Abstract

Neutrophils are one of the initial lines of protection against pathogens. When their concentrations in the blood decrease markedly, animals become highly susceptible to infections.¹⁰ Neutropenia is caused by increased demand, increased consumption, decreased production, or destruction of neutrophils or their precursors.¹ In domestic animals, causes of neutropenia include infectious diseases such as viral and rickettsial infections, bacterial pneumonia or sepsis, drug reactions, primary bone marrow disease, and immune-mediated disease.^1,9 Neutropenia has been reported in cetaceans secondary to systemic sulfa^2,6 and ketoconazole use⁴ and chronic, severe infection.⁸ Filgrastim (Neupogen®, Amgen Manufacturing, Ltd., Thousand Oaks, CA, USA), is a human recombinant granulocyte colony-stimulating factor that is effective in increasing peripheral neutrophil counts in a number of species.^3,5,7 We report the use of filgrastim to treat neutropenia in three cetacean species (killer whale [Orcinus orca], n=6; bottlenose dolphin [Tursiops truncatus], n=4; and beluga whale [Delphinapterus leucas], n=1) ranging in age from one week to greater than 24 years. In most cases, the cause of neutropenia was undetermined (n=8). Bacterial septicemia (n=1) and drug reaction to systemic sulfa (n=2) were identified causes. In all but two instances, neutrophil counts increased within 24–48 hours of one dose of filgrastim (1–7 µg/kg). In the majority of cases, the response was characterized by an initial rise in band neutrophils followed by an increase in mature neutrophils. The number of doses of filgrastim administered, intensity of monitoring, and degree and duration of response varied among cases. No adverse reactions were seen.

Acknowledgments

The authors thank the animal training, animal care, and veterinary services departments at SeaWorld Orlando, SeaWorld San Antonio, and SeaWorld San Diego for their care of the animals.

Literature Cited

1.  Brown RM, Rogers KS. Neutropenia in dogs and cats. Compend Contin Educ Pract Vet. 2001;23:534–542.

2.  Cornell LH. Drug induced agranulocytic leukopenia in cetaceans. In: Proceedings from the American Association of Zoo Veterinarians. 1978:48–51.

3.  Cullor JS, Fairley N, Smith WL, Wood SL, Dellinger JD, Inokuma MS, Souza LM. Hemogram changes in lacatating dairy cows given human recombinant granulocyte colony-stimulating factor (r-MethuG-CSF). Vet Pathol. 1990;27:311–316.

4.  Fothergill M, Jogessar VB. Haematological changes in two Lagenorhynchus obscurus treated with ketoconazole. Aquat Mamm. 1986;12:87–91.

5.  Fulton R, Gasper PW, Ogilvie GK, Boone TC, Dornsife RE. Effect of recombinant human granulocytic colony-stimulating factor on hematopoiesis in normal cats. Exp Hematol. 1991;19:759–767.

6.  McBain J. Sulfamethoxazole toxicity in three killer whales. In: Proceedings from the International Association Aquatic Animal Medicine. 1984:38.

7.  McKenzie EC, Tornquist SJ, Gorman ME, Cebra CK, Payton E. Hematologic effects of subcutaneous administration of recombinant human granulocyte colony-stimulating factor (filgrastim) in healthy alpacas. Am J Vet Res. 2008;69:770–776.

8.  Medway W, Geraci JR. Clinical pathology of marine mammals. In: Fowler ME, ed. Zoo and Wild Animal Medicine. 2nd ed. Philadelphia, PA: WB Saunders Co.; 1986:791–797.

9.  Tornquist SJ, Rigas J. Interpretation of ruminant leukocyte responses. In: Weiss DJ, Wardrop KJ, eds. Schalm’s Veterinary Hematology. 6th ed. Ames, IA: Wiley-Blackwell; 2010:307–313.

10.  Weiss DJ, Ramaiah SK, Walcheck B. Neutrophil distribution and function. In: Weiss DJ, Wardrop KJ, eds. Schalm’s Veterinary Hematology. 6th ed. Ames, IA: Wiley-Blackwell; 2010:258–274.