Acute hyperammonemia after L‐asparaginase administration in a dog

Abstract

The purpose of this report is to describe the development of severe hyperammonemia after L-asp therapy in a dog, which has not been previously reported in the literature. Given the rapid progression and fatal outcome observed in this case, early recognition may be crucial for management and treatment of this complication.

Plasma ammonia concentration after L‐asparaginase therapy in 27 dogs with high‐grade lymphoma or leukemia

“…Hyperammonemia after L‐asp administration has been reported in people and its clinical implications are severe and rapidly progressive, but plasma ammonia concentrations after L‐asp have not been fully evaluated in dogs. Only 1 case report has documented development of severe hyperammonemia (1060 μmol/L [1805 μg/dL]) in a dog leading to a comatose state and subsequent cardiopulmonary arrest . In a study evaluating the pharmacokinetics of L‐asp in dogs after IM or SQ administration, increased levels of aspartic acid, glutamine, and glutamic acid were found 1 week after treatment with L‐asp; however, plasma ammonia concentrations were not evaluated in that study .…”

“…While dose reductions for hepatically metabolized chemotherapeutics such as vincristine are recommended for dogs with liver dysfunction, it is unknown whether dose reductions are also needed for L‐asp. Given the previous report of fatal hyperammonemia in a Beagle dog, it was thought that the additional ammonia produced by L‐asp may not be easily cleared by dogs with hepatic dysfunction. However, in the current study, dogs with increased liver values did not experience a significant increase in plasma ammonia concentration compared to dogs with normal liver values.…”

“…While normal lymphoid cells are able to produce their own asparagine, neoplastic lymphoid cells cannot, leaving them reliant upon extracellular asparagine reserves . Adverse reactions to L‐asp are not common in dogs; however, previously reported reactions include anaphylaxis, pancreatitis, decreased protein synthesis, coagulopathies, hepatotoxicity, and more recently, hyperammonemic encephalopathy . Hyperammonemic encephalopathy is a rare complication of intensive chemotherapy in people characterized by increased serum ammonia concentration, normal liver function tests, and respiratory alkalosis .…”

“…To the authors’ knowledge, in veterinary medicine, only 1 case of hyperammonemia after L‐asp administration in a dog has been reported to date . In that case, Lyles et al reported on a dog that developed severe hyperammonemia within 24 hours of receiving L‐asp and subsequently died.…”

Prospective evaluation of the safety of compounded bulk material L‐asparaginase in dogs with lymphoma

“…Other adverse effects of LASP are thought to result from contamination with bacterial endotoxin or inhibition of protein synthesis secondary to asparagine depletion. These AE have been documented in people, but only rarely reported in dogs, and include pancreatitis, abnormal liver function tests, vague gastrointestinal signs, and decreased synthesis of proteins such as albumin and clotting factors (Rogers et al, 1992;Ogilvie et al, 1994;Chabner & Friedmann, 2011;Lyles et al, 2011;Schleis et al, 2011). One dog in this study was diagnosed with Table 2.…”