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Objectives: To evaluate the safety and efficacy of human intravenous immunoglobulin in dogs with newly diagnosed malignancy and presumed secondary immune-mediated thrombocytopenia., Materials and Methods: Twelve client-owned dogs with newly diagnosed malignant disease and presumed secondary immune-mediated thrombocytopenia were prospectively enrolled to receive a single infusion of human intravenous immunoglobulin at a dose of 0.5 to 1 mg/kg intravenous over 8 hours. A complete treatment response was defined as a platelet estimation of ≥40,000 platelets/μL within 24 hours and a partial response within 48 hours from the completion of human intravenous immunoglobulin infusion. No treatment response was defined as a platelet estimation remaining <40,000 platelets/μL over 48 hours from the completion of the human intravenous immunoglobulin infusion. This pilot study had a prospective, open-label, uncontrolled design., Results: Out of the 12 enrolled dogs, seven completed the study. A complete treatment response to human intravenous immunoglobulin was identified in one lymphoma dog and a partial response was noted in another lymphoma dog. The remaining 10 dogs had no response to human intravenous immunoglobulin. No clinically relevant adverse reactions to human intravenous immunoglobulin occurred in any of the 12 initially enrolled dogs during the infusion and over a 3-month follow-up period for the seven surviving dogs., Clinical Significance: The results of this study suggest that the use of human intravenous immunoglobulin in dogs with newly diagnosed malignant disease and presumed secondary immune-mediated thrombocytopenia appears safe, but not effective for the treatment of thrombocytopenia. Larger multi-centre, prospective, double-blinded, placebo-controlled, outcome-based, malignancy-specific studies are needed to further evaluate these preliminary findings., (© 2024 British Small Animal Veterinary Association.)

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., (© 2024 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Objective: To describe the short-term response, early prognostic markers, and survival after treatment of canine immune-mediated thrombocytopenia (ITP) with human intravenous immunoglobulin (hIVIG) and methylprednisolone., Design: Retrospective cohort study., Settings: Private referral veterinary medical center., Animals: Twenty-seven client-owned dogs with primary or secondary ITP., Interventions: All dogs received 2 mg/kg IV methylprednisolone once daily and a single infusion of 5% hIVIG administered over 6-12 hours., Measurements and Main Results: A substantial increase in platelet count within 60 ± 12 hours post-hIVIG infusion (T 60 ) was observed in 19 of the 27 (70%) dogs with ITP (responders). Thirty-four variables, including serum immunoglobulin (Ig) G concentration 24 ± 12 hours post-hIVIG infusion (T 24 IgG) and increase in serum IgG concentration 24 ± 12 hours post-hIVIG infusion (T 24 Δ IgG ), were compared between responders and nonresponders at 5 different time points. Mortality rates of responders and nonresponders were evaluated 14 days post-hIVIG infusion. Serum T 24 IgG and serum T 24 Δ IgG were both significantly higher at T 60 in responders. All responders were alive 14 days post-hIVIG infusion, and their mortality rate was significantly lower compared with nonresponders., Conclusions: Responder dogs had an excellent 14-day survival rate. Serum T 24 IgG and serum T 24 Δ IgG concentrations accurately predicted response status at 60 hours post-hIVIG infusion., (© Veterinary Emergency and Critical Care Society 2024.)

Objective: To describe leflunomide as an adjunctive therapy in the treatment of non-associative immune-mediated thrombocytopenia., Materials and Methods: A retrospective study of dogs with a diagnosis of non-associative immune-mediated thrombocytopenia treated with leflunomide March 2008 to September 2021 was conducted. Data collected included signalment, clinical signs, physical examination findings and diagnostic testing performed. Medications administered, duration of hospital stay, time to platelet concentration >150×10 9 /L and adverse events during leflunomide therapy were recorded. Relapses within a year of diagnosis were reported., Results: A total of 20 client-owned dogs met inclusion criteria. Nineteen of 20 dogs (95%) achieved a platelet concentration >150×10 9 /L with leflunomide and prednisone combination therapy and four dogs (21.1%) relapsed during treatment or shortly after treatment. Adverse effects included diarrhoea (n=5), mild lymphopenia (n=9) and mild intermittent anaemia (n=1). A single dog developed hepatotoxicity presumed to be secondary to leflunomide therapy that resolved after drug discontinuation. One dog was treated for aspiration pneumonia during treatment. Two dogs were euthanased while receiving leflunomide., Clinical Significance: Length of hospitalisation, time to platelet recovery, treatment response and relapse rate were comparable with alternative treatment protocols. Most adverse effects did not require leflunomide dose adjustment; however, two dogs died while undergoing leflunomide treatment and there is compelling evidence that one of these dogs experienced fatal infection secondary to immune-suppression. Hepatotoxicity remains a known complication of leflunomide treatment and serial biochemistry testing is recommended., (© 2024 British Small Animal Veterinary Association.)

Objectives: To systematically review available evidence to determine when small animals at risk of thrombosis should be treated with antiplatelet agents and anticoagulants, which antiplatelet and anticoagulant agents are most effective, and when multimodal therapy is indicated., Design: Standardized, systematic evaluation of the literature, categorization of relevant articles according to level of evidence (LOE) and quality (Good, Fair, or Poor), and development of consensus on conclusions via a Delphi-style survey for application of the concepts to clinical practice. Draft recommendations were presented at 2 international veterinary conferences and made available for community assessment, review, and comment prior to final revisions and publication., Settings: Academic and referral veterinary medical centers., Results: Databases searched included Medline via PubMed and CAB abstracts. Twelve Population Intervention Comparison Outcome questions were devised and generated corresponding worksheets investigating indications for use of antithrombotic drugs in small animals. Seventy-eight studies were reviewed in detail. Most studies assessed were experimentally controlled laboratory studies in companion animals (56 LOE 3) with smaller numbers of LOE 2 (1), LOE 4 (5), LOE 5 (6), and LOE 6 (4) studies assessed. Only 5 randomized controlled clinical trials were identified (LOE 1, Good-Fair). The 12 worksheets generated 21 guidelines with 17 guideline statements that were refined during 3 rounds of Delphi surveys. A high degree of consensus was reached across all guideline recommendations during the Delphi process., Conclusions: Overall, systematic evidence evaluations generated 2 strong recommendations, 19 weak recommendations (formulated as suggestions), 9 situations where the evidence was insufficient to make strong recommendations, and 8 situations where no relevant evidence was retrieved to aid guideline generation. Numerous significant knowledge gaps were highlighted by the evidence reviews undertaken, indicating the need for substantial additional research in this field., (© Veterinary Emergency and Critical Care Society 2019.)

Objectives: To systematically examine the evidence for use of a specific protocol (dose, frequency, route) of selected antithrombotic drugs, in comparisons to no therapy or to other antithrombotic therapies, to reduce the risk of complications or improve outcomes in dogs and cats at risk for thrombosis., Design: Standardized, systematic evaluation of the literature, categorization of relevant articles according to level of evidence (LOE) and quality (Good, Fair, or Poor), and development of consensus on conclusions via a Delphi-style survey for application of the concepts to clinical practice., Settings: Academic and referral veterinary medical centers., Results: Databases searched included Medline via PubMed and CAB abstracts. Eight different antithrombotic drugs were investigated using a standardized Patient, Intervention, Comparison, Outcome (PICO) question format both for dogs and cats, including aspirin, clopidogrel, warfarin, unfractionated heparin (UFH), dalteparin, enoxaparin, fondaparinux, and rivaroxaban, generating a total of 16 worksheets. Most studies identified were experimental controlled laboratory studies in companion animals (LOE 3) with only four randomized controlled clinical trials in companion animals (LOE 1)., Conclusions: Overall, evidence-based recommendations concerning specific protocols could not be formulated for most antithrombotic drugs evaluated, either because of the wide range of dosage reported (eg, aspirin in dogs) or the lack of evidence in the current literature. However, clopidogrel administration in dogs and cats at risk of arterial thrombosis, notably in cats at risk of cardiogenic thromboembolism, is supported by the literature, and specific protocols were recommended. Comparably, aspirin should not be used as a sole antithrombotic in cats with cardiomyopathy. Using the available safety profile information contained in the literature, the panel reached consensus on suggested dosage schemes for most antithrombotics. Significant knowledge gaps were highlighted, which will hopefully drive novel research., (© Veterinary Emergency and Critical Care Society 2019.)

Objective: To describe a population of sick dogs administered rivaroxaban monitored with a rivaroxaban-calibrated anti-Xa activity assay (aXa)., Design: Descriptive retrospective study., Setting: Two veterinary teaching hospitals., Animals: Client-owned dogs administered rivaroxaban and monitored with aXa from January 2018 to January 2020 were eligible for study., Interventions: None., Measurements and Main Results: Medical records were reviewed and 19 dogs with a variety of underlying disease processes were identified. Rivaroxaban was administered to 12 of 19 dogs (63%) with confirmed thrombosis, 4 of 19 dogs (21%) with a strong clinical suspicion of thrombosis, and in 3 of 19 dogs (16%) with no current evidence of thrombosis. The median rivaroxaban dose administered was 0.96 mg/kg/day (0.62-1.58 mg/kg/day), with 15 of 19 dogs (79%) receiving rivaroxaban once daily. Clopidogrel was concurrently administered to 11 of 19 dogs (58%). Complete or partial thrombus resolution was identified in 5 of 12 (42%) and 3 of 12 (25%) dogs, respectively. Rivaroxaban appeared safe, with only 1 of 19 dogs (5%), concurrently administered clopidogrel, developing evidence of mild hematuria. Posttreatment monitoring revealed that 8 of 19 dogs (42%) had aXa below the target (aXa range of 150-250 ng/ml associated with effective treatment and prevention of venous thrombosis in people). The remaining 3 to 19 dogs (16%) achieved this range, and 8 of 19 dogs (42%) exceeded the range. No significant relationship between the initial rivaroxaban dose administered and the corresponding aXa result was identified. There were also no significant differences in baseline clinicopathological variables in dogs in which aXa fell within or outside this range., Conclusions: aXa was most commonly measured in dogs receiving rivaroxaban with confirmed or suspected thrombosis. Dogs in this study received a range of rivaroxaban dosages and attained variable aXa values that were not directly correlated with dosage., (© Veterinary Emergency and Critical Care Society 2022.)

Objectives: To determine the safety and efficacy of posaconazole and terbinafine for the treatment of naturally occurring sino-nasal aspergillosis in dogs refractory to conventional topical and systemic treatment., Materials and Methods: Ten client-owned dogs with sino-nasal aspergillosis and not responsive to conventional treatments were prospectively enrolled to receive a dose of 5 mg/kg posaconazole orally every 12 hours for six months. All dogs were concurrently treated with doses of 30 mg/kg terbinafine orally every 12 hours and 5 mg/kg doxycycline orally every 12 hours for 6 to 18 months., Results: All 10 enrolled dogs completed the study. The treatment response was defined as complete clinical remission (n=7) or partial clinical remission (n=3). Two dogs relapsed after cessation of combination therapy. All dogs lived more than one year after starting combination therapy and eight dogs are alive at the time of writing. No clinically relevant adverse reactions or increases in hepatic enzyme activity occurred during the combination therapy., Clinical Significance: The results of this study suggest that this combination therapy appears safe and well-tolerated for the treatment of refractory sino-nasal aspergillosis in dogs. Long-term survival is possible with prolonged treatment, but relapse is possible. Larger prospective studies are warranted to further evaluate these preliminary findings., (© 2017 British Small Animal Veterinary Association.)

A 2-year-old mixed breed dog presented with a 1-year history of crust and erosion on the nasal planum. Because histopathological examination revealed ruptured intraepidermal pustules and superficial dermal inflammation, the dog was diagnosed with pemphigus foliaceus. Human intravenous immunoglobulin was administered in two consecutive doses of 0.5 g/kg/day due to poor therapeutic response to previous immunosuppressive therapy. From Day 3 after the first dose of human intravenous immunoglobulin, tachypnoea, pale mucous membrane, haemoglobinuria and haemoglobinemia were observed, thus confirming haemolytic anaemia. Other drug-induced haemolytic anaemias were excluded because no additional drugs had been administered before the haemolysis occurred. Immune-mediated haemolytic anaemia was also excluded because the direct antiglobulin test was negative. Two transfusions were performed, and haemolysis was not observed from Day 4 of haemolytic anaemia onset. In conclusion, human intravenous immunoglobulin-induced haemolytic anaemia should be considered in dogs that develop haemolysis following the administration of human intravenous immunoglobulin., (© 2021 British Small Animal Veterinary Association.)

Objective: To describe the utility of Yunnan Baiyao (YB) alone or in combination with epsilon aminocaproic acid (EAC) for the treatment of dogs with echocardiographically identified right atrial (RA) masses and pericardial effusion (PE)., Design: Retrospective case-controlled study., Setting: Two private practice referral hospitals., Animals: Client-owned dogs with RA masses and PE identified echocardiographically over a 3-year period., Interventions: None., Measurements and Main Results: There were 67 dogs identified with RA masses and PE during the study period. Sixteen dogs were treated with YB alone while 8 dogs were treated with YB in combination with EAC in addition to pericardiocentesis. Forty-three dogs were treated with pericardiocentesis alone and were considered to be the control group. There was no difference between the groups in regards to signalment, physical examination abnormalities, and diagnostic test results on presentation. There was no significant difference between the 2 groups with respect to number of pericardiocenteses performed and there were no side effects attributed to the YB or EAC in any of the dogs. Median time to recurrence of clinical signs was not significantly different between the treatment (12 d, range 1-186 d) and control group (14.5 d, range 1-277 d). The median survival of dogs treated with YB alone or in combination with EAC (18 d, range 1-186 d) was also not significantly improved compared to dogs treated with pericardiocenteses alone (16 d, range 1-277 d)., Conclusions: This study suggests YB alone or in combination with EAC is relatively safe but does not significantly delay recurrence of clinical signs or improve survival in dogs with RA masses and PE. Due to the small cohort size, further prospective studies evaluating these drugs and their effects on hemostasis in dogs with RA masses and PE are warranted., (© Veterinary Emergency and Critical Care Society 2016.)

Objective: To evaluate the safety and tolerability of rivaroxaban (RIV), an oral direct factor Xa inhibitory drug, in dogs with presumed primary immune-mediated hemolytic anemia (pIMHA)., Design: Prospective, multicenter, positive-controlled, unblinded clinical trial. Client-owned dogs were enrolled between October 2012 and March 2014., Setting: Private referral centers., Animals: Twenty-four client-owned dogs with pIMHA. Enrolled dogs were randomized in 2 treatment groups to receive by mouth RIV or clopidogrel (CL) and low-dose aspirin (LDA). All dogs were monitored for 90 days from the enrollment in the study., Interventions: Enrolled dogs were given a standardized immunosuppressive protocol and RIV or CL and LDA., Measurements and Main Results: There was no identifiable adverse drug reaction, evidence of hemorrhage, significant prolongation of prothrombin time or activated partial thromboplastin time, or increase in transfusion requirements associated with RIV therapy compared to CL and LDA in dogs with pIMHA. There was no significant difference between treatment groups with respect to thrombotic events, survival rates to discharge, at 1 month and 3 months from diagnosis., Conclusions: This study suggests that RIV at a median dose of 0.89 mg/kg by mouth once daily was safe and well tolerated in a small group of dogs with presumed pIMHA able to tolerate oral medications and treated with a standardized immunosuppressive treatment protocol. Conclusions regarding the relative efficacy of RIV as compared to CL and LDA cannot be made due to the small size of the treatment groups and because pharmacodynamic effects were not assessed., (© Veterinary Emergency and Critical Care Society 2016.)

Objective: To describe the complications and frequency of thrombosis associated with the use of enoxaparin, a low molecular weight heparin, in dogs with primary immune-mediated hemolytic anemia (IMHA)., Design: Retrospective case series., Setting: Two privately owned veterinary referral hospitals., Animals: Twenty-one client-owned dogs with primary IMHA., Interventions: Dogs were treated with enoxaparin (0.8 mg/kg subcutaneously every 6 h) as the sole anticoagulation therapy starting at admission to the hospital., Measurements and Main Results: Only 2 dogs had minor hemorrhagic complications associated with enoxaparin therapy. Frequency of thrombosis was not assessed. Long-term survival was comparable to other anticoagulation protocols reported for dogs with primary IMHA., Conclusions: The use of enoxaparin was safe in a small group of dogs with primary IMHA. Whether enoxaparin therapy can reduce mortality and thrombotic complications in dogs with primary IMHA compared with other anticoagulation protocols remains unknown., (© Veterinary Emergency and Critical Care Society 2015.)

Objective: To describe the successful placement of an aortic stent graft in a dog suffering from aortic aneurysm and rupture., Case Summary: A 4-year-old neutered female mixed breed dog weighing 25 kg was presented with a chief complaint of acute onset of weakness and respiratory distress. On presentation, the dog was lateral and unresponsive, hypothermic, tachycardic, and tachypneic. Pleural effusion was identified in the right hemi-thorax on thoracic-focused sonographic scan for trauma. Thoracic radiographs showed a fluid/soft tissue opacity in the cranial mediastinum and pleural effusion on the right side. Thoracocentesis yielded noncoagulating blood. Hematology revealed normal PCV and total plasma protein that decreased within 24 hours to 20% and 50 g/L (20%/5.0 g/dL), respectively. The dog was treated with IV fluids, tranexamic acid, and fresh frozen plasma. An aortic aneurysm with irregular mineralization of the right ventrolateral aortic wall was identified on computed tomography examination, which also demonstrated a peri-aortic hematoma. A decision was made to attempt treatment with a stent graft. Under general anesthesia, a marker catheter was inserted into the esophagus. A 10-Fr sheath was inserted into the right femoral artery, and an angiography catheter was advanced over a wire. After angiography, a stent graft (12-mm × 50-mm) was placed over the guide wire and deployed under fluoroscopic guidance. The dog recovered uneventfully, with no evidence of recurrent bleeding, and was discharged 2 days after the procedure with antimicrobials, anthelmintic, and antithrombotic treatment. At 90-day follow-up, the dog was doing well, and stent position was radiographically confirmed., New or Unique Information Provided: This report describes successful management of aortic aneurysm and dissection, an uncommon and challenging pathology in the veterinary practice with few available treatment options. Stent graft placement is a minimally invasive procedure in which a covered stent is placed over the lesion to prevent rupture., (© Veterinary Emergency and Critical Care Society 2021.)

Human angiosarcoma and canine hemangiosarcoma reveal similarities not only in their aggressive clinical behaviour, but especially in molecular landscape and genetic alterations involved in tumorigenesis and metastasis formation. Currently, no satisfying treatment that allows for achieving long overall survival or even prolonged time to progression does not exist. Due to the progress that has been made in targeted therapies and precision medicine the basis for a new treatment design is to uncover mutations and their functions as possible targets to provide tailored drugs for individual cases. Whole exome or genome sequencing studies and immunohistochemistry brought in the last few years important discoveries and identified the most common mutations with probably crucial role in this tumour development. Also, despite a lack of mutation in some of the culprit genes, the cancerogenesis cause may be buried in main cellular pathways connected with proteins encoded by those genes and involving, for example, pathological angiogenesis. The aim of this review is to highlight the most promising molecular targets for precision oncology treatment from the veterinary perspective aided by the principles of comparative science. Some of the drugs are only undergoing laboratory in vitro studies and others entered the clinic in the management of other cancer types in humans, but those used in dogs with promising responses have been mentioned as priorities., (© 2023 John Wiley & Sons Ltd.)

Five dogs were presumptively diagnosed with immune-mediated thrombocytopenia. As they had all been chronically treated with non-steroidal anti-inflammatory drugs, administration of immunosuppressive doses of corticosteroids was considered contraindicated. Non-steroidal anti-inflammatory drugs were temporarily discontinued in all the dogs and mycophenolate mofetil was introduced as first-line single immunomodulatory therapy. This treatment protocol resulted in complete remission of immune-mediated thrombocytopenia in all the dogs, and mycophenolate mofetil was discontinued after several months of therapy in four of the five dogs with no relapses, even when non-steroidal anti-inflammatory drug administration was resumed. The remaining dog required continued mycophenolate mofetil therapy to avoid relapse. One dog experienced diarrhoea, and another dog had diarrhoea and decreased appetite., (© 2014 British Small Animal Veterinary Association.)

Objective: To report the outcome of doxorubicin-based chemotherapy as the sole treatment for dogs with echocardiographically identified right atrial masses and pericardial effusion., Methods: A retrospective study of case records of dogs with right atrial masses treated with doxorubicin. Dogs were excluded from the study if they had any type of surgery performed such as pericardiectomy or right atrial mass resection, or if their chemotherapy protocol did not include doxorubicin. The data collected included signalment, history, physical examination findings, diagnostic test results and long-term survival., Results: Dogs with right atrial masses and pericardial effusion that received doxorubicin-based chemotherapy alone had a median survival of 139 · 5 days (range 2 to 302 days). Chemotherapy side effects were frequent but mild., Clinical Significance: Doxorubicin-based chemotherapy alone appears to be a viable treatment option for dogs with echocardiographically identified right atrial masses and pericardial effusion., (© 2014 British Small Animal Veterinary Association.)

Objective: To describe a case of immune-mediated thrombocytopenia (IMT) after massive Africanized bee envenomation in a dog., Case Summary: While boarding at a kennel, a dog was stung by approximately 300 Africanized bees. During initial veterinary examination, the dog was deemed to be in shock, characterized by collapse, with hypotension, bradycardia, and hypoglycemia. In addition, severe diffuse erythema and edema were noted over the entire body. Supportive care, including IV crystalloid and colloid fluids, dextrose, fresh frozen plasma, oxygen therapy, broad spectrum antimicrobials, dexamethasone, and diphenhydramine was initiated. The dog's condition stabilized over the next 2 days. Forty-eight hours after admission the dog developed hematemesis and hematochezia, and severe thrombocytopenia was identified. Extensive diagnostic investigation revealed no likely trigger other than the Africianized bee exposure, and a diagnosis of IMT was made. Following a red blood cell transfusion and immunosuppressive doses of dexamethasone and gastroprotectant therapy, the dog's condition stabilized, and the platelet count returned to normal after 7 days from initiation of therapy., New or Unique Information Provided: IMT is a possible sequelae of massive Africanized bee envenomation in the dog., (© Veterinary Emergency and Critical Care Society 2013.)

Objective: To describe a clinical case of postresuscitation myocardial dysfunction in a dog., Case Summary: An 11-month-old, 2.37 kg female spayed Chihuahua was referred for management post CPR after suffering cardiopulmonary arrest. Postresuscitation a gallop rhythm was identified and an echocardiogram revealed severe left ventricular dilation and severely impaired myocardial contractility with a mild eccentric jet of mitral regurgitation on color Doppler interrogation. The primary differentials were idiopathic or nutritional dilated cardiomyopathy, end-stage myocarditis, or postresuscitation myocardial dysfunction. Echocardiogram was repeated 48 hours later and showed normal left ventricular dimensions and contractility assessed as consistent with postresuscitation myocardial dysfunction., New or Unique Information Provided: Postresuscitation myocardial dysfunction is a common complication of CPR in human medicine and is associated with a worse outcome. This is the first clinical report of postresuscitation myocardial dysfunction in a dog., (© Veterinary Emergency and Critical Care Society 2012.)

Background: A major cause of death in dogs with primary immune-mediated hemolytic anemia (pIMHA) is thrombotic disease. Ultralow-dose aspirin (ULDA) is commonly used to prevent thrombosis in dogs with pIMHA; however, the efficacy of antiplatelet agents in dogs with pIMHA is unknown., Hypothesis: The use of clopidogrel (CL), alone or in combination with ULDA, would improve survival to discharge and at 90 days without important adverse effects compared with ULDA alone in dogs with pIMHA treated with standard immunosuppressive therapy., Animals: Twenty-four client-owned dogs with pIMHA., Methods: Prospective, positive-controlled, unmasked clinical trial with dogs randomized in 3 treatment groups to receive PO ULDA or CL or both., Results: There was no identifiable adverse reaction, evidence of hemorrhage, or increase in transfusion requirements associated with CL therapy, either alone or combined with ULDA, compared with ULDA alone. There was no significant difference between treatment groups with respect to survival to discharge and at 90 days., Conclusions and Clinical Importance: This study suggests that CL therapy, alone or in combination with ULDA, was safe and had similar short-term survival compared with ULDA alone in a small group of dogs with pIMHA able to tolerate oral medications and treated with standard immunosuppressive treatment., (Copyright © 2010 by the American College of Veterinary Internal Medicine.)

Objective: To identify and characterize the syndrome of immune-mediated hemolytic anemia (IMHA) with concurrent severe thrombocytopenia (

Background: Immune-mediated thrombocytopenia (IMT) is a common hematologic disorder in dogs. Human intravenous immunoglobulin (hIVIG) may have a beneficial effect in canine IMT., Hypothesis: A single hIVIG infusion (0.5 g/kg) in dogs with presumed primary IMT (pIMT) is a safe adjunctive emergency treatment to accelerate platelet count recovery and shorten hospitalization time without increasing the cost of patient care., Animals: Eighteen client-owned dogs with a presumptive diagnosis of pIMT., Methods: Prospective, randomized, double-blinded, placebo-controlled clinical trial., Results: There were no identifiable immediate or delayed adverse reactions associated with hIVIG administration over a 6-month period. The median platelet count recovery time for the hIVIG group was 3.5 days (mean + or - SD: 3.7 + or - 1.3 days; range, 2-7 days) and 7.5 days (mean + or - SD: 7.8 + or - 3.9 days; range, 3-12 days) for the placebo group. The median duration of hospitalization for hIVIG group was 4 days (mean + or - SD: 4.2 + or - 0.4 days; range, 2-8 days) and 8 days (mean + or - SD: 8.3 + or - 0.6 days; range, 4-12 days) for the placebo group. There was no significant difference between groups with respect to expense of initial patient care, whereas significant reduction in platelet count recovery time (P= .018) and duration of hospitalization (P= .027) were detected in the hIVIG group., Conclusions and Clinical Importance: Compared with corticosteroids alone, adjunctive emergency therapy of a single hIVIG infusion was safe and associated with a significant reduction in platelet count recovery time and duration of hospitalization without increasing the expense of medical care in a small group of dogs with presumed pIMT.

An 11-year-old, spayed female miniature schnauzer with diabetes mellitus was presumptively diagnosed with Evans' syndrome (ES). Because of the potential adverse effects of immunosuppressive doses of glucocorticoids in a diabetic dog, a single infusion of human intravenous immunoglobulin and oral leflunomide were used as first-line immunomodulatory therapy, after informed owner consent was received. This treatment resulted in complete remission of the ES, and leflunomide was discontinued after 10 months of therapy. Over a 19-month follow-up, the dog did not relapse and has remained a well-regulated diabetic.

Background: Glucocorticoids with or without other immunotherapy are the initial treatment of choice for dogs with severe immune-mediated thrombocytopenia (IMT). The majority of treated dogs will have improvements in platelet counts within 5 to 7 days of starting therapy, but complications from hemorrhage often occur before a response is seen. Human IV immunoglobulin (hIVIG) blocks Fc receptors on mononuclear phagocytic cells in dogs; it is used in people with idiopathic thrombocytopenic purpura., Hypothesis: The purpose of this study was to describe adverse effects and benefit of hIVIG in addition to conventional immunosuppressive therapy in dogs with severe IMT., Animals: Five client-owned dogs with severe primary IMT., Methods: Case series. The hospital database was searched for dogs with primary IMT treated with hIVIG., Results: No adverse effects were noted during or after hIVIG infusion in any treated dog. Over a 6-month follow-up, all dogs were clinically normal when using conventional immunosuppressive therapy. Human IVIG was administered 3 days after initiation of immunosuppressive therapy in 4 dogs, and, after 2 days, in 1 dog. In all dogs, the mean platelet counts pre- and 24 hours post-hIVIG infusion (0.28-0.76 g/kg) were 2,500/pL and 50,600/microL (62,750/microL for the 4 responders), respectively. One dog failed to respond as promptly to hIVIG (0.34 g/kg), and the platelet count increased to 66,000/microL after 9 days of immunosuppressive therapy. The mean duration of hospitalization post-hIVIG in all 5 dogs was 1.8 days (12 hours for responders), and the mean total length of hospitalization was 4.6 days (3.5 days for responders). Active hemorrhage resolved and no packed red blood cell transfusions were required after hIVIG infusion for responders., Conclusions and Clinical Importance: Human IVIG was well tolerated and appeared to be associated with rapid platelet count recovery and amelioration of clinical signs in most dogs with IMT.

Objective: To compare viscoelastic parameters between healthy control dogs and dogs with primary immune-mediated hemolytic anemia (pIMHA) using a new, point-of-care viscoelastic coagulation monitor (VCM). a DESIGN: Retrospective study from 2017 to 2021., Setting: Three regional private referral centers., Animals: Eighteen client-owned dogs with pIMHA and 33 healthy control dogs. pIMHA dogs were defined based on established criteria., Interventions: None., Measurements and Main Results: Medical records of dogs with pIMHA and VCM performed at diagnosis from 2017 to 2021 and apparently healthy control dogs voluntarily enrolled in the blood donor program from 2017 to 2018 were reviewed. For the healthy control dogs, consent was obtained to perform VCM in addition to traditional screening. Compared to healthy control dogs, dogs with pIMHA had mean VCM parameters consistent with hypercoagulability, demonstrated by lower mean (SD) clot formation time (108 s [30] vs 233 s [55]; P < 0.0001), higher mean alpha angle (62 degrees [6] vs 52 degrees [6]; P < 0.0001), higher mean maximum clot formation (49 VCM units [11] vs 32 VCM units [5]; P < 0.0001), higher mean amplitude at 10 minutes (40 VCM units [11] vs 19 VCM units [3]; P < 0.0001), and higher mean amplitude at 20 minutes (47 VCM units [11] vs 25 VCM units [4]; P < 0.0001). pIMHA dogs also had significantly higher median (interquartile range) lysis index at 30 minutes (100% [100-100] vs 98% [90-100]; P < 0.0001). When compared to 3 established normal canine reference intervals, dogs with pIMHA had a significantly higher proportion of VCM variables (48%-57%) consistent with hypercoagulability, and a significant percentage of pIMHA dogs (78%-89%) had VCM tracings consistent with hypercoagulability overall, irrespective of the interval utilized for interpretation., Conclusions: This study demonstrates hypercoagulability in dogs with pIMHA when compared to healthy control dogs using VCM. Prospective evaluation is warranted to further characterize these findings as well as to evaluate their clinical impact., (© Veterinary Emergency and Critical Care Society 2022.)

Canine splenic hemangiosarcoma (HSA) is an aggressive tumour of vascular endothelium that carries a grave prognosis following standard of care treatment with surgery and doxorubicin. A previous pilot study revealed potential anti-tumour activity of I'm-Yunity polysaccharopeptide (PSP) for canine HSA. The aim of this prospective study was to assess patient outcome when treated with PSP alone or in combination with doxorubicin post-splenectomy compared to patients treated with surgery and doxorubicin that received a placebo in place of PSP. Dogs undergoing splenectomy for splenic HSA were eligible. Following splenectomy, owners were offered treatment with PSP alone or adjuvant doxorubicin chemotherapy (unblinded). Patients with owners that selected to proceed with doxorubicin chemotherapy were blindly randomized to receive placebo or PSP. Dogs were evaluated weekly for 15 weeks, then scheduled for monthly visits until death. One hundred and one dogs were included in the final analysis: 51 PSP alone, 25 doxorubicin/placebo, and 25 combination PSP/doxorubicin. On multivariate analysis, dogs treated with single agent PSP, female dogs, decreased haematocrit at diagnosis, and stage III disease were negatively significantly associated with outcome; however, an interaction between treatment group and sex was documented. Gender-specific outcomes revealed no significant difference in survival between treatment groups for male dogs, but female dogs treated with PSP alone had significantly reduced survival compared to females receiving doxorubicin/placebo (HR 0.21; p = .004). Anaemia (HR 5.28; p < .001) and stage III disease (HR 2.9; p = .014) remained negatively associated with survival when controlling for sex and treatment group. The addition of PSP to doxorubicin post-splenectomy did not improve survival in dogs with splenic HSA., (© 2022 John Wiley & Sons Ltd.)

Objective: To evaluate the evidence for the conservative and surgical management of pericardial effusions for neoplastic and idiopathic etiologies in dogs., Study Design: Systematic review., Sample Population: Peer-reviewed English-language articles describing the treatment and outcome of naturally occurring pericardial effusion in domestic dogs., Methods: A literature search was performed with PubMed, Cab Abstracts, Scopus, and Agricola in August 2019 for articles describing pericardial effusion treatment in dogs. Inclusion criteria were applied, and articles were evaluated for reported outcome and level of evidence by using The Oxford 2011 Levels of Evidence, a previously described hierarchical system, and GRADE (Grading of Recommendations, Assessment, Development and Evaluation)., Results: One hundred eight of the 641 unique articles that were identified and evaluated met inclusion criteria. Most articles included were case studies (68.2%) or retrospective case series (25.2%), with all articles providing a low level of evidence. The articles had inconsistent inclusion criteria, outcome measures, and follow-up, making comparison of outcomes difficult., Conclusion: Because of the low quality of evidence of the studies included in this systematic review and the variability of the outcomes, there is not sufficient evidence to recommend one treatment option rather than another., Clinical Significance: There is a requirement for higher quality evidence such as randomized controlled trials and prospective comparative cohort studies. Standardization of outcome measures reported for each treatment option and disease process studied will allow for better comparison of outcomes between studies., (© 2020 The American College of Veterinary Surgeons.)

Objective: To report on the spontaneous resolution of caval syndrome in 5 dogs selected for their response to medical stabilization prior to scheduled heartworm extraction., Series Summary: Five dogs with heartworm caval syndrome were treated with sildenafil, fluid, and supplemental oxygen therapy. Moreover, 4 of 5 dogs were also administered pimobendan to achieve hemodynamic stabilization in preparation for percutaneous heartworm extraction. Spontaneous heartworm migration back into the pulmonary arteries was detected from 2 h to 5 days after treatment initiation., Unique Information Provided: Unanticipated spontaneous resolution of caval syndrome was documented in a low number of dogs after initiation of a patient stabilization protocol aiming at improving right ventricular hemodynamics and reducing pulmonary artery pressure prior to scheduled heartworm extraction. At this time, it is unknown if intervention to improve the hemodynamic status of the animal prior to heartworm extraction improves procedure outcome, and which factors contributed to the migration of the heartworms back into the pulmonary arteries in these selected cases. Therefore, this approach cannot be recommended in place of current recommendations for treatment of caval syndrome., (© Veterinary Emergency and Critical Care Society 2020.)

Abnormal platelet activity can either lead to bleeding tendencies or inappropriate thrombus formation and can occur secondarily to a wide variety of disease processes, with a range of clinical consequences and severity. This article will discuss the pathophysiology of platelet function abnormalities and consider a logical diagnostic approach applicable to veterinary practice. Recent advances in platelet function testing will then be discussed, with regards to detection of platelet dysfunction and tailoring of pharmacological manipulation. Although many of these tests are still confined to research or academic institutions, techniques for indirectly assessing platelet function are starting to become more widely available. Although we still require further research to develop guidelines for the use of these tests in clinical decision-making, the recent advances in this field are an exciting step forward in being able to detect and manage platelet dysfunction in both primary care and referral practice., (© 2019 British Small Animal Veterinary Association.)

This case report describes a massive honey bee envenomation in a 14-month-old male Belgian Malinois dog from St. Kitts, West Indies. Acute and delayed onsets of hemolytic anemia, echinocytosis, spherocytosis, thrombocytopenia, hemoglobinemia, and hemoglobinuria developed following envenomation. The dog recovered after treatment with glucocorticoids and supportive therapy. Spherocytosis, hemolysis, and thrombocytopenia in patients with massive bee envenomation are likely due to the direct toxic effects of the primary components of bee venom, melittin and phospholipase A 2 (PLA 2 ). Mellitin causes hemolysis by forming large pores in erythrocytes resulting in leakage of hemoglobin and also causes spectrin stiffening and resultant echinocyte and spherocyte formation. Melittin also stimulates PLA 2 , a hydrolase that causes echinocytosis and spherocytosis, in vivo and in vitro, and mitochondrial breakdown in platelets. However, delayed manifestations could be attributed to immune-mediated mechanisms from the generation of antibodies against damaged erythrocytes and platelet membrane proteins., (© 2019 American Society for Veterinary Clinical Pathology.)

Background: Primary immune thrombocytopenia (pITP) in dogs presents a diagnostic challenge, and clinical markers of severity are lacking. Objectives: Identify clinicopathologic features that differentiate pITP from secondary ITP (sITP) and markers related to bleeding severity, transfusion, and survival of dogs with pITP. Animals: Ninety‐eight thrombocytopenic dogs (58 pITP and 40 sITP). Methods: Client‐owned dogs with platelet counts <50 000/μL were enrolled in a prospective, multi‐institution cohort study. History and treatment information, through a maximum of 7 days, was recorded on standard data forms. Bleeding severity was scored daily using a bleeding assessment tool (DOGiBAT). At‐admission blood samples were collected for CBC, biochemistry, C‐reactive protein concentration, and coagulation panels, and to measure platelet surface‐associated immunoglobulin G (PSAIg) and expression of platelet membrane proteins and phospholipids. Dogs with evidence of coincident disease were classified as sITP. Results: No definitive pITP diagnostic test was found. However, pITP cases were characterized by lower platelet counts, D dimer concentrations, and platelet membrane protein expression than sITP cases. Differentiation between pITP and sITP was further enhanced using logistic regression modeling combining patient sex, coagulation profile, platelet count, D dimer, and PSAIg. A second model of pITP severity indicated that low hematocrit and high BUN concentration were associated with non‐survival. Low hematocrit at admission, but not platelet count or DOGiBAT score, was associated with transfusion. Conclusions and Clinical Importance: Pending validation studies, models constructed from at‐admission clinicopathologic findings may improve differentiation of pITP from sITP and identify the most severe pITP cases at the time of presentation. [ABSTRACT FROM AUTHOR]

Background: Knowledge of additional risk factors for thrombotic disease (TD) among dogs with renal proteinuria is limited; these might differ for TD affecting the systemic arterial (AT), systemic venous (VT), and pulmonary circulation (PT). Hypothesis/Objectives: To compare signalment and clinicopathological data between dogs with renal proteinuria with or without TD, and between dogs with AT, VT, and PT. Animals: One hundred fifty client‐owned dogs with renal proteinuria, 50 of which had TD. Methods: Retrospective case‐controlled study. A database search (2004‐2021) identified proteinuric dogs (UPC > 2) with and without TD. Clinicopathological data were obtained from the records. TD and non‐TD (NTD) groups were compared by binary logistic regression, and AT, VT, and PT groups by multinomial regression. Normal data presented as mean ± SD, non‐normal data presented as median [25th, 75th percentiles]. Results: Cavalier King Charles Spaniels were overrepresented in the TD group (OR = 98.8, 95% CI 2.09‐4671, P =.02). Compared to NTD cases, TD cases had higher concentration of neutrophils (11.06 [8.92, 16.58] × 109/L vs 7.31 [5.63, 11.06] × 109/L, P =.02), and lower concentration of eosinophils (0 [0, 0.21] × 109/L vs 0.17 [0.04, 0.41] × 109/L, P =.002) in blood, and lower serum albumin (2.45 ± 0.73 g/dL vs 2.83 ± 0.73 g/dL, P =.04). AT cases had higher serum albumin concentrations than VT cases (2.73 ± 0.48 g/dL vs 2.17 ± 0.49 g/dL, P =.03) and were older than PT cases (10.6 ± 2.6 years vs 7.0 ± 4.3 years, P =.008). VT cases were older (9.1 ± 4.2 years vs 7.0 ± 4.3 years, P =.008) and had higher serum cholesterol concentration (398 [309‐692 mg/dL] vs 255 [155‐402 mg/dL], P =.03) than PT cases. Conclusions and Clinical Importance: Differences between thrombus locations could reflect differences in pathogenesis. [ABSTRACT FROM AUTHOR]

An 8‐year‐old, female, spayed Pembroke Welsh Corgi presented for a 3‐day history of worsening lethargy and pale pink mucous membranes. Hematological analysis revealed a normocytic, normochromic, regenerative anaemia, positive saline agglutination and marked thrombocytopenia, supportive of a diagnosis of immune‐mediated haemolytic anaemia and thrombocytopenia, either as a secondary result of immune‐mediated haemolytic anaemia or an additional immune‐mediated process. Due to continued decreases in packed cell volume despite immunosuppressive therapy and packed red blood cell transfusion, euthanasia was elected. Gross postmortem examination revealed cutaneous and visceral petechiae to ecchymoses, visceral icterus, and moderate splenomegaly. Microscopically, the bone marrow was hypercellular with moderate to marked increase in numbers of erythroid lineage cells relative to myeloid lineage cells. Few macrophages displayed erythrophagia. Given the drastically worsening thrombocytopenia, immune‐mediated thrombocytopenia was considered more likely, but this could not be entirely verified. This presentation of immune‐mediated haemolytic anaemia with thrombocytopenia illustrates the clinical diagnosis and management of immune‐mediated haematological diseases in dogs. [ABSTRACT FROM AUTHOR]

Background: Aortic and aortoiliac thrombosis in dogs causes disease and death. Objective: To describe the procedure and outcomes for stenting the caudal aorta and aortoiliac trifurcation. Animals: Seven client‐owned dogs that underwent aortic/aortoiliac stenting for treatment of thrombosis. Methods: Retrospective multi‐center investigation. Medical records were reviewed for dogs that underwent stenting of the aorta or aortoiliac trifurcation between 2008 and 2020. Information collected included history, signalment, clinicopathologic data, diagnostic imaging, procedure reports, and outcomes. Results: Seven dogs with an occlusive thrombus located at or near the aortic trifurcation were included. Four of 7 dogs were non‐ambulatory. Hind limbs were paretic in 5 dogs, paralyzed in 1 dog, and claudication alone was noted in 1 dog. Five of the 7 dogs had protein‐losing nephropathy (PLN). Of 5 dogs with PLN, 1 had protein‐losing enteropathy (PLE) and controlled hypothyroidism and 1 had caudal aortic chondrosarcoma. Two dogs had no identified underlying disease. Angiography was performed before catheter directed thrombolysis and stent placement. No deaths occurred during the procedure. Postoperative complications included pain (4/7), bruising and edema (3/7), bruising only (1/7), and edema only (1/7). Median survival time (MST) of the 7 dogs was 264 days (range, 1‐1053 days). Five of 7 dogs were ambulatory within 2 days of stenting and survived to discharge with a MST of 425 days (range, 208‐1053 days). Conclusions and Clinical Importance: Stenting of the aorta and aortoiliac trifurcation can provide an apparently safe and effective treatment with rapid return to ambulation for some dogs with aortic thrombosis. [ABSTRACT FROM AUTHOR]

Background: Information regarding adverse events (AEs) of mycophenolate mofetil (MMF) is limited. Objectives: To evaluate the types and frequency of potential AEs of MMF in dogs with immune‐mediated disease. Animals: One hundred thirty‐one dogs treated with MMF for management of suspected immune‐mediated disease. Methods: Retrospective study. Medical records were reviewed to find and group suspect AEs in gastrointestinal (GI), hematologic, and other categories. Age, dosage, body weight, and sex were analyzed between dogs with and without AEs by using the Mann‐Whitney U‐test and chi‐squared test. Results: The median starting dosage of MMF was 17.5 mg/kg/day (interquartile range [IQR] = 15.1‐20.6 mg/kg/day) and the median treatment duration was 56 days (IQR = 14‐236 days). Mycophenolate mofetil was prescribed for immune‐mediated hemolytic anemia (n = 31), immune‐mediated thrombocytopenia (n = 31), pemphigus foliaceus (n = 15), immune‐mediated polyarthritis (n = 12), and others (n = 42). Overall, potential AEs of MMF were observed in 34 of 131 dogs (GI 24.4% [31/127], neutropenia 4% [3/76], anemia 4% [1/25], thrombocytopenia 4.0% [1/25], and dermatologic 1.5% [2/131]). There were no significant differences among dogs with (n = 37) or without potential AEs (n = 94) in regards to sex, age, body weight, or dosage of MMF (P =.06,.13,.24, and.26, respectively). Conclusions and Clinical Importance: In the dogs administered MMF, GI AEs were most common. Since potential hematologic and dermatologic AEs developed in a few dogs, clinicians should be aware of these when prescribing MMF to dogs with immune‐mediated disease. [ABSTRACT FROM AUTHOR]

Therapeutic plasma exchange (TPE) is an emerging treatment for dogs with immune‐mediated diseases, but reports for treatment of immune‐mediated thrombocytopenia (IMT) are lacking. These case reports illustrate the application of centrifugal TPE in 4 dogs with IMT. All dogs presented with severe hemorrhage requiring ≥1 blood transfusions, were unresponsive to conventional treatment or both. Dogs were treated with 3 sequential centrifugal TPE sessions, totaling 4.0 to 4.9 total plasma volumes exchanged per dog. In 3 dogs, TPE was associated with improvement in clinical manifestations of bleeding and platelet count in combination with immunosuppressive drugs. One dog was euthanized after 3 treatments because of persistent severe thrombocytopenia and hemorrhage. Preliminary observations indicate that TPE is safe and may be a useful adjunct in the management of IMT that is severe or refractory to traditional treatment. [ABSTRACT FROM AUTHOR]

Background: Dogs with immune‐mediated disease often receive glucocorticoids with clopidogrel, but ulcerogenic effects of current protocols are unknown. Hypothesis/Objectives: To compare gastrointestinal endoscopic findings among dogs administered clopidogrel, prednisone, and combination treatment. Animals: Twenty‐four healthy research dogs. Methods: Double‐blinded, placebo‐controlled randomized trial. Dogs received placebo, clopidogrel (2–3 mg/kg q24h), prednisone (2 mg/kg q24h), or prednisone with clopidogrel PO for 28 days. Attitude, food intake, vomiting, and fecal score were determined daily. Clinicopathologic testing was performed at baseline and on day 28. Gastrointestinal hemorrhages, erosions, and ulcers were numerated by 2 blinded investigators for endoscopies performed on days 0, 14, and 28, and endoscopic mucosal lesion scores were calculated. Results were compared using mixed model, split‐plot repeated measures ANOVAs and generalized estimating equation proportional odds models as appropriate. P < .05 was considered significant. Results: Clinical signs of gastrointestinal bleeding were not noted. Endoscopic mucosal lesion scores differed significantly by group (F[3, 20] = 12.8, P < .001) and time (F[2, 40] = 8.3, P < .001). Posthoc analysis revealed higher lesion scores in the prednisone‐receiving groups (P ≤ .006 for each) and on day 14 (P ≤ .007 for each). Ulcers were identified in 4 dogs administered prednisone and 3 dogs administered prednisone/clopidogrel. Odds of having endoscopic mucosal lesion scores ≥4 were 7‐times higher for dogs in prednisone (95%CI 1.1, 43.0; P =.037) and prednisone‐clopidogrel (95%CI 1.1, 43.4; P =.037) groups than those in the placebo group. Conclusions and Clinical Importance: Gastrointestinal bleeding and ulceration occur commonly in healthy dogs administered prednisone or prednisone/clopidogrel treatment, but not clopidogrel monotherapy. Though lesions are severe in many cases, they are not accompanied by clinical signs. [ABSTRACT FROM AUTHOR]

Immune‐mediated hemolytic anemia (IMHA) causes severe anemia in dogs and is associated with considerable morbidity and mortality. Treatment with various immunosuppressive and antithrombotic drugs has been described anecdotally and in previous studies, but little consensus exists among veterinarians as to the optimal regimen to employ and maintain after diagnosis of the disease. To address this inconsistency and provide evidence‐based guidelines for treatment of IMHA in dogs, we identified and extracted data from studies published in the veterinary literature. We developed a novel tool for evaluation of evidence quality, using it to assess study design, diagnostic criteria, explanation of treatment regimens, and validity of statistical methods. In combination with our clinical experience and comparable guidelines for humans afflicted with autoimmune hemolytic anemia, we used the conclusions of this process to make a set of clinical recommendations regarding treatment of IMHA in dogs, which we refined subsequently by conducting several iterations of Delphi review. Additionally, we considered emerging treatments for IMHA in dogs and highlighted areas deserving of future research. Comments were solicited from several professional bodies to maximize clinical applicability before the recommendations were submitted for publication. The resulting document is intended to provide clinical guidelines for management of IMHA in dogs. These guidelines should be implemented pragmatically, with consideration of animal, owner, and veterinary factors that may vary among cases. [ABSTRACT FROM AUTHOR]

Immune‐mediated hemolytic anemia (IMHA) is an important cause of morbidity and mortality in dogs. IMHA also occurs in cats, although less commonly. IMHA is considered secondary when it can be attributed to an underlying disease, and as primary (idiopathic) if no cause is found. Eliminating diseases that cause IMHA may attenuate or stop immune‐mediated erythrocyte destruction, and adverse consequences of long‐term immunosuppressive treatment can be avoided. Infections, cancer, drugs, vaccines, and inflammatory processes may be underlying causes of IMHA. Evidence for these comorbidities has not been systematically evaluated, rendering evidence‐based decisions difficult. We identified and extracted data from studies published in the veterinary literature and developed a novel tool for evaluation of evidence quality, using it to assess study design, diagnostic criteria for IMHA, comorbidities, and causality. Succinct evidence summary statements were written, along with screening recommendations. Statements were refined by conducting 3 iterations of Delphi review with panel and task force members. Commentary was solicited from several professional bodies to maximize clinical applicability before the recommendations were submitted. The resulting document is intended to provide clinical guidelines for diagnosis of, and underlying disease screening for, IMHA in dogs and cats. These should be implemented with consideration of animal, owner, and geographical factors. [ABSTRACT FROM AUTHOR]

Background: A method of quantifying clinical bleeding in dogs with immune thrombocytopenia (ITP) is needed because ITP patients have variable bleeding tendencies that inconsistently correlate with platelet count. A scoring system will facilitate patient comparisons and allow stratification based on bleeding severity in clinical trials. Hypothesis/Objectives: To develop and evaluate a bleeding assessment tool for dogs, and a training course for improving its consistent implementation. Animals: Client-owned dogs (n=61) with platelet counts <50,000/μL; 34 classified as primary ITP, 17 as secondary ITP, and 10 as non-ITP. Methods: A novel bleeding assessment tool, DOGiBAT, comprising bleeding grades from 0 (none) to 2 (severe) at 9 anatomic sites, was developed. Clinicians and technicians completed a training course and quiz before scoring thrombocytopenic patients. The training course was assessed by randomizing student volunteers to take the quiz with or without prior training. A logistic regression model assessed the association between training and quiz performance. The correlation of DOGi- BAT score with platelet count and outcome measures was assessed in the thrombocytopenic dogs. Results: Clinicians and technicians consistently applied the DOGiBAT, correctly scoring all quiz cases. The odds of trained students answering correctly were higher than those of untrained students (P<.0001). In clinical cases, DOGiBAT score and platelet count were inversely correlated (rs=20.527, P<.0001), and DOGiBAT directly correlated with transfusion requirements (rs=0.512, P<.0001) and hospitalization duration (rs=0.35, P=.006). Conclusions and Clinical Importance: The DOGiBAT and assessment quiz are simple tools to standardize evaluation of bleeding severity. With further validation, the DOGiBAT may provide a clinically relevant metric to characterize ITP severity and monitor response in treatment trials. [ABSTRACT FROM AUTHOR]

Background: Platelet function testing may be warranted to assess response to aspirin and clopidogrel. Hypothesis/Objectives: To evaluate the effects of aspirin, clopidogrel, or combination therapy using 3 platelet function tests: Multiplate Analyzer (MP), Platelet Function Analyzer‐200 (PFA), and Plateletworks (PW). Animals: Six healthy laboratory Beagles. Methods: Randomized double‐blind placebo‐controlled study (crossover design). Dogs were given aspirin 1 mg/kg, clopidogrel 2 mg/kg, or combination therapy for 1 week each, with a washout period of 2 weeks. Platelet function was assessed on days 0 and 7 of each phase using MP (adenosine diphosphate [ADP], arachidonic acid [AA], collagen [COL] agonists), PFA (P2Y, COL‐ADP [CADP], COL‐Epinephrine [CEPI] cartridges), and PW (ADP, AA, COL agonists). Platelet counts were obtained with impedance and optical counters. Results: For MP, mean aggregation was decreased for COL and AA with combination therapy and for ADP with all treatments. For PFA, mean CT was increased for the CEPI cartridge with aspirin; and for the P2Y and CADP cartridges with clopidogrel or combination therapy. More dogs receiving clopidogrel showed an increase in PFA CT using the P2Y than the CADP cartridge. For PW, mean aggregation was decreased for AA with all treatments; for ADP with clopidogrel or combination therapy; and for COL with clopidogrel. The PW results with the 2 hematology counters showed almost perfect agreement. Conclusion and Clinical Importance: All platelet function tests detected treatment effects in some dogs and may have utility for monitoring therapy. [ABSTRACT FROM AUTHOR]

Background: Antiplatelet medications are increasingly used in dogs. Remote analysis of platelet activity is challenging, limiting assessment of antiplatelet drug efficacy. Hypothesis/Objectives: To evaluate a method used in humans for stimulation and remote analysis of canine platelet activity. Animals: Forty‐five dogs of various ages without a coagulopathy or thrombocytopenia. Six were receiving antiplatelet medication. Methods: Prospective observational study. Platelets were stimulated with combinations of arachidonic acid (AA) and epinephrine (Epi) or adenosine diphosphate (ADP) and the thromboxane A2‐mimetic U46619 (U4). PAMFix was added to the blood samples to facilitate delayed analysis of platelet activity. Activity was assessed by flow cytometric measurement of surface P‐selectin (CD62P) expression. Results: Canine platelets could be stimulated with both AA/Epi and ADP/U4. The levels of P‐selectin were significantly greater than paired, unstimulated samples (P < 0.001). Inhibition of P‐selectin expression occurred after this stimulation by adding antiplatelet drugs in vitro. The efficacy of antiplatelet drugs in samples from treated dogs was also measurable ex vivo using this method. Delayed analysis of platelet activity at time points up to 22 days demonstrated excellent correlation between respective mf values at each time point (r2 = 0.92, P < 0.0001). Conclusions and Clinical Importance: This study evaluated a new method to remotely assess canine platelet activity. It shows that PAMFix can be used for this purpose. This provides opportunities to interrogate the inhibitory action of antiplatelet drugs in clinical settings. [ABSTRACT FROM AUTHOR]

Omeprazole is used concurrently with clopidogrel to reduce gastrointestinal adverse effects. In humans, the concurrent use of these two drugs can reduce the antiplatelet efficacy of clopidogrel. Our objective was to determine the effects of omeprazole and clopidogrel on platelet function in healthy dogs. A crossover study utilized turbidimetric aggregometry (ADP and collagen) and the PFA-100® with the collagen/ADP cartridge to evaluate platelet function in eight healthy dogs during the administration of clopidogrel (1 mg/kg/24 h p.o.), omeprazole (1 mg/kg/24 h p.o.), and a combination of clopidogrel and omeprazole. Drug metabolite concentrations were also measured. Compared to pretreatment, on Days 3 and 5, with ADP as the agonist, there was a significant decrease in maximum amplitude on aggregometry for both clopidogrel and clopidogrel/omeprazole groups. The following revealed no significant differences between clopidogrel and clopidogrel/omeprazole groups when compared on Days 3 and 5: maximum amplitude on aggregometry with ADP or collagen agonists, and PFA-100® closure times. When compared to the clopidogrel group, clopidogrel metabolite concentrations in the clopidogrel/omeprazole group were significantly higher on Days 3 and 5. The concurrent administration of omeprazole and clopidogrel in healthy dogs was associated with an increase in the plasma concentration of an inactive metabolite of clopidogrel, but does not significantly alter the antiplatelet effects of clopidogrel. [ABSTRACT FROM AUTHOR]

Objective To clinically characterize a group of thrombocytopenic dogs that received cryopreserved platelet concentrate (cPC) transfusion, assess efficacy of cPC treatment in improving patient outcome, and compare treated dogs to a control population of thrombocytopenic dogs that did not receive cPC transfusions. Design Retrospective study. Setting University teaching hospital. Animals Eighty-six client-owned dogs (43 in treatment group, 43 in control group). Interventions None. Measurements and Main Results Medical records of thrombocytopenic dogs that received cPC transfusions and those of thrombocytopenic dogs that did not receive cPC (control population) from January 2007 through March 2013 were reviewed. Dogs receiving cPC were statistically more likely than controls to have a platelet trigger for cPC transfusion ( P = 0.01), lower platelet count ( P = 0.009) and hematocrit at presentation ( P = 0.001), and lower hematocrit after cPC ( P = 0.02). Although there was a statistically significant increase in platelet count from pre- to post-cPC transfusion ( P = 0.002), cPC was not found to be effective in improving clinical bleeding or increasing survival compared to the control group. No other characteristics were statistically different between groups. No dogs receiving cPC had an acute transfusion reaction during hospitalization. Conclusions In the population described in this study, cPC was not found to increase survival, but was well tolerated. Controlled, prospective studies are necessary to determine indications for and efficacy of cPC transfusions. [ABSTRACT FROM AUTHOR]

Background: Immune thrombocytopenia (ITP) in dogs is analogous to that in humans. Romiplostim, a novel thrombopoietin receptor (TPO-R) agonist, is currently used for the treatment of refractory ITP in humans, but not in dogs. Here, we describe the response to romiplostim in five dogs with refractory ITP. Five dogs with severe and refractory ITP (three primary and two secondary) received romiplostim subcutaneously. Four dogs were administered 3–5 μg/kg and one dog received 10–13 μg/kg body weight once weekly. Results: Romiplostim was well-tolerated and administration was associated with an increase in platelet counts in all five dogs. Four of the five dogs entered remission and relapses were not observed over a follow-up period of 3–10 months. Conclusions: Romiplostim is effective in the treatment of ITP in dogs at least as well as in humans. This finding may help to develop and use new therapeutics for ITP in dogs and humans. [ABSTRACT FROM AUTHOR]

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Despite limited information available on new immunosuppressive drugs in veterinary medicine, they are increasingly used by veterinarians for management of immune-mediated disease in dogs and cats. This article aims to summarise the information available for use of mycophenolate, leflunomide and budesonide in dogs using an evidence-based framework, to assist the veterinary practitioner in making therapeutic decisions. [ABSTRACT FROM AUTHOR]

Standard therapy forms the basic foundation for care of dogs with glomerular disease, as it is herein recommended for use in all affected animals regardless of causation of the disease. Consensus recommendations target the evaluation and management of proteinuria, inhibition of the renin-angiotensin-aldosterone system, modification in dietary intake with special consideration for those nutrients with renal effects, diagnosis and treatment of systemic hypertension, and evaluation and management of body fluid volume status in dogs with glomerular disease. [ABSTRACT FROM AUTHOR]