Martínez-Caro J, Agulla B, Benet A
… +1 more, Pastor J
Vet Clin Pathol
· 2025 Mar · PMID 39663591
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A 6-year-old, intact male English Bulldog presented for evaluation of weakness. Physical examination revealed mildly pale mucous membranes and ophthalmologic alterations. A complete blood cell count was performed on the...A 6-year-old, intact male English Bulldog presented for evaluation of weakness. Physical examination revealed mildly pale mucous membranes and ophthalmologic alterations. A complete blood cell count was performed on the Urit Smart V5 and the Sysmex XN-1000V, and showed several hematologic discrepancies between the analyzers. The Urit reported marked leukocytosis and thrombocytosis, and the Sysmex reported marked thrombocytosis on the impedance and optical RET channel but mild thrombocytopenia on the optical PLT-F channel. On the blood smear examination, there was an abundant proteinaceous material compatible with cryoglobulins. The red blood cell exhibited a notable degree of poikilocytosis. The number of leukocytes was found to be correlated with the Sysmex total white blood cell count, while the platelet count demonstrated a better correlation with the optical PLT-F channel from the Sysmex. Centrifugation of the blood in a capillary tube (at room temperature) identified a cryoglobulin precipitate. Additionally, the blood was reanalyzed soon after warming it to 37°C, which partially corrected most of the interferences. The serum protein electrophoresis demonstrated a marked hyperproteinemia with mild hypoalbuminemia and a marked hypergammaglobulinemia. On diagnostic imaging, a mild splenomegaly was noted. Cytology of the spleen showed Leishmania infantum infection, plasma cell hyperplasia, and extramedullary hematopoiesis. This is the first description of a dog infected with Leishmania. infantum with concurrent monoclonal hypergammaglobulinemia and cryoglobulinemia. We present a detailed description of the interference of cryoglobulin with the Urit Smart V5 and the Sysmex XN-1000V, along with the usefulness of Sysmex PLT-F in this condition.
Hayes JM, Hayes MR, Friedrichs KR
… +1 more, Simmons HA
Vet Clin Pathol
· 2025 Dec · PMID 39638966
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BACKGROUND: Manual blood smear review (MSR) to complement automated CBC results is a labor-intensive process. Efforts have been made to use criteria based on automated hematology analyzer data to identify samples warrant...BACKGROUND: Manual blood smear review (MSR) to complement automated CBC results is a labor-intensive process. Efforts have been made to use criteria based on automated hematology analyzer data to identify samples warranting MSR. These efforts have coincided with the emergence of modern data science and machine learning. OBJECTIVE: In this study, we aim to determine if machine learning can reduce manual smear review (MSR) rates while meeting or exceeding the performance of traditional MSR criteria. METHOD: 9938 automated CBCs with paired MSRs were performed on samples from rhesus and cynomolgus macaques. The definition of a positive (abnormal) smear was determined. Two expert-derived MSR criteria were created: criteria adapted from published, standardized human laboratory criteria (Adapted International Consensus Guidelines[aICG]) and internally generated criteria (Center Consensus Guidelines [CCG]). An ensemble machine learning model was trained on an independent subset of the data to optimize the balanced accuracy of classification, a combined measure of sensitivity and specificity. The resulting machine learning model and the two expert-derived MSR criteria were applied to a test dataset, and their performance compared. RESULTS: aICG criteria demonstrated high sensitivity (80.8%) and MSR rate (74.2%) while CCG criteria demonstrated lower sensitivity (57.1%) and MSR rate (36.1%). The machine learning model integrated with CCG criteria had a superior combination of both sensitivity (76.8%) and MSR rate (45.1%) achieving a false negative rate of 1.6%. CONCLUSION: Machine learning in combination with expert-derived criteria can optimize the selection of samples for MSR thus decreasing MSR rates and labor efforts required for CBC performance.
Pacholec C, Flatland B, Xie H
… +1 more, Zimmerman K
Vet Clin Pathol
· 2025 Dec · PMID 39638756
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Artificial intelligence (AI) has transformative potential in veterinary pathology in tasks ranging from cell enumeration and cancer detection to prognosis forecasting, virtual staining techniques, and individually tailor...Artificial intelligence (AI) has transformative potential in veterinary pathology in tasks ranging from cell enumeration and cancer detection to prognosis forecasting, virtual staining techniques, and individually tailored treatment plans. Preclinical testing and validation of AI systems (AIS) are critical to ensure diagnostic safety, efficacy, and dependability. In this two-part series, challenges such as the AI chasm (ie, the discrepancy between the AIS model performance in research settings and real-world applications) and ethical considerations (data privacy, algorithmic bias) are reviewed and underscore the importance of tailored quality assurance measures that address the nuances of AI in veterinary pathology. This review advocates for a multidisciplinary approach to AI development and implementation, focusing on image-based tasks, highlighting the necessity for collaboration across veterinarians, computer scientists, and ethicists to successfully navigate the complex landscape of using AI in veterinary medicine. It calls for a concerted effort to bridge the AI chasm by addressing technical, ethical, and regulatory challenges, facilitating AI integration into veterinary pathology. The future of veterinary pathology must balance harnessing AI's potential while intentionally mitigating its risks, ensuring the welfare of animals and the integrity of the veterinary profession are safeguarded. Part I of this review focuses on considerations for model development, and Part II focuses on external validation of AI.
Vet Clin Pathol
· 2025 Mar · PMID 39617948
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BACKGROUND: Basophils are the rarest blood leukocyte in most healthy domestic mammals and the clinical significance of basophilia is poorly understood. OBJECTIVES: To empirically determine magnitude thresholds for basoph...BACKGROUND: Basophils are the rarest blood leukocyte in most healthy domestic mammals and the clinical significance of basophilia is poorly understood. OBJECTIVES: To empirically determine magnitude thresholds for basophilia, identify its hematologic correlates, and identify associations between breeds, specific diseases, disease categories, organ systems, and basophilia in dogs, cats, and horses. METHODS: CBCs and clinical information from dogs, cats, and horses were collected from the University of California-Davis School of Veterinary Medicine between 2000 and 2020. Relationships between basophil concentration and other CBC parameters were evaluated by computing Pearson's correlation (r). Magnitude thresholds for basophilia (ie, mild, moderate, severe) were determined by evaluating the distribution of basophil counts for each species. For severe cases of basophilia, the clinical diagnoses were categorized by the organ system affected and the underlying pathomechanism. Basophilia groups were compared to a time-matched, randomly selected control group, and chi-square analyses were performed to evaluate associations with disease. RESULTS: A total of 143 841 (dog), 32 576 (cat), and 44 887 (horse) CBCs were collected. For all three species, basophilia was over-represented in some breeds. Basophilia was associated with respiratory disease in both dogs and cats. In dogs, lymphoma and mast cell neoplasia were associated with basophilia. In horses, an increased incidence of basophilia was not associated with any disease category or organ system. CONCLUSIONS: This is the largest study evaluating the hematologic correlations and disease associations with basophilia in dogs, cats, and horses. While basophilia was reported alongside many diseases, certain associations may aid clinicians in narrowing down underlying causes.
Jornet-Rius O, Chornarm N, Skeldon N
… +4 more, McGrew A, Lappin M, Solano-Gallego L, Moore AR
Vet Clin Pathol
· 2024 Dec · PMID 39528734
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BACKGROUND: Canine vector-borne diseases (VBDs) induce non-specific dysproteinemias, detectable by serum protein electrophoresis (SPE). VBDs have been reported to induce a monoclonal gammopathy pattern. Monoclonal gammop...BACKGROUND: Canine vector-borne diseases (VBDs) induce non-specific dysproteinemias, detectable by serum protein electrophoresis (SPE). VBDs have been reported to induce a monoclonal gammopathy pattern. Monoclonal gammopathies are commonly the result of paraprotein (M-protein) produced by an immunoglobulin-secreting neoplasm. OBJECTIVES: The aims of this study were to characterize and compare SPE and immunofixation (IF) changes, evaluate the performance of previously identified SPE and IF interpretative criteria, and identify M-proteins in a cohort of dogs seropositive for a VBD and with an unknown history for an immunoglobulin-secreting neoplasm. METHODS: A total of 143 serum samples from dogs that tested seropositive for different vector-borne pathogens were assessed by SPE. Cases with abnormal globulin fractions were further characterized by IF. Protein fraction and IF labeling results were evaluated using Kruskal-Wallis with Dunn's multiple comparisons and principal component analysis (PCA). RESULTS: IF was performed in 112 VBD-seropositive samples with dysproteinemia evaluated by SPE. Most (84/112, 75%) had a polyclonal expansion. Only two dogs had findings suggestive of an M-protein when considering both SPE and immunofixation. PCA clustered E.canis/A.phagocytophilum and B.gibsoni/CM.haematoparvum groups with relatively more γ-globulins than albumin and α-globulins, and the B.gibsoni/CM.haematoparvum group with more prominent IgA and IgM labeling than IgG labeling. Additionally, D.immitis clustered with more prominent β-globulins than γ-globulins and more IgG4 than IgG-FC. CONCLUSIONS: The previously derived interpretative criteria suggested an M-protein in very few VBD-seropositive dogs. PCA identified SPE and immunofixation pattern differences between dogs seropositive for different infectious agents.
Zoia A, Morini L, Mazzei A
… +4 more, Talavera Lopez J, Pardo-Marín L, Cerón JJ, Tecles F
Vet Clin Pathol
· 2024 Dec · PMID 39434423
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BACKGROUND: In dogs, simplified Light's criteria can discriminate transudates from exudates. Other tests used in human medicine are pleural effusion cholesterol (CHOL) and butyrylcholinesterase [BChE], the pleural effusi...BACKGROUND: In dogs, simplified Light's criteria can discriminate transudates from exudates. Other tests used in human medicine are pleural effusion cholesterol (CHOL) and butyrylcholinesterase [BChE], the pleural effusion/serum ratio of these analytes (CHOL and BChE), and the serum albumin minus pleural effusion albumin gradient (SEAG). OBJECTIVES: We aimed to assess the diagnostic accuracies of different biomarkers in dogs with pleural effusion in differentiating exudates from transudates. Secondarily, we evaluated the potential diagnostic utility of pleural effusion acute phase proteins, amylase, and adenosine deaminase in discriminating causes of exudative effusions. METHODS: Cross-sectional study including 68 client-owned dogs with pleural effusion. RESULTS: There were 48 exudates (10 septic, 16 neoplastic, 9 hemorrhagic, and 13 classified as other exudates) and 20 transudates. All the variables analyzed, except SEAG, were significantly different between exudates and transudates. Using the cut-off values adopted in human literature, accuracies for CHOL, CHOL, BChE, and BChE were between 82.35% and 85.29%; all values were significantly lower compared with the previously published simplified Light's criteria accuracy (i.e., 98%, p < .001 for all comparisons). We found the accuracy of the simplified Light's criteria to be similar to what has been previously reported (95.59%, p = .238). Paraoxonase-1 (PON-1) activity and the pleural effusion/serum paraoxonase-1 ratio (PON-1) were significantly lower in exudative neoplastic effusions than in exudative hemorrhagic (p = .004 and p = .001) and septic (p = .004 and p < .001) effusions. CONCLUSION: Simplified Light's criteria were the best method for discriminating transudates from exudates, and a low PON-1 activity and PON-1 in exudative effusions may suggest an underlying neoplasia.
Vet Clin Pathol
· 2024 Oct · PMID 39432048
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Urinary extracellular vesicles (UEVs) are membranous particles that carry renal tubular transporter proteins. Here, we evaluate whether selected renal tubular transporter proteins can be detected in UEVs isolated from sm...Urinary extracellular vesicles (UEVs) are membranous particles that carry renal tubular transporter proteins. Here, we evaluate whether selected renal tubular transporter proteins can be detected in UEVs isolated from small volume (1-5 mL) canine urine samples of healthy dogs and canine patients with elevated circulating parathyroid hormone (PTH)/PTH-related peptide (PTHrp) concentrations, hypercortisolism, and primary hypoadrenocorticism using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The total creatinine content of each urine sample was calculated from urine volume and creatinine concentration. UEVs were isolated by size exclusion chromatography prior to quantification by nanoparticle tracking analysis and proteomic analysis by LC-MS/MS. Group comparisons were made using non-parametric statistics. Aquaporin-2 (AQP2) and the renal sodium/phosphate co-transporter (NPT2A) were detected in UEVs isolated from small volume samples of almost all healthy dogs but were not detected in most dogs with elevated circulating PTH/PTH related peptide (PTHrp) concentrations, hypercortisolism and primary hypoadrenocorticism. Total creatinine content of the urine sample was strongly positively correlated with the number of UEVs (r = .84, P < .001); thus, total creatinine was used as a surrogate marker of UEV number. In healthy dogs, AQP2 and NPT2A were both detected in samples containing at least 1.7 × 10 UEVs or 24 μmol creatinine, however in non-healthy dogs, AQP2 and NPT2A were not detected in most samples containing up to 6.3 × 10 UEVs or 32 μmol creatinine.
Vet Clin Pathol
· 2024 Dec · PMID 39432023
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BACKGROUND: Haptoglobin (Hp) is an emerging diagnostic marker in cattle, and knowledge of suitable sample types and measurement methods is important. OBJECTIVES: The aims of this study were to compare the results of a co...BACKGROUND: Haptoglobin (Hp) is an emerging diagnostic marker in cattle, and knowledge of suitable sample types and measurement methods is important. OBJECTIVES: The aims of this study were to compare the results of a colorimetric assay (CA) and an ELISA for bovine Hp using serum, EDTA plasma, and lithium-heparinized (LH) plasma, respectively, and to assess the diagnostic potential for puerperal metritis. METHODS: In experiment 1, Hp was measured in pooled aliquots of serum (n = 10), EDTA plasma (n = 10), and LH plasma (n = 10) of 100 healthy fresh lactating dairy cows from 10 farms using both the CA and the ELISA. In experiment 2, five healthy and five cows with acute puerperal metritis were sampled, and Hp was determined using both assays for all three sample types. In experiment 3, aliquots of serum and LH plasma from cows in different lactation stages were transferred into plain, EDTA-coated, and LH-coated tubes and mixed before colorimetric analyses. Distilled water was also placed into each tube type and treated similarly. RESULTS: Plasma samples measured with the CA showed on average 2.3 (EDTA) and 2.5 (LH) times higher Hp concentrations compared with serum, whereas no differences were seen with the ELISA results between sample types. Based on a clinical cut-off value, both methods differentiated sick from healthy cows. Haptoglobin measurements with the ELISA were less precise compared with CA measurements due to high dilutions. No influence of the anticoagulants on the CA was observed. CONCLUSIONS: Due to measurement discrepancies between serum and plasma, CAs for bovine Hp based on peroxidase activity should be performed with serum, or specific reference ranges for plasma samples should be established. In this study, CA results obtained with LH plasma were more precise than results obtained with EDTA plasma. Both the CA and the ELISA are suitable diagnostic tools for the diagnosis of puerperal metritis, but CA measurements were more precise in this study.
Perez-Montero B, Fermin-Rodriguez ML, Portero-Fuentes M
… +6 more, Sarquis J, Caceres S, Del Portal JCI, de Juan L, Miro G, Cruz-Lopez F
Vet Clin Pathol
· 2024 Dec · PMID 39396933
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BACKGROUND: Total antioxidant status (TAS) is one of the most widely used oxidative stress biomarkers, but the lack of canine RI and the influence of analytical factors hinder its application in clinical practice. OBJECT...BACKGROUND: Total antioxidant status (TAS) is one of the most widely used oxidative stress biomarkers, but the lack of canine RI and the influence of analytical factors hinder its application in clinical practice. OBJECTIVES: The aims of this study were to establish canine assay-specific RI for TAS and evaluate the sources of biological variation and the association between TAS and multiple hematologic and biochemical variables. METHODS: Blood samples from 190 clinically healthy dogs were collected, encompassing pet dogs (82), police dogs (56), and shelter dogs (52). After hematologic and biochemical analysis, serum TAS was determined by means of a commercial 2,2'-azinobis (3-ethylbenzthiazolin-6-sulfonic acid) (ABTS) test. The American Society for Veterinary Clinical Pathology guidelines were followed to establish the RI, employing nonparametric methods. Univariate analysis and multivariate analysis were conducted to assess the influence of biological and analytical variables, yielding a final regression model. RESULTS: The final reference population comprised 143 dogs, for which the RI was established (1.41-2.27 mmol/L). Partitioning was applied to the three study groups. The regression model revealed that police dogs had significantly higher TAS values than pet dogs. Furthermore, significant associations between four biochemical variables (albumin, globulins, cholesterol, and aspartate aminotransferase) and serum TAS were found. CONCLUSIONS: This is the first study to establish RI for serum TAS in a large and heterogeneous canine population and provide data on its relationship with analytical variables. These findings could potentially improve the interpretation of TAS in clinical environments.
Marconato L, Sabattini S, Zambelli D
… +7 more, Ferrari MG, Aresu L, Renzi A, Ferrari A, Cunto M, Maga I, Ballotta G
Vet Clin Pathol
· 2024 Dec · PMID 39384718
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Hematopoietic neoplasms are common in dogs; however, their association with pregnancy has not been previously reported in veterinary medicine. This rare occurrence presents a variety of diagnostic, therapeutic, prognosti...Hematopoietic neoplasms are common in dogs; however, their association with pregnancy has not been previously reported in veterinary medicine. This rare occurrence presents a variety of diagnostic, therapeutic, prognostic, and ethical challenges. We report a case of a 3-year-old pregnant Bernese Mountain Dog diagnosed with multicentric aggressive unclassified hematopoietic cancer associated with paraneoplastic hypercalcemia during pregnancy. The dog died 7 days after diagnosis, and at Day 36 of pregnancy before any treatment decision could be made. Post-mortem evaluation, including histology, immunohistochemistry, and clonality analysis, led to the diagnosis of an unclassified hematopoietic cancer affecting the uterus and placenta, with no evidence of fetal involvement. The placenta likely acted as a barrier, preventing neoplastic involvement of the fetuses. Alternatively, the pregnancy might have been too early for the hematopoietic neoplasm to affect the labyrinth zone of the placenta and the fetuses. The dramatic disease progression could be explained by compromised cell-mediated immunity during pregnancy. This immunodeficient state is induced by embryonic, maternal, and hormonal factors, which suppress the response to mitogens to prevent rejection of the placenta and the conceptuses. Thus, pregnant dogs might exhibit increased vulnerability to cancer and infectious diseases that rely on cell-mediated immunity for host defense.
Harris RA, Nolan J, Ammons D
… +3 more, Beeson S, Thamm D, Avery A
Vet Clin Pathol
· 2025 Dec · PMID 39367609
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Acute myeloid leukemia (AML) poses significant challenges in veterinary medicine, with limited treatment options and poor survival rates. While substantial progress has been made in characterizing human AML, translating...Acute myeloid leukemia (AML) poses significant challenges in veterinary medicine, with limited treatment options and poor survival rates. While substantial progress has been made in characterizing human AML, translating these advancements to veterinary practice has been hindered by limited molecular understanding and diagnostic tools. The case study presented illustrates the application of whole genome sequencing in diagnosing AML in a dog, showcasing its potential in veterinary oncology. Our approach facilitated comprehensive genomic analysis, identifying mutations in genes that may be associated with AML pathogenesis in dogs, such as KRAS, IKZF1, and RUNX1. However, without supportive evidence of its clinical utility (eg, association with response to treatment or prognosis), the information is limited to exploration. This article reviews the comparative features of canine AML with human AML and discusses strategies to shrink the knowledge gap between human and veterinary medicine with cost-effective next-generation sequencing (NGS) techniques. By utilizing these approaches, the unique and shared molecular features with human AML can be identified, aiding in molecular classification and therapeutic development for both species. Despite the promise of NGS, challenges exist in implementing it into routine veterinary diagnostics. Cost considerations, turnaround times, and the need for robust bioinformatics pipelines and quality control measures must be addressed. Most importantly, analytical and clinical validation processes are essential to ensure the reliability and clinical utility of NGS-based assays. Overall, integrating NGS technologies into veterinary oncology holds great potential for advancing our understanding of AML and improving disease stratification, in hopes of improving clinical outcomes.
A feline cutaneous melanocytic tumor in a 1-year-old cat is reported. The cytologic, histologic, and immunohistochemical characteristics of the pediatric feline cutaneous melanocytoma are included. A solitary, black-colo...A feline cutaneous melanocytic tumor in a 1-year-old cat is reported. The cytologic, histologic, and immunohistochemical characteristics of the pediatric feline cutaneous melanocytoma are included. A solitary, black-colored nodule on the head was histologically diagnosed as the epithelioid type of melanocytoma. Immunohistochemically, the neoplastic melanocytes demonstrated immunoreactivity to the S100 and MelanA antibodies but not to the PNL2 antibody. Despite high mitotic counts (17/10HPFs) and a Ki67 index (33%) suggesting malignant melanoma, the patient exhibited a favorable 5-month outcome. The mitotic activity of the neoplastic cells may not provide a reliable prediction for feline melanocytic tumors.