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.

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.

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.

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.

Pulmonary hypertension (PH) is the persistent abnormal increase in pulmonary artery (PA) pressure and in dogs is usually secondary to congenital disease causing pulmonary over circulation, chronic respiratory disease and elevated left atrial pressure. Sildenafil (SF) is a phosphodiesterase (PDE) V inhibitor that causes pulmonary artery (PA) vasodilation by increasing pulmonary vascular concentrations of cyclic guanosine monophosphate which subsequently increases the activity of endogenous nitric oxide. Pimobendan (PB) is a PDE III inhibitor with calcium sensitizing effects thereby exerting positive inotropy and vasodilation. The purpose of this retrospective study was to evaluate the long-term survival of dogs with severe PH treated with SF and PB compared to SF alone. The use of PB in combination with SF did not result in a statistically significant increase in survival times in dogs with pulmonary hypertension secondary to chronic respiratory disease compared to SF alone.

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.

OBJECTIVETo 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).DESIGNRetrospective case-controlled study.SETTINGTwo private practice referral hospitals.ANIMALSClient-owned dogs with RA masses and PE identified echocardiographically over a 3-year period.INTERVENTIONSNone.MEASUREMENTS AND MAIN RESULTSThere 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).CONCLUSIONSThis 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.

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.

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.

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.

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.

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.

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.

OBJECTIVE To evaluate the hand hygiene (HH) practices among veterinary technicians (VT) and veterinary support staff (VSS) in small animal private practice. METHODS This was a prospective questionnaire-based study involving 182 VT and VSS from 18 small animal hospitals in the USA. Questions asked included gender, number of animals handled per work shift, frequency of hand washing, reason for not washing more frequently, most common available hand washing agent, education regarding the importance of HH and frequency of ring wearing. RESULTS Less than half of the respondents [76 of 182 (41·7%)] reported washing their hands regularly between handling patients and 154 of 182 (85·6%) believed they should have washed more frequently. The most commonly employed HH agent was hand soap [154 of 182 (84·6%)] and the most common reason cited for not washing more frequently was being too busy [132 of 182 (72·5%)]. Only 96 of 182 (52·7%) respondents were educated by doctors at their hospital regarding the importance of HH. CLINICAL SIGNIFICANCE The HH practices among VT and VSS in small animal private practice is poor. Hand soap was the most commonly employed agent among respondents in this study. Education of VT and VSS regarding the importance of HH requires improvement.

OBJECTIVE To review the therapeutic options for immune-mediated thrombocytopenia (IMT). DATA SOURCES Original research publications and review articles using the PubMed search engine for the phrases "immune-mediated thrombocytopenia" or "immune thrombocytopenic purpura" or "immune thormbocytopenia." VETERINARY AND HUMAN DATA SYNTHESIS: There are a number of therapeutic options for adult-onset immune thrombocytopenia in human medicine with demonstrated efficacy in clinical studies although corticosteroids and immunoglobulin therapy remain the first-line medical treatments. Thrombopoietin receptor agonist therapy and, to a lesser extent, rituximab have shown great promise in initial clinical trials and may become standard of care in human medicine for the management of IMT. Therapeutic options in veterinary medicine are less diverse and only vincristine and human intravenous immunoglobulin therapies have been evaluated in controlled clinical studies. CONCLUSIONS There are a number of therapeutic options in the management of IMT veterinary medicine, most of which have not been investigated in clinical studies. Further research is warranted to best identify the optimal treatment strategy for IMT in veterinary patients.

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.

OBJECTIVE:To identify and characterize the syndrome of immune-mediated hemolytic anemia (IMHA) with concurrent severe thrombocytopenia (<or=15.0 x 10(9) platelets/L; [15.0 x 10(3) platelets/microL]), and to evaluate prognostic factors, clinicopathologic findings, complications, treatment, outcome, and survival of dogs with this hematologic disorder.DESIGN:Retrospective, observational study.SETTING:Veterinary teaching hospital.ANIMALS:Twelve client-owned dogs with IMHA and severe thrombocytopenia (<or=15.0 x 10(9) platelets/L; [15.0 x 10(3) platelets/microL]), without evidence of overt disseminated intravascular coagulation.INTERVENTIONS:The following data were recorded and analyzed from the electronic medical record: signalment, history, concurrent diseases, clinical signs at presentation, clinicopathologic data, diagnostic testing, radiographic findings, treatment modalities, length of hospitalization, complications, and clinical outcome. All dogs were treated with immunosuppressive doses of corticosteroids.MEASUREMENTS AND MAIN RESULTS:Twelve dogs were identified with the diagnosis of IMHA and severe thrombocytopenia; of these, 9 (75%) survived, 3 (25%) were euthanized, and none died. Dogs that survived were significantly younger than nonsurvivors (P=0.03). There were no specific clinical signs or therapies associated with survival.CONCLUSIONS:Dogs in this study had a mortality rate similar to reported rates for dogs with either disease alone. Overall, younger dogs were more likely to survive. No association between different treatment modalities and overall survival was identified.

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.