Immune-mediated thrombocytopaenia

For similar conditions in man, see Immune thrombocytopenic purpura and Thrombotic thrombocytopenic purpura.
Immune-mediated thrombocytopaenia
Other namesImmune-mediated thrombocytopenia
SpecialtyHaematology
SymptomsLethargy, anorexia, pyrexia, haemorrhage, bruising
ComplicationsPlatelet destruction
Usual onsetBetween >1 and 14 years
CausesUnderlying condition (secondary IMT only)
Risk factorsBitches, certain breeds, neuter status
Diagnostic methodPlatelet count measurement (both) and exclusion of underlying conditions (primary)
TreatmentImmunosuppression, steroids, blood transfusion, therapeutic plasma exchange
MedicationCorticosteroids, azathioprine, prednisone
Prognosis74-97% short term survival rate

Immune-mediated thrombocytopaenia (IMT) is a disease common in dogs and rare in cats. The disease is characterised by a low platelet count caused by destruction of the platelets from the immune system. IMT is the most common cause of thrombocytopaenia in dogs.[1]

Signs and symptoms

Common symptoms of IMT include lethargy, anorexia, pyrexia, haemorrhage, and bruising.[1] Destruction of platelets occurs when immunoglobins attach to the surface of the platelet, which causes macrophages to initiate phagocytosis.[2] IMT is differentiated from other forms of thrombocytopaenia by the immune-mediated component of the condition.[3]

Causes

Primary immune-mediated thrombocytopaenia

The immune system mistakenly destroying normal thrombocytes is pathognomonic of primary IMT.[4]

Secondary immune-mediated thrombocytopaenia

Secondary IMT may be the result of viruses, parasites, or bacteria; neoplasia; drug-induced aetiology;[5] blood transfusion; allergic and vaccine reaction[6] which disrupts the homeostasis of the immune system and results in immune-mediated platelet destruction.[7][8][9]

Risk factors

Bitches are twice as likely as male dogs to be affected.[10] Breeds with documented predispositions are: cocker spaniels, miniature and toy poodles, Old English sheepdogs,[10] golden retrievers, and German shepherd dogs.[1] Neutered dogs have a significantly increased risk of developing IMT.[11]

Age of onset

Age of onset has been reported in the literature as ranging from >1–14 years. The median age is reported to be between 4 and 8.1 years.[6][10][12]

Diagnosis

Dogs usually present with lethargy, asthaenia, anorexia, or mild pyrexia. Signs of platelet dysfunction such as petechiae or ecchymosis, epistaxis or rhinorrhagia and in severe cases with haematuria; gingival or ocular haemorrhages are used to identify and diagnose thrombocytopaenia. Up to half of dogs may present with splenomegaly.[2][8][1]

Patients can be screened to check for drugs and toxins that may cause haemostasis or secondary IMT. PCR serology tests may be performed to screen for diseases.[13] Serum chemistry, coagulation panels, and Coombs tests can be performed to rule out or diagnose comorbidities including: von Willebrand's disease, haemophilia A, disseminated intravascular coagulation, immune-mediated haemolytic anaemia, or renal failure.[3][14]

Radiographic and ultrasonographic procedures can rule out splenic hemangiosarcoma, mast cell tumours, pancreatitis, infection, endocarditis, and other diseases with similar symptoms.[13][14] A biopsy of bone marrow can identify platelet production problems. Biopsies of diseased tissue can identify neoplasia through cytological evaluation.[8][13]

Differential diagnosis

Primary IMT is idiopathic and is diagnosed after exclusion of secondary IMT and other causes of thrombocytopaenia.[12][10] Measure of platelet counts are used to diagnose thrombocytopaenia ( >30,0000-50,000/μL).[15][16] Primary IMT makes up 5-15% of IMT cases.[17][18][19]

Treatment

Treatment varies based on whether or not it is primary or secondary IMT; however, all cases require immunosuppression.[1]

Immunosuppression

Immunosuppressive drugs are the most common treatment with corticosteroids being commonly used.[16] Vincristine and human intravenous immunogoblin have been shown to increase platelet count and improve recovery; however, none of these treatments have been shown to produce better long term survival than corticoseroid treatment.[18][20][5] Alternative immunosuppressants may be used in more severe cases such as: azathioprine, cyclophosphamide, leflunomide, danazol, mycophenolate, mofetil, and cyclosporine.[21][8] Azathioprine is not recommended for cats due to susceptibility to myelosuppressive effects.[22][23] In patients that do not respond well to immunosuppressive therapy or have constant relapse a splenectomy may be undertaken. Removal of the spleen removes the primary site of clearance of platelets and prevents production of autoantibodies.[1] Survival following splenectomy is unpredictable and lifelong care is often needed.[1][8]

Blood transfusion

Blood transfusions are typically used in patients with secondary anaemia rather than isolated thrombocytopaenia as the platelets will likely be destroyed on transfusion.[8] Fluid therapy may be used to correct hypovolaemia and dehydration in cases without anaemia; however, this decreases platelet production.[15][8]

Therapeutic plasma exchange

Therapeutic plasma exchange (TPE) is a novel treatment for immune-mediated diseases and little research has been done for the effectiveness of TPE and patients with IMT.[15] TPE requires removing the patient's plasma which contains antibodies and replacing it with fluids such as sodium chloride, frozen plasma, packed red blood cells, and hetastarch.[15] Kopecny et al. found this treatment to be effective in three out of four dogs with IMT who were unresponsive to other treatments.[15] Francey et al. found that dogs treated with TPE for IMT had similar prognosis to those treated differently; however, Francey et al. discussed its safety as a treatment and recommended further research.[24][a]

Steroids

Prednisone and prednisolone are steroids used to suppress immune response to restore platelet levels.[5][8][1] Side effects of these include adrenal atrophy, proteinuria and glomerular changes, weight loss, dermatitis, regurgitation, diarrhoea, gastroinestinal ulceration, hyperglycaemia, polyuria, polydipsia, decreased T4 levels, and other side effects.[21][25] Patients generally start on a higher rate which is tapered off.[3][25] Tapering is commenced once patients have gone two weeks with a normal platelet count.[8][25]

Prognosis

Studies have identified short-term survival rates of 74–97% with a recurrence rate of 24–58%. Melaena and high blood urea nitrogen were associated with worse outcomes. Cummings and Rizzo identified a 60% survival rate in cases comorbid with melaena and high blood urea nitrogen.[5][26][10][27][28] A study following up on 45 dogs identified with IMT after 1 year found a mortality rate of 11.9%. 89.6% of dogs survived to discharge and 31% of those discharged relapsed, with an average of 78 days for dogs with multiple relapses and 149 days for dogs with only one relapse. The longest time between discharge and relapse was over 3 years. Seven dogs experienced relapse more than once and one dog relapsed five times before being euthanised.[16] In dogs with a platelet count below < 30,000 cells/μL there is an increased risk of spontaneous haemorrhage;[26] however, haemorrhage cannot be predicted in dogs with IMT.[29]

Notes

  1. ^ This study used a different fluid to Kopecny et al.

References

  1. ^ a b c d e f g h Holt, Susan; Riley, Isabell (2019-06-02). "Canine immune-mediated thrombocytopenia". The Veterinary Nurse. 10 (5): 264–269. doi:10.12968/vetn.2019.10.5.264. ISSN 2044-0065. S2CID 196511905.
  2. ^ a b Harvey, John W. (2011-12-20). Veterinary Hematology. St. Louis, Mo: Elsevier Health Sciences. pp. 182–183. ISBN 978-1-4377-0173-9.
  3. ^ a b c Chartier, Marie. "Canine Primary IMT: Profile". Clinician's Brief. Retrieved 22 February 2024.
  4. ^ Lewis, Courtney (June 2023). "Immune-mediated thrombocytopaenia". New Zealand Veterinary Nurse Journal. 29 (106): 10–18.
  5. ^ a b c d Cummings, F. O.; Rizzo, S. A. (2017). "Treatment of presumptive primary immune-mediated thrombocytopenia with mycophenolate mofetil versus cyclosporine in dogs". Journal of Small Animal Practice. 58 (2): 96–102. doi:10.1111/jsap.12621. ISSN 0022-4510. PMID 28160307.
  6. ^ a b Day, Michael J.; Kohn, Barbara (2012-05-29). BSAVA Manual of Canine and Feline Haematology and Transfusion Medicine. Gloucester: BSAVA. ISBN 978-1-905319-29-9.
  7. ^ Ellis, J.; Bell, R.; Barnes, D.C.; Miller, R. (2018). "Prevalence and disease associations in feline thrombocytopenia: a retrospective study of 194 cases". Journal of Small Animal Practice. 59 (9): 531–538. doi:10.1111/jsap.12814. ISSN 0022-4510. PMID 29355998. S2CID 1198103.
  8. ^ a b c d e f g h i Whitley, Nat (2020). "Dealing with immune-mediated haematological diseases in dogs and cats 2. Thrombocytopenia and Evan's syndrome". In Practice. 42 (1): 20–25. doi:10.1136/inp.l6458. ISSN 0263-841X. S2CID 213836183.
  9. ^ Shropshire, Sarah; Dow, Steven; Lappin, Michael (2020). "Detection and dynamics of anti-platelet antibodies in thrombocytopenic dogs with and without idiopathic immune thrombocytopenia". Journal of Veterinary Internal Medicine. 34 (2): 700–709. doi:10.1111/jvim.15737. ISSN 0891-6640. PMC 7096660. PMID 32072705.
  10. ^ a b c d e O'Marra, Shana K.; Delaforcade, Armelle M.; Shaw, Scott P. (2011-02-01). "Treatment and predictors of outcome in dogs with immune-mediated thrombocytopenia". Journal of the American Veterinary Medical Association. 238 (3). American Veterinary Medical Association (AVMA): 346–352. doi:10.2460/javma.238.3.346. ISSN 0003-1488. PMID 21281218.
  11. ^ Sundburg, Crystal R.; Belanger, Janelle M.; Bannasch, Danika L.; Famula, Thomas R.; Oberbauer, Anita M. (2016). "Gonadectomy effects on the risk of immune disorders in the dog: a retrospective study". BMC Veterinary Research. 12 (1): 278. doi:10.1186/s12917-016-0911-5. ISSN 1746-6148. PMC 5146839. PMID 27931211.
  12. ^ a b Lewis, David C.; Meyers, Kenneth M. (1996). "Canine Idiopathic Thrombocytopenic Purpura". Journal of Veterinary Internal Medicine. 10 (4): 207–218. doi:10.1111/j.1939-1676.1996.tb02052.x. ISSN 0891-6640. PMID 8819045.
  13. ^ a b c LeVine, Dana N.; Brooks, Marjory B. (2019). "Immune thrombocytopenia (ITP): Pathophysiology update and diagnostic dilemmas". Veterinary Clinical Pathology. 48 (S1): 17–28. doi:10.1111/vcp.12774. ISSN 0275-6382. PMID 31538353. S2CID 202703012.
  14. ^ a b Allen, Julie. "Differential Diagnosis: Thrombocytopenia in Dogs & Cats". Clinician's Brief. Retrieved 22 February 2024.
  15. ^ a b c d e Kopecny, Lucy; Palm, Carrie A.; Naylor, Sean; Kirby, John; Cowgill, Larry D. (2020). "Application of therapeutic plasma exchange in dogs with immune-mediated thrombocytopenia". Journal of Veterinary Internal Medicine. 34 (4): 1576–1581. doi:10.1111/jvim.15836. ISSN 0891-6640. PMC 7379011. PMID 32557826.
  16. ^ a b c Simpson, K.; Chapman, P.; Klag, A. (2018). "Long-term outcome of primary immune-mediated thrombocytopenia in dogs". Journal of Small Animal Practice. 59 (11): 674–680. doi:10.1111/jsap.12912. ISSN 0022-4510. PMID 30102418. S2CID 51967860.
  17. ^ Ahn, Yeon S.; Byrnes, John J.; Harrington, William J.; Cayer, Marilyn L.; Smith, David S.; Brunskill, Dennis E.; Pall, Lorraine M. (1978-05-18). "The Treatment of Idiopathic Thrombocytopenia with Vinblastine-Loaded Platelets". New England Journal of Medicine. 298 (20): 1101–1107. doi:10.1056/NEJM197805182982001. ISSN 0028-4793. PMID 565464.
  18. ^ a b Balog, K.; Huang, A.A.; Sum, S.O; Moore, G.E.; Thompson, C.; Scott-Moncrieff, J.C. (2013-03-25). "A Prospective Randomized Clinical Trial of Vincristine versus Human Intravenous Immunoglobulin for Acute Adjunctive Management of Presumptive Primary Immune-Mediated Thrombocytopenia in Dogs". Journal of Veterinary Internal Medicine. 27 (3). Wiley: 536–541. doi:10.1111/jvim.12066. ISSN 0891-6640. PMID 23527952.
  19. ^ SC, Helfand; NC, Jain; M, Paul (1984). "Vincristine-loaded platelet therapy for idiopathic thrombocytopenia in a dog". Journal of the American Veterinary Medical Association. 185 (2). J Am Vet Med Assoc: 224–226. ISSN 0003-1488. PMID 6746398. Retrieved 2024-02-22.
  20. ^ Bianco, D.; Armstrong, P.J.; Washabau, R.J. (2009). "A Prospective, Randomized, Double-Blinded, Placebo-Controlled Study of Human Intravenous Immunoglobulin for the Acute Management of Presumptive Primary Immune-Mediated Thrombocytopenia in Dogs". Journal of Veterinary Internal Medicine. 23 (5). Wiley: 1071–1078. doi:10.1111/j.1939-1676.2009.0358.x. ISSN 0891-6640. PMID 19674280.
  21. ^ a b Brooks, Wendy (8 August 2017). "Immune-Mediated Thrombocytopenia (IMT)". Vin.com. VIN. Retrieved 23 February 2024.
  22. ^ McCullough S. Immune-mediated hemolytic anemia: Understanding the nemesis. Vet Clin North Am Small Anim Pract 2003; 33:1295-1315.
  23. ^ Plumb D. Plumb's Veterinary Drug Handbook, 7th ed. Ames, IA: PharmaVet Inc 2011
  24. ^ Francey, Thierry; Etter, Mathieu; Schweighauser, Ariane (2021). "Evaluation of membrane-based therapeutic plasma exchange as adjunctive treatment for immune-mediated hematologic disorders in dogs". Journal of Veterinary Internal Medicine. 35 (2): 925–935. doi:10.1111/jvim.16049. ISSN 0891-6640. PMC 7995402. PMID 33571376.
  25. ^ a b c British Small Animal Veterinary Association. (2017). BSAVA small animal formulary (9th ed., pp. 325).
  26. ^ a b DA, Williams; L, Maggio-Price (1984). "Canine idiopathic thrombocytopenia: clinical observations and long-term follow-up in 54 cases". Journal of the American Veterinary Medical Association. 185 (6). J Am Vet Med Assoc: 660–663. ISSN 0003-1488. PMID 6541641. Retrieved 2024-02-22.
  27. ^ Putsche, Jutta C.; Kohn, Barbara (2008-09-01). "Primary Immune-mediated Thrombocytopenia in 30 Dogs (1997–2003)". Journal of the American Animal Hospital Association. 44 (5). American Animal Hospital Association: 250–257. doi:10.5326/0440250. ISSN 0587-2871. PMID 18762561.
  28. ^ Jans, Heather E.; Armstrong, P. Jane; Price, G. Sylvester (1990). "Therapy of Immune Mediated Thrombocytopenia". Journal of Veterinary Internal Medicine. 4 (1). Wiley: 4–7. doi:10.1111/j.1939-1676.1990.tb00867.x. ISSN 0891-6640. PMID 2308120.
  29. ^ Abrams-Ogg, Anthony C.G (2003). "Triggers for prophylactic use of platelet transfusions and optimal platelet dosing in thrombocytopenic dogs and cats". Veterinary Clinics of North America: Small Animal Practice. 33 (6). Elsevier BV: 1401–1418. doi:10.1016/s0195-5616(03)00095-0. ISSN 0195-5616. PMID 14664205.

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