Peer-reviewed veterinary case report
Dog red blood cell enzyme levels and azathioprine bone marrow side
By Rodriguez, Damon B et al.·Published in Journal of veterinary internal medicine·2004·Department of Clinical Sciences, United States·View original on PubMed →
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Original publication title: Relationship between red blood cell thiopurine methyltransferase activity and myelotoxicity in dogs receiving azathioprine.
- Species:
- dog
Plain-English summary
A group of dogs receiving azathioprine, a medication often used to treat autoimmune diseases, were studied to see if their red blood cell enzyme activity could predict side effects like low white blood cell counts. The researchers found that dogs with intermediate enzyme activity experienced a drop in their neutrophil counts after four weeks of treatment, while those with high enzyme activity did not show significant changes. However, even dogs with a history of severe side effects had varying enzyme levels, indicating that other factors may also contribute to these reactions. This suggests that monitoring enzyme activity alone may not be enough to predict myelotoxicity in dogs on azathioprine.
People also search for: dog azathioprine side effects · low white blood cell count in dogs · dog neutrophil count treatment
Abstract
Thiopurine methyltransferase (TPMT) produces inactive metabolites of azathioprine and, in humans, has a variable amount of activity. Humans with low TPMT activity commonly develop myelotoxicity when receiving azathioprine. Our study sought to characterize the distribution of TPMT activity in a population of dogs and to determine whether the pretreatment knowledge of red blood cell (RBC) TPMT activity could predict myelotoxicity in dogs receiving azathioprine. RBC TPMT activity was measured in 299 healthy dogs, and 9 dogs that represented a wide range of enzyme activity received azathioprine at a standard therapeutic dose for 30 days. TPMT activity in healthy dogs was log normally distributed and varied over an approximately 7-fold range. Geometric mean, minimum, and maximum RBC TPMT activities were 37.1, 16.3, and 115 nmol per gram of hemoglobin (gHb) per hour, respectively. TPMT deficiency was not identified. Two populations of TPMT activity in dogs were detected by statistical modeling (commingling analysis). Dogs with intermediate TPMT activity (14-38 nmol/gHb/h) receiving azathioprine had significantly lower neutrophil counts during week 4 than during weeks 0-3, whereas those with high activity (>39 nmol/gHb/h) did not have a significant change in neutrophil count. An analysis of TPMT activity in 6 dogs with a history of azathioprine-associated myelotoxicity in a clinical setting revealed either intermediate or high TPMT enzyme activity in all dogs, suggesting that TPMT activity, as measured in RBCs, is not the sole cause of severe azathioprine-associated myelosuppression in dogs.
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Search related cases →Original publication on PubMed: https://pubmed.ncbi.nlm.nih.gov/15188821/