Platelet size,platelet surface-associated IgG,and reticulated platelets in dogs with immune-mediated thrombocytopenia

Abstract: Immune-mediated thrombocytopenia (IMT) is a disorder in which bound IgG on the surface of platelets results in platelet removal and alterations in mean platelet volume. Using flow cytometry, alterations in platelet size, platelet surface-associated IgG (PSAIgG), and numbers of reticulated platelets were determined in 13 dogs with primary IMT and 4 dogs with secondary IMT induced by experimental infection with Babesia gibsoni . Effects of sample age on platelet parameters also were determined, using samples from 20 dogs with normal platelet counts analyzed within 4 hours and after 24, 48, and 72 hours of storage in EDTA. No significant changes in platelet count, platelet size, or reticulated platelet percentage were observed in samples assayed within 4 and 24 hours of blood collection; whereas PSAIgG values increased 3 to 7 fold in samples stored for 24–72 hours. Using reference values for freshly collected or 24-hour-old samples, 10 of 13 (77%) dogs with primary IMT and all B gibsoni-inf ected dogs had increased PSAIgG levels. In 12 (75%) of the 16 dogs with thrombocytopenia the percentage of reticulated platelets was increased; however, absolute numbers of reticulated platelets were within reference values. Moreover, PSAIgG level and the percentage of reticulated platelets were not always increased concurrently in dogs with primary and secondary IMT. Platelet microparticles were detected in all B gibsoni-infected dogs, 8 of 13 (62%) dogs with primary IMT, and transiently in a dog that responded to immunosuppressive treatment. The results of this study indicate that sample age and time of sampling during disease affect interpretation of platelet parameters in dogs with IMT.     

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 withimproved clinical signs while the third dogwith recurrent IMT was euthanized due to its deteriorating condition. This case report describesthe efficacy of VLP therapy in refractory IMT patients.     

Treatment of severe immune-mediated thrombocytopenia with human IV immunoglobulin in 5 dogs

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.     

Concurrent immune-mediated haemolytic anaemia and severe thrombocytopenia in 21 dogs

The medical records of 21 dogs with concurrent immune-mediated haemolytic anaemia (imha) and severe thrombocytopenia (defined as an automated platelet count of less than 50x10(9)/l, confirmed by the examination of a blood smear) were reviewed. Their mean (sd) age was 5.8 (2.5) years. When compared with the 24,759 dogs in the hospital population for the same period Airedale terriers and dobermanns appeared to be over-represented with odds ratios of 22.5 (95 per cent confidence interval [ci] 5.2 to 97.9) and 7.6 (95 per cent ci 1.8 to 32.7) respectively. The median duration of the dogs' clinical signs was seven days, with a range from one to 17 days. Eleven of the dogs had a history of a tendency to bleed, and 15 had evidence of bleeding when examined. Twenty of the 21 dogs had been treated with glucocorticoids, nine with vincristine, and seven with azathioprine. Their median stay in hospital was four days, with a range from one to 17 days. The median period for which they survived after admission to hospital was five days, with a range from one to 558 days, and 16 of the 21 dogs had died or been euthanased within 30 days of their admission.     

Platelet aggregation in dogs experimentally infected with Rickettsia rickettsii

Platelet aggregation studies were performed on nine Beagle dogs experimentally infected with Rickettsia rickettsia. Platelets from dogs with Rocky Mountain spotted fever tended to be more aggregable than controls.     

Diagnosis of microthrombocytosis and immune-mediated thrombocytopenia in dogs with thrombocytopenia: 68 cases (1987-1989).

The mean platelet volume (MPV) was evaluated in 68 dogs with thrombocytopenia attributable to various causes. Platelet size was high or low in some dogs. The most clinically useful observation was that low MPV (microthrombocytosis) was a specific indicator of immune-mediated thrombocytopenia (IMT) in these thrombocytopenic dogs. All but one case of microthrombocytosis (MPV less than 5.4 fl) was found in dogs with IMT. Microthrombocytosis was detected in 17 of 31 dogs with IMT and appeared at the onset of the disease. Macrothrombocytosis (MPV greater than 9.4 fl) indicated active thrombopoiesis, but was not unique to any disease category. Macrothrombocytosis was detected in 18 of 31 dogs with IMT, 3 of 17 dogs with disseminated intravascular coagulation, and 3 of 9 dogs with primary bone-marrow disease.     

Primary immune-mediated thrombocytopenia in 30 dogs (1997-2003)

During a 6-year period, primary (idiopathic) immune-mediated thrombocytopenia was retrospectively evaluated in 30 dogs. Ages of the dogs ranged from 3 months to 10 years (median 4 years); female dogs were markedly overrepresented with 73%. Clinical examination revealed hemorrhages in 70% of the dogs. Platelet counts ranged from 0 to 111,000/microL (median 8000/microL); 77% of the dogs had platelet counts <30,000/microL. Seventeen dogs were anemic (hematocrit 9% to 36%; median 31%). Immunosuppressive therapy was performed in all but one dog. The recurrence rate of 19 dogs that were followed over an extended period (112 to 1684 days; median 340 days) was 26%. Twenty-nine (97%) dogs survived 14 days after initial presentation, and 27 (93%) dogs survived at least the following 15 to 1684 days (median 220 days).     

Epidemiologic survey of thrombocytopenia in dogs: a report on 987 cases

Thrombocytopenia was documented in 987 of 18,910 (5.2%) dogs admitted to North Carolina State University, College of Veterinary Medicine, Veterinary Teaching Hospital, between 1983 and 1989. Classifying thrombocytopenic dogs by etiologic groups revealed the following proportionate ratios: 5% (48/987) immune-mediated thrombocytopenia; 13% (130/987) neoplasia-associated thrombocytopenia; 23% (224/987) inflammatory/infectious thrombocytopenia; and 59% (585/987) miscellaneous thrombocytopenia. Dogs with immune-mediated thrombocytopenia had significantly (P < 0.05) lower platelet counts (mean 36,760 +/- 50,288 microliter) than dogs in the other three groups, and Doberman Pinschers were overrepresented in all groups except the immune-mediated thrombocytopenic group. We conclude that thrombocytopenia is a prevalent and potentially important diagnostic finding in a variety of disease states.     

Use of therapeutic plasmapheresis in a case of canine immune-mediated hemolytic anemia

Objective – To investigate the clinical application and potential utility of plasmapheresis in canine immune-mediated hemolytic anemia.
Case Summary – A 7-year-old spayed female Maltese diagnosed with immune-mediated hemolytic anemia was initially treated with prednisone, cyclosporine, and received multiple transfusions of packed RBC. Because of the progression of clinical signs despite traditional medical therapy, plasmapheresis was initiated. Plasma immunoglobulin G and immunoglobulin M levels were measured before, during, and after treatment to help determine if there had been a significant decrease in immunoglobulin levels with plasmapheresis. Plasmapheresis was successfully performed over a 2.5-hour period in this dog with minimal complications. Hypocalcemia was identified as a known complication of circuit anticoagulation, and was corrected through calcium supplementation. Post-plasmapheresis there was a decrease in immunoglobulin G and immunoglobulin M levels, and the patient showed clinical improvement. Following discharge the dog had no known complications of therapy, and had complete resolution of the anemia.
New or Unique Information Provided – Plasmapheresis was performed successfully with minimal complications. Because transfusion requirements appeared to be reduced, and the procedure was well tolerated, there may be a place for this modality in severe cases to act as a bridge until medical therapy takes full effect. Because of the cost of performing this therapy, and the potential requirement for multiple treatments, it should be reserved for selected patients.     

Use of human immunoglobulin in addition to glucocorticoids for the initial treatment of dogs with immune-mediated hemolytic anemia

Objective – To determine the utility of human intravenous immunoglobulin (hIVIG) for the initial treatment of canine immune-mediated hemolytic anemia (IMHA).
Design – Blinded, randomized, clinical trial.
Setting – Veterinary teaching hospital.
Animals – Twenty-eight, client-owned dogs with primary IMHA.
Interventions – At enrollment, after diagnosis of IMHA, dogs were randomly assigned to receive either hIVIG or placebo, in a blinded fashion. For the next 14 days, all dogs received glucocorticoids as the sole immunosuppressant agent. All dogs received low-molecular-weight heparin as an anticoagulant. D-dimer concentrations were evaluated at the beginning and end of the study protocol to monitor for thromboembolic complications.
Measurements and Main Results – Twenty-five of 28 dogs (89%) were discharged from the hospital. Thirteen of those received hIVIG and 12 received placebo. Twenty-four dogs (86%) were alive 14 days after enrollment, and of these 13 received hIVIG and 11 received placebo. D-dimer concentrations were elevated in 86% of all dogs at the time of diagnosis.
Conclusions – For initial treatment of dogs with IMHA, the addition of hIVIG to corticosteroid treatment did not improve initial response, nor did it shorten hospitalization.