Retrospective evaluation of leflunomide as an adjunctive therapy in dogs with non-associative immune-mediated thrombocytopenia: 20 cases (2008-2021).

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 >150×109/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 >150×109/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.

Effects of canine influenza infection and DA2PP vaccination on the development of platelet-associated immunoglobulins and platelet counts in dogs.

BACKGROUND: Immune thrombocytopenia (ITP) is commonly associated with platelet-associated immunoglobulins (PAIg). Demonstration of PAIg can help determine etiologies for thrombocytopenia. In humans, ITP and thrombocytopenia have been associated with various vaccinations and influenza infections, respectively. OBJECTIVES: We aimed to evaluate platelet counts and PAIg in research dogs with H3N2 and in research and client-owned dogs routinely vaccinated for distemper, adenovirus-2, parainfluenza, and parvovirus (DA2PP). The hypotheses were that H3N2 infection but not DA2PP vaccination would decrease platelet counts, and neither would result in the detection of PAIg. METHODS: Three pilot studies. Platelet counts and PAIg, measured by direct flow cytometry as %IgG, were evaluated in eight research Beagles following experimental infection with H3N2 (experiment 1), nine research Beagles vaccinated for DA2PP (experiment 2), and thirty client-owned dogs vaccinated for DA2PP (experiment 3). All animals were considered healthy at the start of the experiments. RESULTS: Transient, self-resolving decreases in platelet counts and increases in %IgG occurred following H3N2 infection, and one dog became thrombocytopenic and positive for PAIg. Following DA2PP vaccination, %IgG increased in research and client-owned dogs, but only one dog was considered positive for PAIg with a concurrent increase in platelet count. Mean PAIg increased from baseline in client-owned dogs following vaccination. CONCLUSIONS: Transient PAIg and thrombocytopenia can occur following H3N2 infection, while routine vaccination for DA2PP in this group of dogs was not associated with the development of thrombocytopenia or clinically relevant formation of PAIg.

Use of human intravenous immunoglobulin for the treatment of 12 dogs with newly diagnosed malignant disease and presumed secondary immune-mediated thrombocytopenia.

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.

A prospective cohort study to identify clinical diagnostic and prognostic markers of primary immune thrombocytopenia in dogs.

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.

Clinical and Clinicopathologic Discriminators Between Canine Acute Monocytic Ehrlichiosis and Primary Immune Thrombocytopenia.

Acute canine monocytic ehrlichiosis due to Ehrlichia canis (aCME), and primary immune thrombocytopenia (pITP) are major differentials for dogs presented with thrombocytopenia, and the two diseases may clinically overlap. The aim of this study was to compare dogs diagnosed with naturally occurring aCME and pITP, to establish potentially useful clinical and clinicopathologic discriminators. A clinical record-based retrospective study was performed in 35 dogs diagnosed with aCME and 29 dogs with pITP. Dogs with aCME were significantly younger, and were more likely to experience depression or lethargy, anorexia, body weight loss, fever, lymphadenomegaly, tick infestation, and ocular discharge on admission, compared to dogs with pITP. In contrast, dogs with pITP presented more frequently with overt bleeding and had a significantly higher bleeding score compared to dogs with aCME. Dogs with aCME were more likely to be anemic and hypoalbuminemic on presentation compared to dogs with pITP. Dogs with pITP had higher white blood cell and neutrophil counts as well as lower platelet counts than dogs with aCME and were more likely to present with leukocytosis, neutrophilia and monocytosis. These clinical, hematological, and biochemical findings may be helpful discriminators between aCME and pITP, on the understanding that they will be interpreted in the context of disease-specific testing.

Investigation of single-nucleotide polymorphisms in the NR3C1a glucocorticoid receptor gene in Cocker Spaniels with primary immune thrombocytopenia.

BACKGROUND: In dogs, 6 single-nucleotide polymorphisms (SNPs) have been described in the glucocorticoid receptor gene NR3C1a, 2 of which were nonsynonymous SNPs in exons 2 and 8. The clinical importance of these SNPs is unknown. OBJECTIVES: To investigate whether SNPs in NR3C1a are associated with clinical outcome in Cocker Spaniels with primary immune thrombocytopenia (pITP). ANIMALS: Twenty-four Cocker Spaniels with pITP presented to a referral center. Dogs were classified as slow (n = 11) or fast responders (n = 12) based on time required after initiating glucocorticoid treatment to achieve a platelet count >70 000/µL. METHODS: Deoxyribonucleic acid was extracted from stored blood samples before amplification by PCR and sequencing of exons 2 and 8 of NR3C1a. Associations between genotype and clinical response variables were investigated. RESULTS: Neither previously identified nonsynonymous SNPs were identified. The synonymous SNP NR3C1a:c.798C>T in exon 2 was found at an increased prevalence compared to a previous report. No difference was found in prevalence of any genotype at NR3C1a:c.798C>T between fast and slow responders (P = .70). CONCLUSIONS AND CLINICAL IMPORTANCE: None of the previously reported nonsynonymous SNPs in exons 2 and 8 of the NR3C1a gene were detected in our cohort of Cocker Spaniels with pITP. The synonymous SNP NR3C1a:c.798C>T in exon 2 was reported at a higher frequency than previously, but was not associated with outcome measures that estimated responsiveness to glucocorticoids.

Preliminary evaluation of a flow cytometric assay with microsphere controls for the detection of platelet-bound antibodies in canine immune thrombocytopenia.

BACKGROUND: Canine immune thrombocytopenia (ITP) ranges from a mild to severe bleeding disorder, and platelet counts do not reliably predict clinical disease course. The detection of platelet autoantibodies may further define the disease phenotype, but variability in assay configurations and a lack of well-characterized controls limit the diagnostic utility of anti-platelet antibody assays. OBJECTIVES: We aimed to develop control reagents to facilitate the characterization of canine platelet surface-associated immunoglobulin (PSAIg) in flow cytometric assays. METHODS: Silica microspheres were coated with canine IgG and IgM to assess the reactivity of goat and rabbit origin anti-canine immunoglobulin reagents. They were also used as positive controls in the PSAIg assay. Preliminary assay evaluation and determination of sample stability used PRP isolated from seven healthy dogs and 26 dogs newly diagnosed with thrombocytopenia. RESULTS: Blood sample stability was established for up to a 48-hour storage time. The conjugated positive control microspheres demonstrated stable fluorescent labeling over a 2-year observation period. Rabbit and goat origin anti-dog IgM fluorescent antibody labels reacted nonspecifically with canine IgG. Rabbit origin anti-dog IgG antibody demonstrated greater class specificity for canine IgG than a goat origin antibody. Thrombocytopenic dogs had a broad range of membrane-bound immunoglobulin. Median PSAIgG for dogs with primary or secondary ITP (18.4%, 34.1%, respectively) were significantly higher than controls (3.8%, P < .05). CONCLUSIONS: The described assay reagents and procedures provide positive controls and allow consistent thresholding to define a positive test result, suitable for any flow cytometer. A rabbit anti-dog IgG fluorescent label demonstrated specificity for canine IgG and was useful for the detection of PSAIgG in thrombocytopenic dogs.

Immunomodulatory and immunosuppressive drug protocols in the treatment of canine primary immune thrombocytopenia, a scoping review.

Primary immune thrombocytopenia (ITP) is a cause of severe thrombocytopenia in dogs. Immunosuppressive corticosteroid drugs are frequently used in the management of ITP, but treatment failure may occur. Immunomodulatory and non-corticosteroid immunosuppressive drugs might improve outcomes from therapy either alone or in combination with corticosteroids. The objectives of this scoping review were (1) to evaluate the current evidence relating to immunomodulatory and immunosuppressive drug protocols in the treatment of canine ITP, and (2) to answer the clinical question, whether or not therapy with immunomodulatory or non-corticosteroid immunosuppressive drugs alone or in combination with corticosteroids could improve outcome, compared to therapy with corticosteroids alone. A literature search was performed in the electronic databases of Agricola, CAB Abstracts, Embase, Medline and Web of Science for publications in November 2019 and again February 1, 2021. Selection criteria were relatively strict and included peer-reviewed research papers reporting outcome measures from immunomodulatory and immunosuppressive drug protocols in the treatment of canine ITP with a pre-therapeutic mean or median platelet count < 50,000/µL as a strict criterion for inclusion. Studies were evaluated if they had an appropriate diagnostic work up to exclude underlying conditions. Outcome measures and adverse events were compared between drug protocols both within studies and between studies. The search identified 456 studies, with six studies being eligible for inclusion. The studies were mostly case series while two were randomized controlled trials. Level of evidence varied with an overall uncertain subject enrollment, small groups, inadequate description and variable use of drug protocols or outcome measures. For outcomes such as platelet recovery time and duration of hospitalization, an improvement was observed using adjunctive therapy (human intravenous immunoglobulin) compared to therapy with corticosteroids alone. For outcomes of complete platelet recovery time, survival (6-month), mortality and relapse, no improvement was observed using adjunctive drugs compared to corticosteroids alone. Specifically, therapy with mycophenolate mofetil alone and adjunctive azathioprine were associated with more severe adverse events compared to other drug protocols. Evidence relating to immunomodulatory and immunosuppressive drug protocols in the treatment of canine ITP was of variable quality. Future larger case-controlled trials are required for determination of optimal treatment protocols in canine ITP.

Romiplostim as Adjunctive Treatment of Refractory Amegakaryocytic Immune Thrombocytopenia in a Dog.

A 9-year-old, intact male, mixed-breed dog was admitted with a 3-day history of severe thrombocytopenia and bleeding diathesis. Physical examination revealed mucosal and cutaneous petechiae and ecchymoses, melena, and gross hematuria. Clinicopathologic evaluation indicated severe thrombocytopenia, anemia, and panhypoproteinemia. Serology for common endemic vector-borne pathogens was negative and thoracic and abdominal imaging was unremarkable. Bone marrow aspiration cytology revealed aplasia of the megakaryocytic lineage, in the context of a mildly hypoplastic myeloid and a normal erythroid series. A diagnosis of presumptive primary amegakaryocytic immune thrombocytopenia (ITP) was established. Treatment with vincristine, prednisolone, and mycophenolate mofetil along with several whole blood transfusions failed to achieve clinical and clinicopathologic remission. As an adjunct treatment, romiplostim was administered at a cumulative dose of 15 µg/kg, subcutaneously, in 2 sessions, 1 week apart, and complete clinical and hematological remission was noted 8 days postinitiation of romiplostim. Thirty-eight months later, the dog remains clinically healthy with no evidence of hematological relapse. Romiplostim could be a promising adjunctive treatment option in dogs with refractory ITP.

Application of therapeutic plasma exchange in dogs with immune-mediated thrombocytopenia.

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.

Detection and dynamics of anti-platelet antibodies in thrombocytopenic dogs with and without idiopathic immune thrombocytopenia.

BACKGROUND: Antiplatelet antibodies are detected in multiple diseases including primary immune thrombocytopenia (ITP). Dynamics of how these antibodies change over time in ITP is unknown in dogs. HYPOTHESIS/OBJECTIVES: Antiplatelet antibodies (APA) will be detected in thrombocytopenic dogs with multiple etiologies and dynamics of APA in dogs with ITP can be used to evaluate response to treatment and relapse. Determine APA at the time of diagnosis in thrombocytopenic dogs and serially in primary ITP dogs. ANIMALS: Seventy-nine thrombocytopenic dogs and 28 primary ITP dogs. METHODS: Direct flow cytometry was performed in thrombocytopenic dogs at initial evaluation and serially in suspected primary ITP dogs. In primary ITP dogs, a 2-tailed Fisher's exact test was performed comparing survival to discharge between dogs with and without melena and to relate response to treatment and relapse to changes in APA and platelet count (repeated measures analysis, Spearman correlation). RESULTS: Twenty percent (16/79) of thrombocytopenic non-ITP dogs with infectious, neoplastic, or other diseases and all primary ITP dogs were positive for APA. Melena at initial evaluation was associated with decreased survival to discharge (odds ratio 0.06; P = .01). Persistence of APA was not associated with response to treatment, but recurrence of antibodies was associated with relapse (odds ratio 205.0; P < .01). There was no difference in percentage of APA or platelet count at initial diagnosis between dogs that did or did not respond to treatment. CONCLUSIONS AND CLINICAL IMPORTANCE: Serial monitoring of APA in dogs with primary ITP appeared beneficial for determining relapse of disease.

Long-term outcome of primary immune-mediated thrombocytopenia in dogs.

OBJECTIVES: To determine the incidence of relapse after discharge from the hospital in dogs with a diagnosis of presumed primary immune-mediated thrombocytopenia, risk factors associated with relapse and whether or not indefinite use of immunosuppressive medication influences risk of relapse. MATERIALS AND METHODS: Medical records from August 2007 through July 2016 were reviewed to identify dogs with a diagnosis of presumed primary immune-mediated thrombocytopenia. Data collection included signalment, initial diagnostic tests, treatment, incidence of relapse, survival duration and follow-up testing. RESULTS: A total of 45 dogs were diagnosed, treated and monitored for at least one year for presumed primary immune-mediated thrombocytopenia. 89∙6% of patients survived to discharge and 31% of those experienced a relapse following discharge. The median time from diagnosis to relapse was 79 days. Of dogs that experienced a relapse, 50% had at least one further relapse. There was no difference in age, body weight, gender, breed, platelet count at presentation, nadir packed cell volume during hospitalisation, incidence of melaena or initial treatment between the relapsing and non-relapsing groups. In the relapsing group, time to platelet recovery was significantly longer and these patients were more likely to have received a blood transfusion. CLINICAL SIGNIFICANCE: This study does not provide evidence to support the use of long-term immunosuppressive medications to prevent relapse. However, the data suggest that patients with more severe disease at the time of diagnosis or that have already experienced a relapse should be monitored more closely.

Development and implementation of a novel immune thrombocytopenia bleeding score for dogs.

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 DOGiBAT 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 = -0.527, 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.

Urban environment: a risk factor for canine immune-mediated disease?

OBJECTIVES: To investigate whether dogs living in urban areas are more likely to develop immune-mediated disease than those in rural areas. MATERIALS AND METHODS: A case-control study comparing the prevalence of urban home location between dogs with immune-mediated disease and matched controls. Dogs diagnosed with immune-mediated haemolytic anaemia, immune-mediated thrombocytopenia, immune-mediated polyarthritis or meningoencephalomyelitis of unknown origin were identified by case record searches. Breed-matched dogs presenting to the same hospital during the same year as cases were randomly selected as controls. Home locations were classified as rural or urban using the population density of the relevant census tract and conditional logistic regression was used to examine association between home location and immune-mediated disease. RESULTS: In the 137 cases and 137 breed-matched controls, the odds ratio for any immune-mediated disease for dogs living in urban (versus rural) areas was 0·94 (95% confidence interval 0·58 to 1·55, P=0·80). Odds ratios for development of immune-mediated haematological diseases, immune-mediated polyarthritis or meningoencephalomyelitis of unknown origin were also not significantly different from the null value. Multivariable analysis including age, gender and season of presentation did not suggest confounding of effect of home location by these additional variables. CLINICAL SIGNIFICANCE: This study does not support an association between urban environment and immune-mediated disease in dogs.

Systemic neosporosis in a dog treated for immune-mediated thrombocytopenia and hemolytic anemia.

A 4-year-old male Toy Poodle was presented to the Small Animal Veterinary Hospital of the Faculty of Veterinary Medicine of the Autonomous University of Mexico (FMVZ, UNAM) because of depression, lethargy, and hemorrhages involving several areas of the skin and around the eyes. Hematology data and a bone marrow analysis suggested hemolytic anemia and immune-mediated thrombocytopenia. The dog was treated with prednisone, and after one month the hematology variables improved. However, the dog's clinical condition inexplicably worsened and it was euthanized. On necropsy, there were no relevant findings. However, in histology, multifocal lymphoplasmacytic and histiocytic meningoencephalitis and necrosis, and a protozoan cyst in the cerebellum were identified. In addition, moderate multifocal lymphoplasmacytic and necrotizing pancreatitis, hepatitis, myocarditis, and diffuse lymphoplasmacytic enteritis were observed. Immunohistochemistry of the cerebellum, liver, pancreas, and intestine with a specific antibody against Neospora caninum confirmed the diagnosis of systemic neosporosis. The systemic neosporosis in this dog was most likely caused by reactivation of latent parasites due to prednisone administration during the one month of treatment. It should be kept in mind that in dogs being treated with immunosuppressants for immune-mediated conditions, opportunistic parasites, such as Toxoplasma gondii and N caninum, can be reactivated from a latent state, as it probably happened in the present case.

Application of vincristine-loaded platelet therapy in three dogs with refractory immune-mediated thrombocytopenia.

Three dogs presented with refractory immune-mediated thrombocytopenia (IMT). All patients failed to respond to prednisone, which is considered a mainstay of immunosuppressive therapy. Vincristine-loaded platelets (VLPs), which act selectively on mononuclear phagocytes,were introduced. After the VLPs were transfused, two dogs responded quickly with improved clinical signs while the third dog with recurrent IMT was euthanized due to its deteriorating condition. This case report describes the efficacy of VLP therapy in refractory IMT patients.

Canine pemphigus foliaceus with concurrent immune-mediated thrombocytopenia.

A 3 yr old wirehaired fox terrier was presented to his primary care veterinarian with fever, thrombocytopenia, and generalized crusting dermatitis. The skin lesion had progressed for at least 18 days, and thrombocytopenia had developed 3 days before presentation. Histopathology and direct immunofluorescence studies of the skin were consistent with pemphigus foliaceus (PF). Immunofluorescence revealed immunoglobulin G deposition around the keratinocytes in the stratum spinosum. A diagnosis of immune-mediated thrombocytopenia (IMT) was confirmed by the presence of platelet surface-associated immunoglobulin using flow cytometry. Systemic immunosuppressive therapy with cyclosporine and azathioprine was effective, and the dog survived for >2 years from the initial presentation. IMT is rarely associated with PF. This appears to be the first detailed report of a definitive diagnosis of concurrent PF and IMT in a dog. The authors' findings indicate that canine PF could be complicated by hematologic immune-mediated diseases such as IMT.

Lameness associated with tarsal haemarthrosis as the sole clinical sign of idiopathic immune-mediated thrombocytopenia in a dog.

A four-year-old, male Cocker Spaniel was presented for investigation of pelvic limb stiffness. There was palpable effusion of both tarsi, and analysis of synovial fluid from these joints indicated previous haemorrhage. After further investigation a diagnosis of idiopathic immune-mediated thrombocytopenia was made. The dog responded to treatment with prednisolone and azathioprine. To the authors' knowledge, this is the first reported case of confirmed haemarthrosis as the sole presenting clinical sign for canine idiopathic immune-mediated thrombocytopenia.

Platelet volume and plateletcrit in dogs with presumed primary immune-mediated thrombocytopenia.

BACKGROUND: Mean platelet volume (MPV) and plateletcrit (PCT) are indices used in evaluating immune-mediated thrombocytopenia (IMT) in humans and in dogs with congenital macrothrombocytopenia. These indices may provide clinically valuable information in acquired thrombocytopenia. HYPOTHESIS/OBJECTIVES: Dogs with presumed primary IMT will have increased MPV, and therefore platelet mass (PCT) will increase faster than platelet count (PLT) during recovery. ANIMALS: Forty-nine dogs with automated PLT < 30,000/µL because of presumed primary IMT and hematocrit (HCT), PCT, MPV, and platelet distribution width determined from the same complete blood count (CBC), and 46 healthy controls. METHODS: Case-control retrospective study; PLT, PCT, MPV, and platelet distribution width (PDW) were recorded from CBCs from 49 dogs, with 45 having data collected on the day of presentation. Fifteen were confirmed to have attained a PLT ≥ 75,000/µL on at least 1 CBC within 15 days after admission. The PCT equivalent to a PLT of 75,000/µL (assuming an average MPV) was calculated for comparison with PLT in terms of time to achieve a threshold of platelet mass by the 2 measures. RESULTS: Mean platelet volume was higher in IMT dogs (17.3 fl) than the reference population (10.5 fl) (P < .0001). The PDW was not significantly different among the groups. The median time for PCT to reach threshold in confirmed responders was faster (3 days) compared with PLT (4 days). CONCLUSIONS AND CLINICAL IMPORTANCE: Immune-mediated thrombocytopenia is characterized by increased MPV. Time to achieve a threshold PCT tended to be shorter than PLT, suggesting that PCT may be a useful platelet parameter for monitoring dogs with IMT.