Bone marrow, blood, and clinical findings in dogs treated with phenobarbital.

BACKGROUND: Cytopenias have been reported in dogs treated with phenobarbital, but detailed descriptions of bone marrow findings and response to treatment are lacking. OBJECTIVES: We aimed to characterize the hematologic findings and clinical outcomes of dogs that had been receiving phenobarbital at the time of marrow evaluation. METHODS: Archived bone marrow slides and clinicopathologic data were reviewed in dogs undergoing marrow evaluation for any hematologic problems that developed while receiving phenobarbital (2008-2020). Dogs were excluded if marrow samples lacked diagnostic value, phenobarbital was withdrawn >1 day before marrow collection, a same-day complete blood count (CBC) was lacking, or dogs had concurrent illness or therapy known to cause cytopenias. RESULTS: Thirteen dogs met inclusion criteria: eight pancytopenic, three anemic/thrombocytopenic, one neutropenic/thrombocytopenic, and one nearly neutropenic. Neutropenia was marked (<700/µL) in eight dogs; all neutrophil concentrations were low or low-normal. Of the 11 anemic dogs (Hct = 12%-42%, median = 29%), three had mild reticulocytosis (eight were tested). One dog had erythroid dysplasia in blood and marrow. All nine neutropenic dogs had evidence of ineffective neutropoiesis: neutrophilic hyperplasia with left shift (9) ± neutrophagocytosis (5). Eight of the 11 anemic dogs had evidence of ineffective erythropoiesis: erythroid hyperplasia (7), left shift (3), and/or rubriphagocytosis (6). No thrombocytopenic dog had megakaryocytic hypoplasia; seven dogs had megakaryocytic hyperplasia. One anemic/thrombocytopenic dog had marked collagen myelofibrosis. The noncytopenic dog had equivocal myeloid hypoplasia with neutrophagocytosis. Median maximal responses and resolution times for neutropenia (n = 6) were 14 days. CONCLUSIONS: Phenobarbital-induced cytopenias should be considered in dogs with multilineage ineffective hematopoiesis, particularly when neutropenia and myeloid hyperplasia are present. However, findings in dogs with immune-mediated neutropenia or precursor-targeted immune-mediated anemia might be indistinguishable.

Clinical features of precursor-targeted immune-mediated anemia in dogs: 66 cases (2004-2013).

OBJECTIVE: To characterize the clinical features of dogs with precursor-targeted immune-mediated anemia (PIMA). ANIMALS: 66 dogs with PIMA. PROCEDURES: Electronic record databases of a teaching hospital were searched to identify dogs with a diagnosis of nonregenerative anemia between 2004 and 2013. Inclusion criteria included persistent nonregenerative anemia (Hct ≤ 30% and reticulocyte count < 76,000 reticulocytes/µL), cytologic findings supportive of ineffective bone marrow erythropoiesis, and absence of underlying disease. Information regarding clinical signs, clinicopathologic findings, treatment, and outcome was extracted from records of eligible dogs. A regenerative response was defined as a reticulocyte count > 76,000 reticulocytes/µL or sustained increase in Hct of > 5%. Remission was defined as a stable Hct ≥ 35%. RESULTS: The median Hct was 13%, and reticulocyte count was 17,900 reticulocytes/µL. Rubriphagocytosis was identified in bone marrow aspirate samples from 61 of 66 dogs. Collagen myelofibrosis was detected in bone marrow biopsy specimens obtained from 31 of 63 dogs. Immune-mediated targeting of mature erythrocytes was uncommon. All dogs received immunosuppressive therapy. Fifty-five dogs developed a regenerative response at a median of 29 days, and 40 of those dogs went into remission at a median of 59 days after PIMA diagnosis. Thromboembolic events were confirmed for 9 dogs and were associated with a decreased survival time. Median survival time was 913 days for all dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that most dogs with PIMA responded to prolonged immunosuppressive therapy. Studies to determine optimal immunosuppressive and thromboprophylactic protocols for dogs with PIMA are warranted.

Clinical features of canine pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis.

BACKGROUND: Histologic features of pulmonary veno-occlusive disease (PVOD) and pulmonary capillary hemangiomatosis (PCH) have been described in dogs but without a thorough clinical description. OBJECTIVES: To report the clinical features, diagnostics, treatment, and outcome of dogs with histologic evidence of PVOD and PCH. ANIMALS: Fifteen pet dogs meeting histopathologic criteria of PVOD (occlusive remodeling of small-sized to medium-sized pulmonary veins) or PCH (alveolar capillary proliferation and congestion), or both. METHODS: Medical records of dogs with PVOD and PCH identified based on histopathologic features between 2003 and 2017 were retrospectively reviewed. RESULTS: Fifteen dogs met inclusion criteria of a histologic diagnosis of PVOD or PCH or both. Dogs were older (median 11 years) with no apparent breed or sex predisposition. Dogs presented with acute clinical signs (median 3 days), usually respiratory distress. Thoracic radiography (available in 10 dogs) revealed right cardiomegaly and patchy or diffuse interstitial to alveolar patterns, with 9 dogs having a normal left cardiac silhouette. In 5 dogs tested, pulmonary arterial hypertension (PAH) was documented. In all 3 dogs, thoracic computed tomography scans showed pulmonary arterial enlargement and perivascular diffuse nodular ground-glass opacities. Ten of 15 dogs died within 1 day; median survival was 3 days. CONCLUSIONS AND CLINICAL IMPORTANCE: In dogs with PAH, the inability to document left-sided congestive heart failure and failure to identify another cause of signs of respiratory disease should increase suspicion for PVOD and PCH. With increased awareness of PVOD and PCH by clinicians and pathologists, dogs with compatible clinicopathologic features should be evaluated for these pulmonary vascular disorders.

Analytic characterization of flow cytometric assays for detection of immunoglobulin G on canine erythroid cells, including detection of dog erythrocyte antigen 1 on erythroid precursors.

OBJECTIVE To develop and characterize flow cytometric assays for detecting IgG bound to canine erythrocytes and bone marrow erythroid precursors. SAMPLE Blood samples from 20 healthy and 61 sick dogs with (n = 33) or without (28) immune-mediated hemolytic anemia (IMHA) and bone marrow samples from 14 healthy dogs. PROCEDURES A flow cytometric assay for measurement of IgG on RBCs was developed, and appropriate positive control cells were generated. Analytic and diagnostic performance were characterized. The RBC IgG assay was then combined with density-gradient fractionation of aspirated bone marrow cells and a 2-color process to yield an assay for detecting IgG on nucleated RBCs (nRBCs). Cell sorting and cytologic examination confirmed target cell populations, and anti-dog erythrocyte antigen 1 (DEA1) blood-typing serum was used to generate IgG-positive nRBCs. RESULTS Within- and between-run coefficients of variation for the RBC IgG assay were 0.1% to 13.9%, and > 90% of spiked IgG-positive RBCs were detected. Diagnostic sensitivity and specificity of the assay for detection of IMHA were 88% and 93%, respectively. Cytologic findings for sorted bone marrow fractions rich in early-, mid-, and late-stage nRBCs from 3 healthy dogs indicated 89% to 98% nRBC purity. After IgG coating with anti-DEA1 blood-typing serum, IgG was detected on nRBCs from DEA1-positive, but not DEA1-negative, healthy dogs. CONCLUSIONS AND CLINICAL RELEVANCE The developed RBC IgG assay had favorable analytic and diagnostic performance for detection of IMHA in dogs and was successfully adapted to detect IgG on canine nRBCs of various maturation stages. The findings supported the presence of DEA1 on canine nRBCs.

Histologic and cytologic bone marrow findings in dogs with suspected precursor-targeted immune-mediated anemia and associated phagocytosis of erythroid precursors.

BACKGROUND: Precursor-targeted immune-mediated anemia (PIMA) has been suspected in dogs with nonregenerative anemia and bone marrow findings varying from erythroid hyperplasia to pure red cell aplasia. Phagocytosis of erythroid precursors/rubriphagocytosis (RP) reported in some affected dogs suggests a destructive component to the pathogenesis of PIMA. OBJECTIVES: The purpose of the study was to characterize laboratory and clinical findings in dogs with suspected PIMA and RP, with emphasis on cytologic and histologic bone marrow findings. METHODS: Dogs with PIMA and RP were identified by review of paired bone marrow aspirate and core biopsy slides collected over a 4-year period. Samples were systematically assessed and characterized along with other pertinent laboratory data and clinical findings. RESULTS: Twenty-five dogs met criteria for PIMA and had RP that was relatively stage-selective. Erythropoiesis was expanded to the stage of erythroid precursors undergoing most prominent phagocytosis, yielding patterns characterized by a hypo-, normo-, or hypercellular erythroid lineage. A 4th pattern involved severe collagen myelofibrosis, and there was a spectrum of mild to severe collagen myelofibrosis overall. Evidence of immune-mediated hemolysis was rare. Immunosuppressive therapy was associated with remission in 77% of dogs treated for at least the median response time of 2 months. CONCLUSIONS: Bone marrow patterns in dogs fulfilling criteria for PIMA were aligned with stage-selective phagocytosis of erythroid precursors and the development of collagen myelofibrosis, common in dogs with PIMA. Recognition of these patterns and detection of RP facilitates diagnosis of PIMA, and slow response to immunosuppressive therapy warrants further investigation into its pathogenesis.

Effect of sorbitol, single, and multidose activated charcoal administration on carprofen absorption following experimental overdose in dogs.

OBJECTIVE: To compare the effectiveness of single dose activated charcoal, single dose activated charcoal with sorbitol, and multidose activated charcoal in reducing plasma carprofen concentrations following experimental overdose in dogs. DESIGN: Randomized, four period cross-over study. SETTING: University research setting. ANIMALS: Eight healthy Beagles. INTERVENTIONS: A 120 mg/kg of carprofen was administered orally to each dog followed by either (i) a single 2 g/kg activated charcoal administration 1 hour following carprofen ingestion (AC); (ii) 2 g/kg activated charcoal with 3.84 g/kg sorbitol 1 hour following carprofen ingestion (ACS); (iii) 2 g/kg activated charcoal 1 hour after carprofen ingestion and repeated every 6 hours for a total of 4 doses (MD); (iv) no treatment (control). MEASUREMENTS AND MAIN RESULTS: Plasma carprofen concentrations were obtained over a 36-hour period following carprofen ingestion for each protocol. Pharmacokinetic modeling was performed and time versus concentration, area under the curve, maximum plasma concentration, time to maximum concentration, and elimination half-life were calculated and compared among the groups using ANOVA followed by Tukey's multiple comparisons test. Activated charcoal, activated charcoal with sorbitol (ACS), and multiple-dose activated charcoal (MD) significantly reduced the area under the curve compared to the control group. AC and MD significantly reduced the maximum concentration when compared to the control group. MD significantly reduced elimination half-life when compared to ACS and the control group. There were no other significant differences among the treatment groups. CONCLUSIONS: Activated charcoal and ACS are as effective as MD in reducing serum carprofen concentrations following experimental overdose in dogs. Prospective studies are warranted to evaluate the effectiveness of AC, ACS, and MD in the clinical setting.

Evaluation of two point-of-care ethylene glycol tests for dogs.

OBJECTIVE: To evaluate 2 point-of-care ethylene glycol (EG) tests in dogs. DESIGN: Prospective, randomized, blinded laboratory evaluation. SETTING: University teaching hospital. ANIMALS: Ten healthy adult dogs. INTERVENTIONS: Jugular venipuncture and in vitro evaluation for detection of EG in canine blood. MEASUREMENTS: Whole blood samples were centrifuged and separated, and the plasma was divided into 30 aliquots. The aliquots were mixed with EG to provide EG concentrations ranging from 0 to 100 mg/dL. The EG concentration of each sample was confirmed using gas chromatography. For the VetSpec EG Qualitative Reagent Test Kit, 100 µL of each sample was added to test vials and compared with 20 and 50 mg/dL reference vials. For the Kacey EG Test Strips, 20 µL of each sample was added to the test circle and compared with the color chart provided by the manufacturer. For each test, samples were prepared in groups of 5 and presented in randomized order to 2 readers who were blinded to the presumed EG concentration. Samples were scored as negative, 20-50 mg/dL, or greater than 50 mg/dL. For each test, the sensitivity and specificity for detecting EG was calculated. Cohen's unweighted kappa coefficient was calculated to determine the degree of agreement between readers. MAIN RESULTS: For detecting EG, the Kacey EG Test Strips had excellent sensitivity and specificity (both 100%) and good agreement between readers. The VetSpec EG Qualitative Reagent Test Kit was less sensitive and specific (65% and 70% for the first reader, 95% and 40% for the second) with less agreement. CONCLUSIONS: Of the 2 systems evaluated, the Kacey EG Test Strips displayed greater accuracy and ease of use.

Comparative stability of canine and feline hemostatic proteins in freeze-thaw-cycled fresh frozen plasma.

OBJECTIVE: To evaluate the stability of canine and feline hemostatic proteins in freeze-thaw-cycled (FTC) fresh frozen plasma (FFP). DESIGN: Prospective study. SETTING: Veterinary Teaching Hospital. ANIMALS: Nine blood donor dogs and 10 blood donor cats. INTERVENTIONS: Whole blood was collected and separated into packed RBC and plasma units according to standard methods. Each unit of plasma was divided into 2 equal aliquots and frozen (-41 °C). One aliquot from each donor (FTC) was then thawed and then refrozen (-41 °C) until time of analysis. The second aliquot (nonfreeze-thaw-cycled; NFTC) remained frozen until time of analysis. The hemostatic proteins assessed included coagulation factors, anticoagulant factors (antithrombin and Protein C), and adhesive proteins (fibrinogen and von Willebrand Factor). The coagulant activities of factors II, VII, VIII, IX, X, XI, and XII were measured in modified one-stage activated partial thromboplastin time or prothrombin time assays. Antithrombin and Protein C activities were measured in chromogenic substrate assays. Clottable fibrinogen was measured via the Clauss method, and von Willebrand Factor concentration (vWF:Ag) was measured in an ELISA. A paired t-test was utilized to identify differences in factor activity or concentration between FTC FFP and NFTC FFP. MEASUREMENTS AND MAIN RESULTS: No clinically or statistically significant differences (all P>0.05) were identified between FTC FFP and NFTC FFP. CONCLUSIONS: Refreezing FFP within 1 hour of initial thawing appeared to have no deleterious effects on the hemostatic protein activity or content of that unit. Transfusion of FTC FFP is expected to provide the recipient with comparable replacement of hemostatic proteins as FFP that has remained frozen.

Continuous versus intermittent delivery of nutrition via nasoenteric feeding tubes in hospitalized canine and feline patients: 91 patients (2002-2007).

OBJECTIVE: To compare continuous to intermittent feeding at delivering prescribed nutrition in hospitalized canine and feline patients. DESIGN: Retrospective clinical study. SETTING: University teaching hospital. ANIMALS: Fifty-four cats and 37 dogs. MEASUREMENTS AND MAIN RESULTS: Twenty-four-hour periods of prescribed and delivered nutrition (kcal) were recorded, and the percentage of prescribed nutrition delivered (PPND) was calculated. If the patient received nasoenteric feeding for >1 day, then the average PPND per day was calculated. Frequency of gastrointestinal complications (vomiting, diarrhea, and regurgitation) was calculated per patient for each group. The PPND was not significantly different between patients fed continuously (99.0%) and patients fed intermittently (92.9%). Vomiting affected 29% of patients (26/91), diarrhea affected 26% of patients (24/91), and regurgitation affected 5% of patients (5/91). There was no significant difference in incidence of gastrointestinal complications between the patients fed continuously and the patients fed intermittently. There was a significantly higher incidence of diarrhea and regurgitation in dogs than in cats. CONCLUSIONS: PPND was not significantly different for continuous versus intermittent feeding via nasoenteric tubes. Frequencies of gastrointestinal complications were not significantly different between patients fed continuously and patients fed intermittently. Enterally fed dogs had a significantly higher frequency of regurgitation and diarrhea than enterally fed cats. Prospective studies are warranted to investigate causes for these potential inter-species differences.

Association between outcome and organ system dysfunction in dogs with sepsis: 114 cases (2003-2007).

OBJECTIVE: To determine whether multiple organ dysfunction syndrome (MODS) could be identified in dogs with sepsis secondary to gastrointestinal tract leakage, and whether the number of affected organ systems was significantly associated with mortality rate. DESIGN: Multicenter retrospective case series. ANIMALS: 114 dogs. PROCEDURES: Medical records for dogs treated surgically because of sepsis secondary to gastrointestinal tract leakage between 2003 and 2007 were reviewed. Sepsis was diagnosed on the basis of results of bacterial culture of peritoneal fluid, gross evidence of gastrointestinal tract leakage at surgery, or both. Renal dysfunction was defined as a > or = 0.5 mg/dL increase in serum creatinine concentration after surgery. Cardiovascular dysfunction was defined as hypotension requiring vasopressor treatment. Respiratory dysfunction was defined as a need for supplemental oxygen administration or mechanical ventilation. Hepatic dysfunction was defined as a serum bilirubin concentration > 0.5 mg/dL. Dysfunction of coagulation was defined as prolonged prothrombin time, prolonged partial thromboplastin time, or platelet count < or = 100,000/microL. RESULTS: 89 (78%) dogs had dysfunction of 1 or more organ systems, and 57 (50%) dogs had MODS. Mortality rate increased as the number of dysfunctional organ systems increased. Mortality rate was 70% (40/57) for dogs with MODS and 25% (14/57) for dogs without. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that MODS, defined as dysfunction of at least 2 organ systems, can be identified in dogs with sepsis and that organ system dysfunction increased the odds of death.

Left lateral and left middle liver lobe torsion in a Saint Bernard puppy.

A 5-month-old, male Saint Bernard was presented for acute collapse and abdominal discomfort. Significant findings were a cranial abdominal mass, hemorrhagic abdominal effusion, anemia, and disseminated intravascular coagulation. An exploratory surgery revealed torsion of both the left lateral and middle liver lobes, a condition that has not been previously described in the veterinary literature. Torsion of one or more hepatic lobes is a rare condition but should be considered as a differential diagnosis for acute abdomen syndrome in both young and mature dogs. Early diagnosis and prompt surgical intervention may be curative.

Reproductive emergencies.

The emergency clinician is frequently called on to manage problems relating to the female reproductive tract. Because owners sel-dom have the medical knowledge needed to differentiate normal from abnormal reproductive behaviors, they frequently look to the emergency veterinarian for guidance and information during and after parturition. For this reason, it is essential that the veterinarian have a good understanding of the normal reproductive cycle as well as the common emergencies that may occur. This article reviews the events surrounding normal parturition in the dog and cat and the reproductive emergencies seen most commonly in practice.

Massive transfusion in dogs: 15 cases (1997-2001).

OBJECTIVE: To determine clinical characteristics of dogs that received massive transfusion and identify the underlying diseases, complications, and outcomes. DESIGN: Retrospective study. ANIMALS: 15 dogs. PROCEDURE: Medical records of dogs receiving a massive blood transfusion were evaluated for transfusion volume, underlying disease process or injury, benefits and complications of transfusion, and outcome. A massive transfusion was defined as transfusion of a volume of blood products in excess of the patient's estimated blood volume (90 ml/kg [40 ml/lb]) in a 24-hour period or transfusion of a volume of blood products in excess of half the patient's estimated blood volume in a 3-hour period. RESULTS: Six dogs had intra-abdominal neoplasia resulting in hemoabdomen, 3 had suffered a traumatic incident resulting in hemoabdomen, and 6 had non-traumatic, non-neoplastic blood loss. Mean volumes of packed RBC and fresh-frozen plasma administered were 66.5 ml/kg (30 ml/lb) and 22.2 ml/kg (10 ml/lb), respectively. All dogs evaluated developed low ionized calcium concentrations and thrombocytopenia. Transfusion reactions were recognized in 6 dogs. Four dogs survived to hospital discharge. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that massive transfusion is possible and potentially successful in dogs. Predictable changes in electrolyte concentrations and platelet count develop.