ACVIM consensus statement on the treatment of immune thrombocytopenia in dogs and cats.

Management of immune thrombocytopenia (ITP) in dogs and cats is evolving, but there are no evidence-based guidelines to assist clinicians with treatment decisions. Likewise, the overall goals for treatment of ITP have not been established. Immunosuppressive doses of glucocorticoids are the first line treatment, but optimal treatment regimens beyond glucocorticoids remain uncertain. Additional options include secondary immunosuppressive drugs such as azathioprine, modified cyclosporine, and mycophenolate mofetil, usually selected based on clinician preference. Vincristine, human IV immunoglobulin (hIVIg), and transfusion of platelet or red blood cell-containing products are often used in more severe cases. Splenectomy and thrombopoietin receptor agonists are usually reserved for refractory cases, but when and in which patient these modalities should be employed is under debate. To develop evidence-based guidelines for individualized treatment of ITP patients, we asked 20 Population Intervention Comparison Outcome (PICO) format questions. These were addressed by 17 evidence evaluators using a literature pool of 288 articles identified by a structured search strategy. Evidence evaluators, using panel-designed templates and data extraction tools, summarized evidence and created guideline recommendations. These were integrated by treatment domain chairs and then refined by iterative Delphi survey review to reach consensus on the final guidelines. In addition, 19 non-PICO questions covering scenarios in which evidence was lacking or of low quality were answered by expert opinion using iterative Delphi surveys with panelist integration and refinement. Commentary was solicited from multiple relevant professional organizations before finalizing the consensus. The rigorous consensus process identified few comparative treatment studies, highlighting many areas of ITP treatment requiring additional studies. This statement is a companion manuscript to the ACVIM Consensus Statement on the Diagnosis of Immune Thrombocytopenia in Dogs and Cats.

Multi-institutional retrospective study investigating blood culture protocols and test positivity in 701 dogs.

Objectives: (i) To determine the influence of specimen collection protocol (timing and specimen quantity), primary disease process, and pre-existing antimicrobial or immunosuppressive therapy on blood culture (BC) positivity and (ii) To determine agreement between urine culture and BC results. Animals: 701 client-owned dogs. Methods: Multi-institutional retrospective study (2019-2022). Mixed-effect logistic regression was used to determine whether primary disease process, the number of BCs, or the timing of specimen collection was associated with BC positivity. Prediction plots were generated. Associations between urine culture and BC results were performed using logistic regression. Results: Dogs with a positive urine culture were more likely to have a positive BC (OR: 4.36, 95% CI: 2.12-8.97, p = 0.003). Dogs that had three BC specimens had the greatest odds of obtaining a positive BC result (adjusted predictive value: 0.44, 95% CI: 0.21-0.70), although this was not significant. Isolates from 38.5% of dogs with a positive BC had resistance to ≥3 antimicrobial classes. The timing between specimen collection had no significant association with BC positivity. Pre-existing antibiotic or immunosuppressive therapy had no significant association with BC positivity. Clinical relevance: Dogs with a positive urine culture were more likely to have a positive BC result.

Adverse effects of trazodone in dogs on primary hemostasis and electrocardiogram: A single-blinded placebo-controlled crossover study.

BACKGROUND: Trazodone is a serotonin antagonist/reuptake inhibitor medication commonly used for anxiety in dogs. Therapy with selective serotonin reuptake inhibitors in humans is associated with bleeding disorders and increased arrhythmogenesis. HYPOTHESIS/OBJECTIVES: To evaluate markers of primary hemostasis and corrected QT (cQT) interval in dogs before and after oral administration of standard dosages of trazodone or placebo. ANIMALS: Fifteen apparently healthy, client-owned dogs. METHODS: A single-blinded, randomized placebo-controlled crossover study was performed. Dogs were administered trazodone (5 to 7.5 mg/kg PO Q12h) or placebo. [Correction added after first online publication on 14 October 2023. In the abstract (methods) section (57.5 mg/kg PO Q12h) changed as (5 to 7.5 mg/kg PO Q12h).] Buccal mucosal bleeding time (BMBT), platelet count, platelet aggregation via Plateletworks, PFA-100 closure time and cQT interval were measured. A Shapiro-Wilk test was performed followed by either a paired t test or a Wilcoxon signed-rank test. RESULTS: No significant difference was detected in the BMBT, PFA-100 closure times, platelet counts, and cQT interval between trazodone or placebo. However, using Plateletworks, there was a significant decrease in platelet aggregation after administration of trazodone (95%; 81-97 vs 62%; 39-89, P = .002) and not placebo (95%; 81-97 vs 91%; 81-96, P = .21). CONCLUSIONS: It is unknown if this represents a clinically relevant change or if dogs with preexisting impairment in primary hemostasis or receiving higher dosages or longer durations of trazodone could have a more substantial change in hemostatic variables.

Evaluation of platelet additive solution for prolonging storage of functional canine platelet concentrate.

OBJECTIVE: To assess storage lesion development, platelet function, and bacterial growth in canine platelet concentrates (PCs) stored in a platelet additive solution (PAS) or a plasma control at 4°C for 21 days. DESIGN: Prospective, ex vivo, experimental controlled study. SETTING: University veterinary teaching hospital. ANIMALS: Ten units of canine PCs collected from blood bank donations. INTERVENTIONS: The PCs were separated into 2 bags, 1 containing 100% plasma and the other containing 35% plasma and 65% of a PAS (Plasma-Lyte A), and stored at 4°C for 21 days. At days 0, 7, 14, and 21, PCs were analyzed for the presence of swirling, aggregate formation, platelet counts, platelet indices, glucose, lactate, lactate dehydrogenase, Pvco2 , Pvo2 , aggregation via light aggregometry, activation percentages using flow cytometry, and bacterial growth. MEASUREMENTS AND MAIN RESULTS: Cold-stored PCs in both PAS and plasma control maintained mean pH >6.8 and mean lactate <9.0 mmol/L over 21 days, with no difference in glucose utilization. Swirl was maintained in both solutions for most days (76/80 combined total samples), with no difference in aggregate formation between solutions. The Pvco2 was higher in plasma on all days (P < 0.001), with no difference in Pvo2 . Platelet indices did not reflect significant storage lesion development in either solution. Lactate dehydrogenase did not differ between solutions but did increase from day 7 to day 21. Mean maximal aggregation percentage was reduced overall but with no significant difference between solutions. The only observed difference in mean activation percentage between solutions was in PAS on day 7, which was significantly higher than plasma (P < 0.05). No bacterial growth occurred during storage. CONCLUSIONS: Cold storage in PAS and plasma allowed PCs to be stored for up to 21 days with minimal storage lesion development, maintenance of platelet function, limited platelet activation, and no bacterial growth within stored bags.

Ionized calcium-to-phosphorus ratio predicts neoplasia in azotemic dogs: a retrospective study of 105 cases.

OBJECTIVE: To evaluate dogs with total hypercalcemia, azotemia, and normal serum phosphorus concentrations to determine whether a calcium-to-phosphorus ratio (Ca:P) or ionized Ca:P (iCa:P) could be utilized to predict underlying neoplasia. ANIMALS: 105 dogs were included in the study. Thirty-seven percent (n = 39) had known neoplasia, and 63% (66) had no evidence of neoplasia. PROCEDURES: A retrospective medical records search was performed. An observational cutoff of 2.5 for Ca:P and 0.33 for iCa:P was used for determining sensitivity and specificity between the neoplasia and nonneoplasia groups. RESULTS: Total hypercalcemia was higher in dogs with neoplasia compared to nonneoplastic cases of hypercalcemia. Ca:P of 2.5 had an 80% sensitivity and 46% specificity for predicting neoplasia. iCa:P of 0.33 had a 92% sensitivity and 77% specificity for predicting neoplasia in azotemic dogs. CLINICAL RELEVANCE: The sensitivity and specificity of Ca:P was low, making it an unreliable tool to predict neoplasia in this specific study population. However, iCa:P may have some usefulness in determining presence of neoplasia in patients with high calcium, azotemia, and normal phosphorus.

The effects of additive solutions on the development of storage lesions in canine platelet concentrates stored at 4°C.

OBJECTIVE: To assess platelet storage lesion development as evaluated by measurement of metabolic markers, platelet activation markers, and aggregometry, and determine the occurrence of bacterial growth in platelets stored in platelet additive solution (PAS) at 4°C for 7 days. DESIGN: Prospective, ex vivo experimental controlled study. SETTING: Research laboratory of a university veterinary teaching hospital. ANIMALS: Ten units of canine platelet concentrate collected from blood bank donations. INTERVENTIONS: Concentrates were aliquoted into 4 separate bags containing 100% plasma (control) or 30% plasma and 70% of a PAS (Plasma-Lyte A, Isoplate, or InterSol). Samples were stored at 4°C without agitation. At days 0, 3, 5, and 7, samples were analyzed for platelet count, mean platelet volume, glucose, lactate, lactate dehydrogenase, Po2 , Pco2 , degree of swirling, aggregate formation, aggregation via light aggregometry, surface P-selectin via flow cytometry, and bacterial contamination via culture. MEASUREMENTS AND MAIN RESULTS: Development of storage lesions was minimal, demonstrated by maintenance of a mean pH > 7.2 and mean lactate values <6 mmol/L at day 7 in all solutions. Glucose utilization did not vary significantly between any of the solutions. No significant difference was found between plasma and PAS for Po2 and Pco2 . P-selectin expression measured via flow cytometry showed a low platelet activation percent in all the solutions. InterSol had the lowest mean maximum percent aggregation (P < 0.001) and Isoplate the highest (P < 0.05). The mean maximum percent aggregation increased between day 0 and day 7 in all solutions. No bacterial growth was found in any of the solutions. CONCLUSIONS: Overall, PASs were comparable to plasma for the cold storage of platelets. Cold-stored platelets showed minimal storage lesion development with no bacterial growth. Plasma-, Plasma-Lyte A-, and Isoplate-stored platelets maintained function for up to 7 days at 4°C.

Use of a videofluoroscopic feeding evaluation to guide management of dogs with congenital idiopathic megaoesophagus.

BACKGROUND: Evidence-based guidelines for determining dietary management in dogs with megaoesophagus are lacking. OBJECTIVES: This study looked to compare oesophageal clearance times (ECT) of liquid and two food consistencies using a contrast videofluoroscopy feeding evaluation, and to assess if recommendations made based on findings could improve regurgitation and quality of life in dogs with congenital megaoesophagus. METHODS: Twenty-one dogs with congenital megaoesophagus and nine healthy dogs received liquid, slurry, and meatball diets containing barium while in an upright position. Follow-up was performed to determine response to recommendations. RESULTS: Healthy dogs had significantly shorter median ECT for all consistencies (p < 0.001). In the megaoesophagus group, ECT varied by consistency and individual. The number of dogs in the megaoesophagus group with complete clearance was four (median ECT 10 min) for liquid, five (median ECT 5 min) for slurry, and two (median ECT 5 and 30 min, respectively) for meatballs. Partial clearance was seen in 11 dogs (median clearance 25%) with liquid, seven with slurry (median clearance 50%), and five with meatballs (median clearance 60%). Recommendations included altering current medications (13/21 dogs), diet consistency (6/21), time upright (12/21), water delivery (21/21), and adding activity (7/21). Regurgitation episodes/week decreased significantly from 5.5 to 2.5 (p < 0.001) at follow-up 3-5 weeks post-evaluation, with 95% of owners reporting improvement in quality of life. Seventy percent were alive 46-777 days after last recheck. Three dogs died from megaoesophagus associated complications (median survival 461 days after diagnosis). CONCLUSIONS: The findings of this study suggest that a videofluoroscopic feeding evaluation may help guide management of dogs with congenital megaoesophagus.

A randomized crossover study of compounded liquid sildenafil for treatment of generalized megaesophagus in dogs.

OBJECTIVE: To determine whether delivery of compounded liquid sildenafil directly to the stomach of dogs with megaesophagus (ME) would affect esophageal clearance, regurgitation frequency, body weight, or quality of life. ANIMALS: 10 client-owned otherwise healthy dogs with stable ME. PROCEDURES: A randomized crossover study was performed. Dogs received either sildenafil (1 mg/kg, PO, q 12 h) or a placebo for 14 days, followed by a 7-day washout period, then the opposite treatment for 14 days. Esophageal clearance time was assessed by means of videofluoroscopy prior to treatment and on day 1 of each treatment period. Owners maintained logs of regurgitation episodes and quality of life. RESULTS: Compounded liquid sildenafil moved into the stomach during 21 of 30 (70%) videofluoroscopy sessions. Sildenafil resulted in a significant reduction in the number of regurgitation episodes (median, 3.5 episodes/wk; range, 0 to 14.5 episodes/wk), compared with baseline (median, 6.5 episodes/wk; range, 1.5 to 19.5 episodes/wk) and the placebo (median, 4 episodes/wk; range, 0 to 28 episodes/wk), and a significant increase in body weight (median, 22.05 kg; range, 6 to 26.3 kg), compared with baseline (median, 21.55 kg; range, 5.1 to 26.2 kg) and the placebo (median, 22.9 kg; range, 5.8 to 25.9 kg). There were no differences in esophageal clearance times or quality-of life-scores between sildenafil and placebo. CLINICAL RELEVANCE: Although significant differences with placebo administration were identified, clinically relevant improvements were not seen with the use of compounded liquid sildenafil in dogs with ME.

Development and implementation of a hemovigilance program at a university veterinary teaching hospital.

OBJECTIVE: To describe the development and implementation of a small animal hemovigilance program at a university veterinary teaching hospital. DESIGN: Retrospective observational descriptive study performed between October 2014 and March 2019. SETTING: University teaching hospital. ANIMALS: Dogs and cats receiving blood product transfusions . INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS:  A hemovigilance working group composed of veterinary specialists in clinical pathology, internal medicine, and emergency and critical care was established. This group developed evidence-based definitions of transfusion reactions, reaction classification systems, and a transfusion reaction reporting form. The reporting form contained sections for patient information, transfusion information, administration details, and reaction details. Reaction events were classified by reaction type, severity grade, and imputability to the transfusion. Following implementation of the hemovigilance program, transfusion reaction data were collected and examined for the period spanning October 2014 and March 2019. During the study period, 718 canine transfusions (4 whole blood, 400 packed RBC [pRBC], 300 fresh frozen plasma [FFP], 7 platelet rich plasma, and 7 cryoprecipitate) and 124 feline transfusions (5 whole blood, 95 pRBC, and 24 FFP) were administered. There were 32 total reactions (27 canine and 5 feline), with the most common reaction being febrile nonhemolytic transfusion reactions (19/32; 59%). The incidence rate of transfusion reactions was found to be 3.8% in dogs and 4.0% in cats. For the confirmed reactions, classification criteria for case definition, reaction severity grade, and imputability were able to be determined and recorded. This allowed targeted interventions to be implemented in order to potentially reduce future reactions. CONCLUSIONS: A hemovigilance program can be instituted successfully in a veterinary hospital setting and once developed, standardized reporting tools could be utilized by multiple hospitals and provide the basis for more widespread reaction reporting in veterinary medicine.

The effects of additive solutions on the development of storage lesions in stored canine platelet concentrates.

OBJECTIVE: To determine if platelet additive solutions (PAS) decrease the occurrence and degree of platelet storage lesions, maintain platelet function, and extend storage time in vitro beyond 5 days at 22°C when compared to platelets stored in plasma only. DESIGN: Prospective, ex vivo experimental controlled study. SETTING: Research laboratory in a school of veterinary medicine. ANIMALS: Twelve units of canine platelet concentrate prepared from fresh whole blood donations. INTERVENTIONS: Platelet concentrates were aliquoted into 4 units and stored at room temperature (22°C) under constant agitation in either 100% plasma (control) or 35% plasma and 65% of 1 of 3 different PAS (Plasma-Lyte A, Isoplate, and InterSol) for 7 days. At days 0, 3, 5, and 7, samples were analyzed for presence of swirling, degree of aggregate formation, platelet count, platelet indices, glucose, lactate, lactate dehydrogenase, Pvo2 , and Pvco2 concentrations, aggregation via light aggregometry, and activation percentage based on flow cytometric measurement of surface P-selectin. Bacterial cultures were performed on days 0, 5, and 7. MEASUREMENTS AND MAIN RESULTS: Isoplate had a higher incidence of aggregate formation on day 0 (n = 2), and Plasma-Lyte A had a higher incidence of loss of swirl on day 7 (n = 5). Plasma-stored samples had significantly higher platelet counts (P < 0.001), pH (P < 0.05), Pvco2 (P < 0.001), and lactate (P < 0.001), and significantly lower lactate dehydrogenase (P < 0.05) as compared to all PAS. The mean pH remained above 7.2 in PAS and plasma. There was no difference in platelet activation between plasma and PAS. Changes in platelet indices, glucose consumption, and maximum aggregation varied by storage solution. There was no bacterial growth seen in any samples. CONCLUSIONS: The 3 PAS performed similarly and could all be considered as potential replacements for plasma during the room temperature storage of canine platelet concentrate for up to 7 days.

Development and assessment of a formal learning module to educate veterinary students in an intensive care unit about transfusion reactions.

OBJECTIVE: To develop and assess the instructional efficacy of an online learning module on transfusion reactions in small animals and to evaluate participants' satisfaction of the module. DESIGN: Randomized controlled trial. SETTING: University teaching hospital. SUBJECTS: A total of 55, fourth-year veterinary students, 27 in a treatment group that received the learning module plus standard rotation training and 28 in a control group (no module) who received only standard training INTERVENTIONS: Students received a pretest on transfusion reactions followed by administration of a transfusion reaction learning module covering recognition, treatment, prevention, case examples, and self-assessment questions for 6 common transfusion reactions. Students also received a module satisfaction survey, a post-test at 2 weeks post-module, and a retention test at 6 weeks post-module. MEASUREMENTS AND MAIN RESULTS: Previous transfusion medicine exposure did not affect pretest scores and there was no difference in pretest scores between groups. The module group scored higher on the post-test (P < 0.001) and retention test (P = 0.002) than the control group. Mean post-test scores were 74.4% and 57.7% and mean retention test scores were 80.6% and 56.5% for the module and control groups, respectively. The module group scored higher on posttest and retention questions involving reaction recognition (P < 0.001). Students were overall very satisfied with the module with an average score of 4.8 (1-5). CONCLUSIONS: A transfusion reaction instructional module can be delivered successfully to veterinary students on an ICU-based clinical rotation. Students taking the module scored significantly better on post-assessments up to 6 weeks after module administration as compared to students receiving only conventional clinical rotation training.

Technique for Evaluation of Gravity-Assisted Esophageal Transit Characteristics in Dogs with Megaesophagus.

Movement of food material in the esophagus during upright feeding in dogs with megaesophagus (ME) is poorly characterized. A standardized contrast videofluoroscopy technique was used to evaluate esophageal transit characteristics in dogs with ME while in an upright position. Twelve dogs with ME (congenital, acquired idiopathic, or secondary to myasthenia gravis) were placed in an upright position using Bailey chairs and given liquid barium, canned food meatballs, and their normal diet consistency if different than meatballs. Passage of ingesta was videofluoroscopically evaluated by direct observation and change in ingesta area as determined by manual tracing or barium column product calculations. Significant individual variation was seen. Complete esophageal clearance of liquid was seen in four dogs, and complete clearance of meatballs in three dogs, with a median time of 5 min for both. Two of seven dogs fed a slurry diet had complete clearance by 10 min. No significant difference was found between area calculated via tracing or barium column product. Based on imaging results, alterations in food consistency, duration upright, or medication were recommended for nine dogs. In dogs with ME accustomed to a Bailey chair, contrast videofluoroscopy was technically straightforward and allowed for more specific physician-guided management recommendations.

Survey of owners on population characteristics, diagnosis, and environmental, health, and disease associations in dogs with megaesophagus.

Megaesophagus affects dogs worldwide but limited information is available regarding its characteristics in the general population of dogs. The objectives of this study were to provide information on a large population of dogs diagnosed with megaesophagus in regards to population characteristics, medical and family history, diagnosis, concurrent disease, and predisposing factors. A link to a web-based survey was provided on megaesophagus support websites and 838 eligible surveys were evaluated. Breeds most frequently associated with congenital megaesophagus were German shepherds, mixed breed "goldendoodles", Labrador retrievers, great Danes, and dachshunds. Breeds most often associated with acquired megaesophagus were Labrador and golden retrievers, Chihuahuas, boxers, German shepherds, dachshunds, and Rottweilers. Diagnosis was most often by a general practitioner (63.6%) via plain radiographs (63.3%) and/or barium study (45%). Congenital megaesophagus was diagnosed in 41.3% of dogs and persistent right aortic arch in 4.3%. Diseases most commonly associated with acquired megaesophagus were myasthenia gravis (19.3%), esophagitis (10.8%), hypothyroidism (8.8%). Survey results support previous breed predilections and identified dachshunds, boxers, Chihuahuas, Rottweilers, and "goldendoodles" as additional at risk breeds. Myasthenia gravis was found at lower rates than previous described and contrary to recent studies, hypothyroidism was found in relatively high prevalence. Most dogs were diagnosed by a general practitioner suggesting previous studies at referral facilities may be biased towards dogs with more severe disease and worse outcomes.

Investigation into the causes of aspirin resistance in healthy dogs.

Antiplatelet effects of acetylsalicylic acid (ASA, aspirin) may be poor in some individuals. Additionally, no method exists for predicting poor ASA response (resistance) in individual dogs. This study's main objective was to determine whether poor ASA response results from pharmacodynamic or pharmacokinetic causes. ASA concentrations causing 50% inhibition of platelet aggregation (in vitro IC50) were determined using whole blood collected from 21 drug-free healthy dogs to evaluate intrinsic sensitivity of platelets to ASA. Dogs were then administered ASA at 4 mg/kg once orally. Percent decrease in platelet aggregation from baseline, and plasma ASA and salicylic acid (SA) concentrations (expressed as AUC values) were measured for up to 3 hr. By 3 hr, 13/21 (62%) dogs showed >50% aggregation inhibition, while 8/21 (38%) dogs showed <50% inhibition. Aggregation inhibition values were negatively correlated with in vitro IC50 values (Rs = -0.49; p = 0.028) and positively correlated with ASA concentrations (Rs = 0.48; p = 0.03). Furthermore, ASA concentrations were strongly negatively correlated (Rs = -0.88; p < 0.001) with SA/ASA concentration ratios, an index of ASA metabolism to SA by esterase enzymes. Multiple linear regression analysis indicated that 59% (p < 0.001) of interindividual variability in aggregation inhibition was explained by in vitro IC50 values (29% of variability) and ASA concentrations (29% of variability). Consequently, poor in vivo ASA response in these dogs resulted from both pharmacodynamic (decreased platelet sensitivity) and pharmacokinetic (lower ASA concentrations) causes. Lower ASA concentrations may be explained by reduced bioavailability associated with higher esterase activities.

In vitro and in vivo assessment of platelet function in healthy dogs during administration of a low-dose aspirin regimen.

OBJECTIVE: To assess the in vitro and in vivo platelet function of healthy dogs during administration of a low-dose aspirin regimen. ANIMALS: 16 dogs. PROCEDURES: Dogs received aspirin (1 mg/kg, PO, q 24 h) for 7 days. Blood and urine samples were collected before (day 1; baseline) and on days 3 and 7 of the low-dose aspirin regimen. Platelet function was evaluated by use of turbidimetric and conventional impedance aggregometry, multiple-electrode impedance aggregometry, a platelet function analyzer (PFA), and determination of urine 11-dehydro-thromboxane B2 concentration. Turbidimetric aggregometry results were compared with the results obtained by the other 4 methods. Fourteen days after cessation of aspirin, platelet-rich plasma was incubated with acetylsalicylic acid and platelet function was assessed by turbidimetric aggregometry to determine whether this technique could accurately identify dogs that responded to the low-dose aspirin regimen. RESULTS: Of the 16 dogs, 13 had turbidimetric and conventional impedance aggregometry results that were decreased by > 25% from baseline on days 3 and 7, and 4 and 7 dogs had PFA closure times > 300 seconds on days 3 and 7, respectively. The median urine 11-dehydro-thromboxane B2 concentration-to-creatinine concentration ratio decreased by 49% between days 1 and 7. Turbidimetric aggregometry results were correlated with conventional impedance aggregometry results. There was poor agreement between the turbidimetric aggregometry and PFA results. The multiple-electrode impedance aggregometry protocol failed to reliably detect aspirin-induced platelet dysfunction. In vitro incubation of platelet-rich plasma with acetylsalicylic acid followed by turbidimetric aggregometry did not predict whether dogs responded to the low-dose aspirin regimen. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that the response to a low-dose aspirin regimen varied among healthy dogs.