BACKGROUND: Immune thrombocytopenia (ITP) is a common cause of severe thrombocytopenia in dogs. The pathogenesis of nonassociative, primary ITP (pITP) appears complex, with ill-defined thrombopoietic response.
OBJECTIVE: Develop an immunoassay to measure plasma canine thrombopoietin (TPO) concentration and characterize TPO concentrations in dogs with pITP.
METHODS: Forty-one healthy dogs, 8 dogs in an induced ITP model (3 control, 5 ITP), and 58 pITP dogs.
METHODS: Recombinant canine TPO (rcTPO) was purchased and its identity confirmed by mass spectrometry. Monoclonal antibodies were raised to rcTPO and used to configure a sandwich ELISA using streptavidin-biotin detection. Assay performance, coefficients of variability, and healthy dog plasma TPO reference interval (RI) were determined, followed by assay of ITP samples.
RESULTS: Assay dynamic range was 15 pg/mL (lower limit of detection) to 1000 pg/mL TPO, with limit of quantitation of 62 pg/mL. Plasma TPO RI was 0 to 158 pg/mL, with plasma TPO <62 pg/mL for 35/41 healthy dogs. All dogs with induced ITP developed marked increases in plasma TPO concentration. Peak values ranged from 515 to >6000 pg/mL. In contrast, only 2/58 pITP dogs had TPO values above RI.
CONCLUSIONS: Plasma TPO concentration is paradoxically low at diagnosis for most dogs with pITP. This finding suggests that ineffective thrombopoiesis contributes to thrombocytopenia in pITP dogs and supports evaluating TPO receptor agonist treatment as used for pITP in humans. The TPO assay provides a new tool to study thrombopoiesis in pITP and other thrombocytopenic syndromes in dogs.

The virtual control group (VCG) concept provides a potential opportunity to reduce animal use in drug development by replacing concurrent control groups (CCGs) in nonclinical toxicity studies. This work investigated the feasibility and reliability of using VCGs in place of CCGs. A historical control database (HCD), constructed from Genentech Inc. rat toxicity study data, was reviewed to understand trends and sources of variability in control animals over time, and to identify data curation requirements for assembling VCGs, e.g. alignment of units of measurement. Several endpoints were investigated and stratified against different study design parameters. Sex, route of administration, fasting status, and body weight at study initiation were among the parameters that were indicated as key matching criteria. With a high-level understanding of potential sources of variability, a retrospective proof-of-concept (POC) study was designed, evaluating a historical rat pilot toxicity study for test article-related changes. A masked interpretation of the study was conducted using its CCG, and two unique VCGs that were constructed from individual animal data pulled from our HCD. While the results of the microscopic pathology assessment and most endpoints were similar across the different control groups, the POC revealed the risk of using VCGs to interpret subtle test article-related changes in clinical pathology parameters. Within the context of our POC, it appears the use of a VCG is not completely equivalent to the CCG especially with clinical pathology parameters. Additional work is needed to understand the potential utility, and thus, viability of VCGs in other contexts.
This study explored the use of virtual control groups (VCGs) as a potential method to reduce the number of living control animals in drug development. The process involves replacing concurrent control groups with historical animal data in nonclinical toxicity studies. Several parameters were identified as crucial factors that must be aligned before the construction of VCGs. The VCG concept was tested using a historical rat toxicity study, comparing results against the conventional control group as well as two unique VCGs. Although results were similar in most cases, potential risks in interpreting subtle changes in clinical pathology parameters were identified. Further work is needed to fully elucidate VCGs’ potential, and whether it is a viable alternative to current methods. The significance of this work lies in the possibility of reducing the number of animals used in testing, in support of the 3Rs (replace, reduce, and refine).

Dysphagia is a common gastrointestinal complaint in the pediatric population and should raise concern for oropharyngeal as well as esophageal disorders. We describe a 7-year old patient who was admitted to the hospital for sudden onset dysphagia, abdominal pain, and decreased oral intake. Extensive evaluations including endoscopy eventually revealed herpes simplex esophagitis as well as eosinophilic esophagitis. Herpes simplex esophagitis is a rare condition in the immunocompetent population and is typically self-resolving. Eosinophilic esophagitis is a chronic, inflammatory condition characterized by esophageal eosinophilia and signs of esophageal dysfunction. The concurrent presentation of both conditions in the pediatric population has rarely been described.

BACKGROUND: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and clinically aggressive hematologic malignancy originating from the precursors of plasmacytoid dendritic cells. BPDCN often involves the skin, lymph nodes, and bone marrow, with rapid clinical progression and a poor prognosis. The BPDCN diagnosis is mainly based on the immunophenotype.
METHODS: In this paper, we retrospectively analyzed 2 cases of BPDCN. Both patients were elderly males. The lesions manifested as skin masses. Morphological manifestations included diffuse and dense tumor cell infiltration of the dermis and subcutaneous tissues. Immunohistochemistry staining showed that cluster of differentiation CD4, CD56, CD43, and CD123 were positive.
CONCLUSIONS: In this paper, we retrospectively analyzed 2 cases of BPDCN. Both patients were elderly males. The lesions manifested as skin masses. Morphological manifestations included diffuse and dense tumor cell infiltration of the dermis and subcutaneous tissues. Immunohistochemistry staining showed that cluster of differentiation CD4, CD56, CD43, and CD123 were positive.

Previous hematologic and serum biochemistry reference interval (RI) values have been established for donkeys in various geographic regions, life-stages, or for specific donkey breeds. The last extensive investigation establishing RIs for adult donkeys in the United States (U.S.) was published over three decades ago. We aimed to establish updated robust RIs using a reference population of apparently healthy adult donkeys from across the U.S. Standard sized (n = 102), miniature (n = 17), and mammoth (n = 1) donkeys from four different states were enrolled, with 20% of the study population including donkeys captured directly from the wild in Death Valley National Park, CA. RIs were established in accordance with the American Society for Veterinary Clinical Pathology and Clinical Laboratory Standards Institute guidelines. The findings will assist practitioners with the interpretation of their complete blood count and biochemistry panel results in U.S. donkeys. This study also highlights a comparison of results for some important analytes in U.S. donkeys compared to U.S. horses and previously established donkey RIs.

OBJECTIVE: The objective of this study was to provide orientation values for fructosamine in adult llamas and to characterize relationships with other laboratory and clinical parameters.
METHODS: Data from 22 healthy adult llamas of both sexes.
METHODS: A retrospective study was conducted with the findings of a veterinary herd visit from August 2022. Fructosamine measured from plasma samples was characterized, and its relationships with clinical and laboratory diagnostic data was analyzed using descriptive statistics and correlation analysis.
RESULTS: Fructosamine was 311 ± 34 µmol/L (mean ± SD), with a range of 254.8 to 409.2 µmol/L. Males showed significantly higher plasma fructosamine levels than females (P < .05). Plasma fructosamine revealed significant positive correlations with glucose, total protein, and albumin and also with PCV, hemoglobin, calcium, sodium, and selenium. Female llamas revealed further positive correlations with body condition scoring.
CONCLUSIONS: The results of this study can be used as orientation values for fructosamine in llamas. Fructosamine is used to distinguish acute hyperglycemia caused by stress from chronic hyperglycemia in other species, which might be caused by disorders of the glucose metabolism.

Sickle cell disease (SCD) is an autosomal recessive genetic disorder characterized by the abnormal formation of sickle hemoglobin (HbS). Under conditions of deoxygenation, HbS undergoes polymerization, resulting in microvascular occlusion, tissue hypoxia, and infarction. The elevated mortality rate associated with SCD is primarily attributed to complications such as sepsis, acute chest syndrome, stroke, acute multiorgan failure, and pulmonary hypertension. Despite advancements in awareness and treatments, preventing mortality in young individuals with SCD remains a formidable challenge. In an effort to shed light on these challenges, we present a case of unexpected death associated with SCD to emphasize the pressing need for continued research and intervention strategies to improve patient outcomes.

Renal disease is often identified as a cause of morbidity and mortality in avian patients. However, currently, early antemortem detection of renal disease in avian patients is difficult. Anatomical and physiological differences between mammals and birds mean the use of commonly employed diagnostic testing (ie, measurement of blood urea nitrogen [BUN] and serum creatinine, urinalysis, and ultrasonography) are either nondiagnostic or difficult to achieve. Symmetric dimethylarginine (SDMA) is considered a more sensitive marker for renal disease in humans, dogs, and cats. However, SDMA has not yet been assessed for diagnostic use in any psittacine species. In this study, we establish reference ranges for SDMA in both Hispaniolan Amazon parrots (Amazona ventralis, HAP) and Quaker parrots (Myiopsitta monachus, QP). Blood was collected from 23 Amazon parrots and 32 Quaker parrots maintained in research facilities. Measurement of SDMA through a commercially available immunoassay (IA-SDMA) as well as creatinine, BUN, uric acid, phosphorus, calcium, sodium, potassium, and chloride were determined through IDEXX Laboratories. Plasma SDMA concentrations ranged from 6 to 15 µg/dL and 3 to 15 µg/dL for the HAP and QP, respectively. Sex was a confounding factor for the QP population, but sex did not have a significant effect on SDMA for the HAP population. No significant correlations were identified between SDMA concentrations and other parameters in either psittacine species. Our results show proof of concept for the IA-SDMA and provide reference intervals for SDMA in HAP and QP. Further investigation is required to determine the validity of this assay and the predictive power of SDMA in the detection of renal impairment for parrots and other common companion birds.

Fibroblast growth factor (FGF)-23 is a phosphaturic hormone. An association between increasing FGF-23 levels and progression of chronic kidney disease (CKD) was documented in cats, dogs, and humans. The information regarding reference intervals (RIs) of FGF-23 in cats is limited. We aimed to establish RIs in a large cohort of clinically healthy cats and to investigate correlations with sex and age. A total of 118 cats with unremarkable complete blood count and serum chemistry profile were included. Clinically sick cats, cats with concurrent diseases, suspicion of CKD, or receiving renal diets were excluded. FGF-23 concentrations were measured with the FGF-23 ELISA Kit. RIs were calculated using the reference interval advisor software 2.1 (Microsoft Excel). FGF-23 concentrations were correlated with sex and age. The RI for FGF-23 concentrations spanned 85.8 to 387.0 pg/mL (90% confidence interval: lower limit 40.5 to 103.9 pg/mL, upper limit: 354.6 to 425.0 pg/mL). No significant relationships (r2 = 0.044) were detected with age (p = 0.081) or sex (p = 0.191). Other studies of the same diagnostic assay calculated RIs of 56 to 700 pg/mL in 79 cats and <336 pg/mL in 108 cats, and in concordance with the present study, did not detect any correlation with sex or age.

(1) Background: the erythrocyte sedimentation rate (ESR) has been reported to increase in some infectious or inflammatory diseases in dogs, but no information on the frequency of increases in a routine clinical setting exists. The aim of this study was to assess the frequency of an increased ESR in dogs and to investigate its possible association with hematologic changes; (2) Methods: A total of 295 EDTA blood samples were randomly selected from the routine caseload of the Veterinary Teaching Hospital. Samples were grouped in controls and in pathologic groups based on the clinical presentation. A routine hemogram was performed, then the ESR was measured using the instrument MINI-PET; (3) Results: compared with controls, the ESR was significantly higher in all the pathologic groups, except for the hematological disorders group. The highest ESR was found in samples from dogs with chronic kidney disease or inflammation, followed by those from dogs with mild chronic disorders, severe/acute diseases, tumors and urinary disorders. The ESR negatively correlated with hematocrit and positively with neutrophil counts. (4) Conclusions: The ESR increases more frequently in dogs with clinically evident inflammation or CKD, but also in several other conditions, likely as a consequence of anemia and acute phase response.