the mare's PCV once treatment was instituted. Due to a lack of satisfactory response to treatment, the mare was ultimately euthanized at the owner's request.

Algorithm for Polycythemia in a Horse^6,7

Algorithm for Absolute polycythemia in a Horse⁶

References

1. Brockus CW, Andreasen CB. Erythrocytes. In Latimer KS, Mahaffey EA, Prasse KW (eds): Duncan & Prasse's Veterinary Laboratory Medicine: Clinical Pathology, 4th ed. Ames, Iowa State Press, pp 42-4. 2003.

2. Young KM, MacEwen EG. Polycythemia vera. In Withrow SJ, MacEwen EG (eds): Small Animal Clinical Oncology, 3rd ed. W B Saunders Co., Philadelphia. pp. 616-617, 2001.

3. Knottenbelt, DC: Neoplasie interne: linfosarcomi, 9 Congresso Nazional Multisala SIVE, Domenica, 2 Febbraio 2003, 16.30.

4. Lennox TJ, Wilson JH, Hayden DW, Bouljihad M, Sage AM, Walser MM, Manivel JC. Hepatoblastoma with erythrocytosis in a young female horse. Journal of the American Veterinary Medical Association 216(5):718-721, 2000.

5. Beech J, Bloom JC, Hodge TG. Erythrocytosis in a horse. Journal of American Veterinary Medical Association 184(8):986-989, 1984.

6. Brobst, DF. The Veterinary Clinics of North America: Equine Practice Clinical Pathology: Hematologic Values in Horses and Interpretation of Hematologic Data, pp. 461-484, 1987.

7. Cowell RL, Tyler RD (eds): Diagnostic Cytology and Hematology of the Horse, 2nd ed., Mosby Inc., p 209, 2002.

8. Plumb, DC (ed): Plumb's Veterinary Drug Handbook, 5th ed., Blackwell Publishing, 2005.

Acknowledgement

The image "Seahorse II" by Melody Mumma © 2006 is from her website Artwork of Melody Mumma and is used with perission. This piece of Equestrian Art captures an Arabian Horse trotting along the seashore under the glow of a beautiful sunset.

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