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Immune Mediated thrombocytopenia (IMT)
Immune Mediated thrombocytopenia (IMT) is when there is reduction in platelets (thrombocytes) caused by body's own immune system at a faster rate than the bone marrow can produce them. Whether it is an inherited disease or not is questionable although it occurs more frequently in English Sheepdogs, poodles, German Shepherds and cocker spaniels and more frequently in females than males. Symptoms are weakness and lethargy and when the platelet count falls below 30,000 per cubic millimetre of blood bleeding such as nosebleeds and bruising...There could be other causes for this to happen that have to be ruled out before IMT is the diagnosis...

"Unfortunately, mortality rates of patients with IMT approach 50 percent: death is caused by severe blood loss, especially bleeding into the gastrointestinal tract, or bleeding into the brain...Corticosteroids are the cornerstone of treatment for dogs and cats with IMT: " Please click for full article from VEtCentric.


Immune-Mediated Hemolytic Anemia and Immune-Mediated Thrombocytopenia
By
Carol Norris, DVM, DACVIM, Clinician,
Veterinary Medical Teaching Hospital, School of Veterinary Medicine, University of California, Davis

Immune - mediated hemolytic anemia (IMHA) and immune- mediated thrombocytopenia (ITP) are diseases in which the body's own immune system attacks its red blood cells (IMHA) or platelets (ITP). Symptoms that develop are caused by a massive, often sudden, depletion of red blood cells or platelets. One of the major functions of red blood cells is to carry oxygen from the lungs to all other tissues in the body. When there are inadequate numbers of red blood cells (anemia) the body becomes starved for oxygen. As the pet owner, you may notice depression, listlessness, panting, loss of appetite, weakness or reluctance to exercise in your pet.
The major function of platelets is to help form blood clots to stop bleeding. Destruction of large number of platelets can result in pinpoint bleeding in the skin or gums or may appear as nosebleeds. Less commonly, blood can be seen in the stool, ( which takes on a black appearance if it is digested or a bright red appearance if it is not) or urine. Severe anemia can result from excessive bleeding. Occasionally, IMHA and ITP occur together.
IMHA and ITP are more commonly seen in dogs than cats. It is believed that cocker spaniels, toy and miniature poodles and Old English sheepdogs are breeds predisposed to develop IMHA. The latter two breeds and standard poodle are also at increased risk for developing ITP. Most affected dogs are middle-aged females. No breed or sex predilection is appreciated in cats. You should remember, however, that these conditions can develop in any dog or cat of any age, either sex, neutered or not. There is no scientific evidence that these diseases are caused by anything you feed your pet or where your pet lives.
Both IMHA and ITP can be classified as "primary" or "secondary". In primary disease, no underlying cause of the immune destruction can be found after an exhaustive clinical and laboratory evaluation. In comparison, secondary IMHA or ITP occurs when the immune system inadvertently destroys its own blood cells or platelets secondary to an immune attack directed against an underlying condition such as cancer, infection, a drug or toxin exposure. If an underlying condition is present, it is critical to attempt to correct that problem while simultaneously treating the immune disease. Treatment of IMHA and ITP relies on suppressing the immune system's attack against the red blood cells and platelets respectively. The medication most commonly prescribed to shut off the immune system is a steroid hormone called prednisone. Side effects of this drug in dogs include an increase in water intake and urination, an increase in appetite and panting: cats tend not to have significant side effects. Therapy must be continued until there is laboratory evidence that anemia has resolved and there is no ongoing destruction of red blood cells or platelets. This requires frequent recheck examinations to monitor the success of therapy. If the immune system has been adequately suppressed, the dosage of prednisone can be slowly tapered (often over a period of several months) and ultimately discontinued. Generally most veterinarians like to check a dog or cat immediately before each decrease in prednisone dose. These frequent rechecks are extremely important. If inadequate suppression of the immune system occurs, additional drugs such as cyclophosphamide, azathioprine, or cyclosproine may be tried. These drugs can have more severe side effects then prednisone, so it is important to talk to your veterinarian about the potential risks of each medication and what problems you need to look for. In some dogs and cats, the destruction of red blood cells or platelets is so severe that life-threatening anemia can occur. Blood transfusions may be necessary to stabilize these pets until the bone marrow can keep up with the demand for red blood cells and platelets and until the drugs suppressing the immune attack have had time to work.
Prognosis for both diseases is highly variable and depends on the underlying cause if one is present, complications related to the disease or drug therapy, and the response to treatment. Relapses can occur months to years after the initial episode. Overall, if there is no severe underlying illness or significant complications and if your pet responds to therapy, prognosis for both diseases is generally good. Permission is hereby granted to reproduce the Client Information Series in this publication in complete pages, with the copyright notice for instructional use and not for resale.
Copyright 2000 by W. B. Saunders Company. All rights reserved.

IMMUNE-MEDIATED THROMBOCYTOPENIA (Immune Destruction of Blood Platelets)
marvistavet-Immune Destruction of Blood Platelets
Immune-Mediated Thrombocytopenia (IMT)

Thrombocytopenia and Platelet problems by Dr.Mike=Vetinfo
Res Vet Sci. 1992 Jul;53(1):87-92. : Immune-mediated disease in the old English sheepdog.
Day MJ, Penhale WJ
. Division of Veterinary Biology, School of Veterinary Studies, Murdoch University, Australia.

Immunological data are reported from 19 cases of immune-mediated disease recorded in the old English sheepdog breed in Western Australia between 1978 and 1989. The conditions included autoimmune haemolytic anaemia (seven), idiopathic thrombocytopenia (one), Evans' syndrome (five), multiple myeloma (two), systemic lupus erythematosus (one), discoid lupus erythematosus (one) and hypothyroidism (two). The most consistent serological findings were raised serum IgG (60 per cent), depressed serum IgM (60 per cent) and the presence of multiple autoantibodies (anti-red blood cell 78 per cent, antinuclear antibody 44 per cent, rheumatoid factor 19 per cent). An underlying, breed-related disorder of immune regulation may account for these observations.

J Vet Intern Med. 2002 Sep-Oct;16(5):504-9.: Comment in: J Vet Intern Med. 2002 Sep-Oct;16(5):501-3.
Prognostic factors for mortality and thromboembolism in canine immune-mediated hemolytic anemia: a retrospective study of 72 dogs.
Carr AP, Panciera DL, Kidd L.
Small Animal Clinical Sciences, Western College of Veterinary Medicine, Saskatoon, SK, Canada.
endovet@juno.com

Medical records of 72 dogs diagnosed with immune-mediated hemolytic anemia (IMHA) were reviewed to find risk factors for the disease, for mortality, and for thromboembolism. Coagulation data of 32 patients were evaluated for mortality or thromboembolism risk factors. Cocker Spaniels were at increased risk for IMHA (P = .012). Timing of vaccination was not associated with development of IMHA. PCV ranged from 5 to 33%, with a mean of 16 +/- 5%. Autoagglutination was present in 42% of the dogs. Platelet counts (n = 60) varied from 3,000 to 793,000/microL (mean, 160,117 +/- 133,571; median, 144,000). Thrombocytopenia (platelet count, <200,000/microL) was present in 70% of the dogs, with severe thrombocytopenia (platelet count, <50,000/microL) being present in 22%. One-step prothrombin time (OSPT) was prolonged in 28% of the dogs tested, and activated partial thromboplastin time (APTT) was prolonged in 47% of the dogs tested. Fibrin(ogen) degradation products (FDPs) were detected in 16 of 28 dogs tested (57%). Disseminated intravascular coagulation (DIC) was diagnosed in 10 of 31 (32%) dogs and was suspected in 8 dogs. Thromboemboli were found in 20 of 25 dogs given postmortem examinations. Mortality rate was 58%. Thrombocytopenia (P = .008) and serum bilirubin concentration of >5 mg/dL (P = .015) were risk factors for mortality, and hypoalbuminemia approached significance (P = .053). Severe thrombocytopenia (P = .046), serum bilirubin concentration of >5 mg/dL (P = .038), and hypoalbuminemia (P = .016) were risk factors for thromboembolism. On evaluation of continuous data, decreased platelet count (P = .057), increased bilirubin (P = .062), and decreased albumin (P = .054) approached significance for decreased survival. A higher risk for thrombosis was found with increased alkaline phosphatase (ALKP) (P = .042), increased bilirubin (P = .047), and decreased albumin (P = .012).

J Am Anim Hosp Assoc. 2002 Mar-Apr;38(2):125-33. : Clinical signs, clinicopathological findings, etiology, and outcome associated with hemoptysis in dogs: 36 cases (1990-1999).
Bailiff NL, Norris CR.
Veterinary Medical Teaching Hospital, School of Veterinary Medicine, University of California, Davis 95616, USA.

Hemoptysis, the expectoration of blood or bloody mucus from the respiratory tract at or below the larynx, was retrospectively evaluated in 36 dogs. Cough, tachypnea, and dyspnea were common historical and physical examination signs. Anemia was documented in 11 dogs, but was severe in only one dog. Other clinicopathological findings reflected the underlying diseases. All thoracic radiographs obtained were abnormal; alveolar and interstitial patterns were most common. Diseases predisposing to hemoptysis included bacterial bronchopneumonia (n=7), neoplasia (n=5), trauma (n=5), immune-mediated thrombocytopenia (n=4), heartworm disease (n=4), rodenticide poisoning (n=3), lung-lobe torsion (n=1), left-sided congestive heart failure (n=1), pulmonary hypertension (n=1), and foreign-body pneumonia (n=1). Four additional dogs had more than one underlying disease process. Nine dogs were either euthanized or died in the hospital during the initial visit. While at least half of the 27 dogs discharged went on to completely recover, five dogs discharged were known to have either died or been euthanized as a result of their disease in <6 months.

: J Am Vet Med Assoc. 2002 Feb 15;220(4):477-81. : Comparison of platelet count recovery with use of vincristine and prednisone or prednisone alone for treatment for severe immune-mediated thrombocytopenia in dogs.
Rozanski EA, Callan MB, Hughes D, Sanders N, Giger U.
Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania, Philadelphia 19104-6010, USA.

OBJECTIVE: To evaluate the effect of prednisone alone, compared with a combination of prednisone and vincristine, on platelet counts in bleeding dogs with severe primary immune-mediated thrombocytopenia (IMT). DESIGN: Prospective case study. ANIMALS: 24 dogs with severe primary IMT PROCEDURE: All dogs received immunosuppressive doses of prednisone (1.5 to 2 mg/kg [0.7 to 0.9 mg/lb] of body weight, PO, q 12 h). In addition, 12 dogs received a single dose of vincristine (0.02 mg/kg [0.01 mg/lb], IV). Platelet count, transfusion requirement, and outcome were monitored. A response was defined as an increase in platelet count to > or = 40,000/microl. Dogs in the prednisone group that failed to respond received 1 dose of vincristine on day 7. RESULTS: Dogs that received prednisone and vincristine had a significantly faster increase in platelet count to > or = 40,000 platelets/microl than dogs that received prednisone alone (mean +/- SD, 4.9 +/- 1.1 vs 6.8 +/- 4.5 days, respectively). A similarly rapid response was observed in dogs that received vincristine on day 7 after treatment with prednisone alone failed. Furthermore, duration of hospitalization was reduced in the vincristine group, compared with the prednisone group (5.4 +/- 0.3 vs 7.3 +/- 0.5 days, respectively). No adverse effects attributable to vincristine were observed in any dog. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of combined vincristine and prednisone is associated with more rapid increase in platelet numbers and shortened duration of hospitalization in dogs with IMT, compared with use of prednisone alone. Early use of vincristine seems warranted in dogs with severe primary IMT.

Vet Clin Pathol. 2001;30(3):141-149. : Platelet size, platelet surface-associated IgG, and reticulated platelets in dogs with immune-mediated thrombocytopenia.
Wilkerson MJ, Shuman W, Swist S, Harkin K, Meinkoth J, Kocan AA.
Department of Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506.
wilkersn@vet.ksu.edu

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-infected 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.

J Small Anim Pract. 1999 May;40(5):227-32. : Immune-mediated thrombocytopenia associated with Angiostrongylus vasorum infection in a dog.
Gould SM, McInnes EL.
Department of Clinical Veterinary Medicine, Queen's Veterinary School Hospital, Cambridge

A three-year-old weimaraner was presented with lethargy, anorexia, neck pain and a soft fluctuant swelling in the thoracic inlet. A cough had been noted previously. Clinical examination revealed tachycardia, tachypnoea, pallor and a large subcutaneous swelling, with bruising, suggestive of a haematoma in the thoracic inlet. Thoracic radiographs revealed a cranial mediastinal mass which had the ultrasonographic appearance of fluid, and there was also a marked generalised interstitial lung pattern. Routine haematology revealed severe anaemia and thrombocytopenia, although coagulation tests were within normal limits. A diagnosis of immune-mediated thrombocytopenia was however made on the basis of a positive antiplatelet antibody test and a rapid response to prednisolone therapy. Furthermore, a tentative diagnosis of Angiostrongylus vasorum infection was suggested on the basis of clinical and radiographic findings, although no lungworm larvae were identified on faecal analysis. Despite initiating treatment with fenbendazole, the dog died suddenly. Postmortem examination revealed myocarditis, thrombosing arteritis, pneumonia and chronic membranoproliferative glomerulonephritis associated with A vasorum infection.

Semin Vet Med Surg (Small Anim). 1997 Aug;12(3):167-9. L The use of danazol in the therapy of immune-mediated disease of dogs.
Miller E.
Colorado State University, College of Veterinary Medicine and Biomedical Sciences, Department of Clinical Sciences, Fort Collins, USA.

Currently available therapeutic protocols for immune-mediated diseases in dogs and cats can be associated with poor response rates and a high incidence of side effects. The development of multidrug protocols often results in a synergistic effect that more efficiently suppresses the immune response. One drug that may be added to other therapies is danazol, an androgen with immunomodulating properties. Androgens are known to suppress aberrant immune responses, and the fact that immune-mediated diseases are more common in females supports this. Danazol has been used in humans with immune-mediated hemolytic anemia and thrombocytopenia with some success. Danazol appears to reduce the binding of immuno-globulin and complement to the red blood cell or platelet surface and also may alter cytokine concentrations. The use of danazol in dogs with immunemediated hemolytic anemia and thrombocytopenia has been reported; however, the small number of animals evaluated make it difficult to assess its usefulness in veterinary medicine.

J Am Anim Hosp Assoc. 1995 Jan-Feb;31(1):70-6. : Concurrent lymphangioma, immune-mediated thrombocytopenia, and von Willebrand's disease in a dog.
Woods JP, Johnstone IB, Bienzle D, Balson G, Gartley CJ.
Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Canada.

Lymphangioma, immune-mediated thrombocytopenia (IMT), and von Willebrand's disease (vWD) were diagnosed by histology, hematology, and a coagulation profile in a 14-month-old, female dachshund. Clinical and laboratory findings included ecchymotic inguinolabial swelling, thrombocytopenia, positive platelet factor-3 assay, prolonged buccal mucosal bleeding time, and subnormal von Willebrand factor antigen concentration and factor VIII activity. The IMT resolved with immunosuppressive glucocorticoid therapy. Histologic examination identified lymphangioma which was too extensive for surgical excision. The history and the clinical and laboratory findings were consistent with congenital vWD, although acquired vWD secondary to lymphangioma could not be ruled out.

: J Vet Intern Med. 1994 Sep-Oct;8(5):323-7. : Platelet dysfunction associated with immune-mediated thrombocytopenia in dogs.
Kristensen AT, Weiss DJ, Klausner JS.
Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul.

The effect of antiplatelet antibody on in vitro platelet function was investigated in 15 dogs with immune-mediated thrombocytopenia (ITP). Platelet aggregation was assessed after addition of serum from healthy dogs (n = 5) or dogs with ITP (n = 15) to platelet-rich plasma from a healthy donor dog. The aggregation responses to adenosine diphosphate, thrombin, and collagen/epinephrine were measured as the maximum aggregation observed after 2 minutes. In 13 of 15 dogs with ITP, maximal aggregation was significantly inhibited in response to ADP, thrombin, or collagen/epinephrine. The slope of the aggregation curve was decreased after addition of serum from 9 of 15 patients. A polyclonal rabbit anti-dog platelet antiserum induced inhibition of aggregation with all 3 agonists. Serum from control dogs neither inhibited nor activated platelet aggregation. Aggregation experiments were repeated with all 3 agonists after addition of patient immunoglobulin (Ig)G or IgG from a healthy dog to platelet-rich plasma. The IgG fraction from 9 of 10 dogs with ITP suppressed platelet aggregation. The IgG fraction from polyclonal rabbit anti-dog platelet antiserum inhibited platelet aggregation with all agonists. These results suggest that many canine ITP patients have circulating antibodies that, in addition to causing platelet destruction, may cause platelet dysfunction.

Cancer. 1992 Nov 1;70(9):2334-7.: Immune-mediated disease as a risk factor for canine lymphoma.
Keller ET.
Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison 53706.

BACKGROUND. Autoimmune diseases and neoplasia have been associated as occurring simultaneously in individuals. This study evaluated the association between the simultaneous occurrence of canine lymphoma and various immune-mediated diseases. METHODS. The Veterinary Medical Data Program, a national disease data registry for veterinary schools, was examined. The following immune-mediated disease categories were evaluated: lupus disorders, pemphigus disorders, autoimmune polyarthritis, immune-mediated hemolytic anemia, and immune-mediated thrombocytopenia. Odds ratios with 99% confidence intervals were calculated for the occurrence of lymphoma and each of the immune-mediated disorder categories. RESULTS. Only dogs with immune-mediated thrombocytopenia had a statistically significantly increased odds ratio (5.61; 99% confidence interval, 4.16-7.57) for the occurrence of lymphoma versus the general population. This association still was observed for immune-mediated thrombocytopenia when stratified by age, sex, and neutering status. CONCLUSION. Dogs with immune-mediated thrombocytopenia had a greater occurrence of lymphoma than dogs without immune-mediated thrombocytopenia.

J Vet Intern Med. 1990 Jan-Feb;4(1):4-7. : Therapy of immune mediated thrombocytopenia. A retrospective study of 15 dogs.
Jans HE, Armstrong PJ, Price GS.
Department of Companion Animal and Special Species Medicine, North Carolina State University, College of Veterinary Medicine, Raleigh 27606.

Fifteen dogs with immune mediated thrombocytopenia (IMT) were studied retrospectively. All dogs had a thrombocyte count below 50,000/microliters when response to therapy was studied. Platelet counts greater than 50,000/microliters were present in all dogs within 2-9 days of initiating medical therapy. Eight dogs experienced a single episode of thrombocytopenia and seven dogs relapsed over the following 5 to 24 months. Clinical parameters from dogs that experienced a single episode of IMT were compared with data from dogs that relapsed to determine whether any information would identify dogs that were prone to relapse. Signalment, severity of thrombocytopenia, and time to achieve a platelet count above 50,000/microliters were found not to differ (P greater than 0.05) between these two groups. Five of the seven dogs with relapsing IMT were splenectomized after 2 to 4 episodes (mean, 2.8 +/- 0.8) of thrombocytopenia over 2 to 14 months. The postoperative progress of these five dogs was followed for 6 to 17 months. Platelet counts were sustained above 200,000/microliters in 4/5 after splenectomy and it was possible to discontinue medical therapy in these dogs. In comparison, the 2 relapsing IMT cases that were not splenectomized continued to require intermittent immunosuppressive therapy. We conclude that signalment and routine pretreatment laboratory test results are not useful in distinguishing dogs with relapsing IMT from those that will experience one episode of IMT. Seemingly, splenectomy is useful in the management of dogs with relapsing IMT.

J Am Vet Med Assoc. 1989 Jan 1;194(1):76-8. : Use of danazol for treatment of corticosteroid-resistant immune-mediated thrombocytopenia in a dog.
Bloom JC, Meunier LD, Thiem PA, Sellers TS.
Department of Experimental Pathology, SmithKline & French Laboratories, King of Prussia, PA 19406.

A routine health screen of a 7 1/2-year-old female Beagle participating as a control in a long-term study revealed thrombocytopenia. Immune thrombocytopenia was diagnosed on the basis of regenerative bone marrow findings (high number of megakaryocytes) and evidence of antiplatelet antibodies. Treatment with prednisone at dosages up to 1 mg/kg of body weight every 12 hours resulted in limited improvement, with relapses of severe thrombocytopenia thwarting attempts to taper the corticosteroid, and was further complicated by side effects of the drug. Addition of danazol to the treatment regimen (5 mg/kg, q 12 h) resulted in remission of the thrombocytopenia within 2 weeks and permitted the dosage of prednisone to gradually be reduced and discontinued. Associated with this response was a decrease in platelet-associated IgG to values comparable with control samples.
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