Journal of Veterinary Emergency and Critical Care 28(2) 2018, pp 130–139
Plasma ammonia concentration after
L-asparaginase therapy in 27 dogs with
high-grade lymphoma or leukemia
Abbie L. Speas, DVM; Sarah E. Lyles, DVM, DACVIM; Kimberly A. Wirth, DVM, DACVIM;
Christine E. Fahey, DVM, DACVIM; Kelvin Kow, DVM, MS, DACVIM; Amandine T. Lejeune, DVM,
DACVIM and Rowan J. Milner, BVSc (Hons), MMedVet, PhD, DACVIM, DECVIM
Objectives – To establish the occurrence of increased plasma ammonia concentration after L-asparaginase (L-
asp) administration in dogs with high-grade lymphoma or leukemia; to identify risk factors for the development
of hyperammonemia after L-asp administration; and to determine occurrence of adverse events related to
Design – Prospective case controlled study of sequentially enrolled dogs between May 2011 and March 2012.
Setting – A university veterinary teaching hospital.
Animals – Twenty-seven dogs with high-grade lymphoma or leukemia.
Interventions – All dogs received L-asp intramuscularly at a median dose of 400 IU/kg.
Measurements and Main Results – Plasma ammonia concentrations were measured at baseline, 16 hours, and
48 hours after L-asp therapy. Clinicopathological abnormalities were assessed to determine risk factors for the
development of hyperammonemia. Adverse events following L-asp were recorded. Median plasma ammonia
concentrations at baseline, 16 hours, and 48 hours were 26 mol/L (44 g/dL), 98 mol/L (166.9 g/dL),
and 67 mol/L (114 g/dL), respectively. Median plasma ammonia concentrations at 16 and 48 hours after
administration were signiﬁcantly increased compared to baseline. Six dogs had adverse events following L-asp
administration. No signiﬁcant clinical signs were noted that could clearly be attributed to hyperammonemia.
No risk factors for developing hyperammonemia were identiﬁed; however, there was a positive correlation
between the development of hyperammonemia at 16- and 48-hour time points.
Conclusions – Subclinical hyperammonemia in dogs with lymphoma or leukemia after L-asp administration
appears to be common. No risk factors were identiﬁed for the development of hyperammonemia after L-asp
treatment, and severe adverse events were rare.
(J Vet Emerg Crit Care 2018; 28(2): 130–139) doi: 10.1111/vec.12695
asparaginase, chemotherapy, Elspar, hyperammonemia, lymphosarcoma, neoplasia
AE adverse event
ALT alanine transaminase
From the Small Animal Department of Clinical Sciences, College of Veteri-
nary Medicine, University of Florida, Gainesville, FL 32610.
The authors declare no conﬂicts of interest.
This study was funded by the University of Florida CVM resident research
Presented at Veterinary Cancer Society Annual Conference, October, 2015 in
Address correspondence and reprint requests to Dr. Rowan Milner, Depart-
ment of Small Animal Clinical Sciences, University of Florida College of
Veterinary Medicine, PO Box 100126, Gainesville, FL 32610, USA.
Submitted December 31, 2015; Accepted June 14, 2016.
ALP alkaline phosphatase
cPLI canine pancreatic lipase immunoreactivity
L-asparaginase (L-asp) is an enzyme commonly used in
both human and veterinary medicine as part of multi-
agent chemotherapy protocols for lymphoproliferative
L-asp works by depleting the peripheral
blood of asparagine, a necessary amino acid for survival
of lymphoid cells. While normal lymphoid cells are able
to produce their own asparagine, neoplastic lymphoid
cells cannot, leaving them reliant upon extracellular
Veterinary Emergency and Critical Care Society 2018