Title: Immune-mediated thrombocytopaenia

{{Short description|Immune related haematological animal disease}}
{{for|similar conditions in man|Immune thrombocytopenic purpura|Thrombotic thrombocytopenic purpura}}
{{Infobox medical condition
 |name            = Immune-mediated thrombocytopaenia
 |synonym       = Immune-mediated thrombocytopenia
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 |specialty       = [[Haematology]]
 |symptoms        = [[Lethargy]], [[anorexia]], [[pyrexia]], [[haemorrhage]], [[bruising]]
 |complications   = Platelet destruction
 |onset           = Between &gt;1 and 14 years
 |duration        = 
 |types           = 
 |causes          = Underlying condition (secondary IMT only)
 |risks           = Bitches, certain breeds, neuter status
 |diagnosis       = Platelet count measurement (both) and exclusion of underlying conditions (primary)
 |differential    = 
 |prevention      = 
 |treatment       = Immunosuppression, steroids, blood transfusion, therapeutic plasma exchange
 |medication      = Corticosteroids, azathioprine, prednisone
 |prognosis       = 74-97% short term survival rate
 |frequency       = &lt;!-- also |incidence= or |prevalence= --&gt;
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'''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.&lt;ref name=&quot;Holt2019&quot;&gt;{{cite journal | last1=Holt | first1=Susan | last2=Riley | first2=Isabell | title=Canine immune-mediated thrombocytopenia | journal=The Veterinary Nurse | volume=10 | issue=5 | date=2019-06-02 | issn=2044-0065 | doi=10.12968/vetn.2019.10.5.264 | pages=264–269| s2cid=196511905 }}&lt;/ref&gt;

==Signs and symptoms==
Common symptoms of IMT include [[lethargy]], [[anorexia]], [[pyrexia]], [[haemorrhage]], and bruising.&lt;ref name=&quot;Holt2019&quot;/&gt; Destruction of platelets occurs when [[immunoglobin]]s attach to the surface of the platelet, which causes [[macrophage]]s to initiate [[phagocytosis]].&lt;ref name=&quot;Harvey2011&quot;&gt;{{cite book | last=Harvey | first=John W. | title=Veterinary Hematology | publisher=Elsevier Health Sciences | publication-place=St. Louis, Mo | date=2011-12-20 | isbn=978-1-4377-0173-9 | pages=182–183}}&lt;/ref&gt; IMT is differentiated from other forms of thrombocytopaenia by the immune-mediated component of the condition.&lt;ref name=&quot;Chartier2015&quot;&gt;{{cite web |last1=Chartier |first1=Marie |title=Canine Primary IMT: Profile |url=https://www.cliniciansbrief.com/article/canine-primary-idiopathic-immune-mediated-thrombocytopenia |website=Clinician's Brief |access-date=22 February 2024}}&lt;/ref&gt;

==Causes==
===Primary immune-mediated thrombocytopaenia===
The immune system mistakenly destroying normal thrombocytes is pathognomonic of primary IMT.&lt;ref name=&quot;Lewis2023&quot;&gt;{{cite journal |last1=Lewis |first1=Courtney |title=Immune-mediated thrombocytopaenia |journal=New Zealand Veterinary Nurse Journal |date=June 2023 |volume=29 |issue=106 |pages=10–18}}&lt;/ref&gt;

===Secondary immune-mediated thrombocytopaenia===
Secondary IMT may be the result of [[viruses]], [[parasite]]s, or [[bacteria]]; [[neoplasia]]; drug-induced aetiology;&lt;ref name=&quot;Cummings2017&quot;&gt;{{cite journal | last1=Cummings | first1=F. O. | last2=Rizzo | first2=S. A. | title=Treatment of presumptive primary immune-mediated thrombocytopenia with mycophenolate mofetil versus cyclosporine in dogs | journal=Journal of Small Animal Practice | volume=58 | issue=2 | date=2017 | issn=0022-4510 | doi=10.1111/jsap.12621 | pages=96–102| pmid=28160307 }}&lt;/ref&gt; blood transfusion; allergic and vaccine reaction&lt;ref name=&quot;Day2012&quot;&gt;{{cite book | last1=Day | first1=Michael J. | last2=Kohn | first2=Barbara | title=BSAVA Manual of Canine and Feline Haematology and Transfusion Medicine | publisher=BSAVA | publication-place=Gloucester | date=2012-05-29 | isbn=978-1-905319-29-9 | page=}}&lt;/ref&gt; which disrupts the [[homoeostasis]] of the immune system and results in immune-mediated platelet destruction.&lt;ref name=&quot;Ellis2018&quot;&gt;{{cite journal | last1=Ellis | first1=J. | last2=Bell | first2=R. | last3=Barnes | first3=D.C. | last4=Miller | first4=R. | title=Prevalence and disease associations in feline thrombocytopenia: a retrospective study of 194 cases | journal=Journal of Small Animal Practice | volume=59 | issue=9 | date=2018 | issn=0022-4510 | doi=10.1111/jsap.12814 | pages=531–538| pmid=29355998 | s2cid=1198103 }}&lt;/ref&gt;&lt;ref name=&quot;Whitley2020&quot;&gt;{{cite journal | last=Whitley | first=Nat | title=Dealing with immune-mediated haematological diseases in dogs and cats 2. Thrombocytopenia and Evan's syndrome | journal=In Practice | volume=42 | issue=1 | date=2020 | issn=0263-841X | doi=10.1136/inp.l6458 | pages=20–25| s2cid=213836183 }}&lt;/ref&gt;&lt;ref name=&quot;Shropshire2020&quot;&gt;{{cite journal | last1=Shropshire | first1=Sarah | last2=Dow | first2=Steven | last3=Lappin | first3=Michael | title=Detection and dynamics of anti-platelet antibodies in thrombocytopenic dogs with and without idiopathic immune thrombocytopenia | journal=Journal of Veterinary Internal Medicine | volume=34 | issue=2 | date=2020 | issn=0891-6640 | pmid=32072705 | pmc=7096660 | doi=10.1111/jvim.15737 | pages=700–709}}&lt;/ref&gt;

===Risk factors===
Bitches are twice as likely as male dogs to be affected.&lt;ref name=&quot;OMarra2011&quot;&gt;{{cite journal | last1=O'Marra | first1=Shana K. | last2=Delaforcade | first2=Armelle M. | last3=Shaw | first3=Scott P. | title=Treatment and predictors of outcome in dogs with immune-mediated thrombocytopenia | journal=Journal of the American Veterinary Medical Association | publisher=American Veterinary Medical Association (AVMA) | volume=238 | issue=3 | date=2011-02-01 | issn=0003-1488 | doi=10.2460/javma.238.3.346 | pages=346–352| pmid=21281218 }}&lt;/ref&gt; Breeds with documented predispositions are: [[cocker spaniel]]s, miniature and toy [[Poodle]]s, [[Old English Sheepdog]]s,&lt;ref name=&quot;OMarra2011&quot;/&gt; [[Golden Retriever]]s, and [[German Shepherd Dog]]s.&lt;ref name=&quot;Holt2019&quot;/&gt; Neutered dogs have a significantly increased risk of developing IMT.&lt;ref name=&quot;Sundburg2016&quot;&gt;{{cite journal | last1=Sundburg | first1=Crystal R. | last2=Belanger | first2=Janelle M. | last3=Bannasch | first3=Danika L. | last4=Famula | first4=Thomas R. | last5=Oberbauer | first5=Anita M. | title=Gonadectomy effects on the risk of immune disorders in the dog: a retrospective study | journal=BMC Veterinary Research | volume=12 | issue=1 | date=2016 | issn=1746-6148 | pmid=27931211 | pmc=5146839 | doi=10.1186/s12917-016-0911-5 | doi-access=free | page=278}}&lt;/ref&gt;

===Age of onset===
Age of onset has been reported in the literature as ranging from &gt;1–14 years. The median age is reported to be between 4 and 8.1 years.&lt;ref name=&quot;Day2012&quot;/&gt;&lt;ref name=&quot;OMarra2011&quot;/&gt;&lt;ref name=&quot;Lewis1996&quot;&gt;{{cite journal | last1=Lewis | first1=David C. | last2=Meyers | first2=Kenneth M. | title=Canine Idiopathic Thrombocytopenic Purpura | journal=Journal of Veterinary Internal Medicine | volume=10 | issue=4 | date=1996 | issn=0891-6640 | doi=10.1111/j.1939-1676.1996.tb02052.x | pages=207–218| pmid=8819045 | doi-access=free }}&lt;/ref&gt;

==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]].&lt;ref name=&quot;Harvey2011&quot;/&gt;&lt;ref name=&quot;Whitley2020&quot;/&gt;&lt;ref name=&quot;Holt2019&quot;/&gt;

Patients can be screened to check for drugs and toxins that may cause [[haemostasis]] or secondary IMT. [[PCR test|PCR]] serology tests may be performed to screen for diseases.&lt;ref name=&quot;LeVine2019&quot;&gt;{{cite journal | last1=LeVine | first1=Dana N. | last2=Brooks | first2=Marjory B. | title=Immune thrombocytopenia (ITP): Pathophysiology update and diagnostic dilemmas | journal=Veterinary Clinical Pathology | volume=48 | issue=S1 | date=2019 | issn=0275-6382 | doi=10.1111/vcp.12774 | pages=17–28| pmid=31538353 | s2cid=202703012 }}&lt;/ref&gt; [[Serum chemistry]], [[coagulation panel]]s, and [[Coombs test]]s 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]].&lt;ref name=&quot;Chartier2015&quot;/&gt;&lt;ref name=&quot;Allen2020&quot;&gt;{{cite web |last1=Allen |first1=Julie |title=Differential Diagnosis: Thrombocytopenia in Dogs &amp; Cats |url=https://www.cliniciansbrief.com/article/differential-diagnosis-thrombocytopenia |website=Clinician's Brief |access-date=22 February 2024}}&lt;/ref&gt;

[[Radiographic]] and [[ultrasonographic]] procedures can rule out [[Hemangiosarcoma|splenic hemangiosarcoma]], [[mast cell tumour]]s, [[pancreatitis]], infection, [[endocarditis]], and other diseases with similar symptoms.&lt;ref name=&quot;LeVine2019&quot;/&gt;&lt;ref name=&quot;Allen2020&quot;/&gt; A [[biopsy]] of [[bone marrow]] can identify platelet production problems. Biopsies of diseased tissue can identify neoplasia through cytological evaluation.&lt;ref name=&quot;Whitley2020&quot;/&gt;&lt;ref name=&quot;LeVine2019&quot;/&gt;

===Differential diagnosis===
Primary IMT is [[idiopathic]] and is diagnosed after exclusion of secondary IMT and other causes of thrombocytopaenia.&lt;ref name=&quot;Lewis1996&quot;/&gt;&lt;ref name=&quot;OMarra2011&quot;/&gt; Measure of platelet counts are used to diagnose thrombocytopaenia ( &gt;30,0000-50,000/μL).&lt;ref name=&quot;Kopecny2020&quot;&gt;{{cite journal | last1=Kopecny | first1=Lucy | last2=Palm | first2=Carrie A. | last3=Naylor | first3=Sean | last4=Kirby | first4=John | last5=Cowgill | first5=Larry D. | title=Application of therapeutic plasma exchange in dogs with immune-mediated thrombocytopenia | journal=Journal of Veterinary Internal Medicine | volume=34 | issue=4 | date=2020 | issn=0891-6640 | pmid=32557826 | pmc=7379011 | doi=10.1111/jvim.15836 | pages=1576–1581}}&lt;/ref&gt;&lt;ref name=&quot;Simpson2018&quot;&gt;{{cite journal | last1=Simpson | first1=K. | last2=Chapman | first2=P. | last3=Klag | first3=A. | title=Long-term outcome of primary immune-mediated thrombocytopenia in dogs | journal=Journal of Small Animal Practice | volume=59 | issue=11 | date=2018 | issn=0022-4510 | doi=10.1111/jsap.12912 | pages=674–680| pmid=30102418 | s2cid=51967860 }}&lt;/ref&gt; Primary IMT makes up 5-15% of IMT cases.&lt;ref&gt;{{cite journal | last1=Ahn | first1=Yeon S. | last2=Byrnes | first2=John J. | last3=Harrington | first3=William J. | last4=Cayer | first4=Marilyn L. | last5=Smith | first5=David S. | last6=Brunskill | first6=Dennis E. | last7=Pall | first7=Lorraine M. | title=The Treatment of Idiopathic Thrombocytopenia with Vinblastine-Loaded Platelets | journal=New England Journal of Medicine | volume=298 | issue=20 | date=1978-05-18 | issn=0028-4793 | doi=10.1056/NEJM197805182982001 | pages=1101–1107| pmid=565464 }}&lt;/ref&gt;&lt;ref name=&quot;Balog2013&quot;&gt;{{cite journal | last1=Balog | first1=K. | last2=Huang | first2=A.A. | last3=Sum | first3=S.O | last4=Moore | first4=G.E. | last5=Thompson | first5=C. | last6=Scott-Moncrieff | first6=J.C. | title=A Prospective Randomized Clinical Trial of Vincristine versus Human Intravenous Immunoglobulin for Acute Adjunctive Management of Presumptive Primary Immune-Mediated Thrombocytopenia in Dogs | journal=Journal of Veterinary Internal Medicine | publisher=Wiley | volume=27 | issue=3 | date=2013-03-25 | issn=0891-6640 | doi=10.1111/jvim.12066 | pages=536–541| pmid=23527952 | doi-access=free }}&lt;/ref&gt;&lt;ref&gt;{{cite journal | last1=SC | first1=Helfand | last2=NC | first2=Jain | last3=M | first3=Paul | title=Vincristine-loaded platelet therapy for idiopathic thrombocytopenia in a dog | journal=Journal of the American Veterinary Medical Association | date=1984 | publisher=J Am Vet Med Assoc | volume=185 | issue=2 | pages=224–226 | issn=0003-1488 | pmid=6746398 }}&lt;/ref&gt;

==Treatment==
Treatment varies based on whether or not it is primary or secondary IMT; however, all cases require immunosuppression.&lt;ref name=&quot;Holt2019&quot;/&gt;

===Immunosuppression===
Immunosuppressive drugs are the most common treatment with [[corticosteroid]]s being commonly used.&lt;ref name=&quot;Simpson2018&quot;/&gt; [[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.&lt;ref name=&quot;Balog2013&quot;/&gt;&lt;ref name=&quot;Bianco2009&quot;&gt;{{cite journal | last1=Bianco | first1=D. | last2=Armstrong | first2=P.J. | last3=Washabau | first3=R.J. | title=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=Journal of Veterinary Internal Medicine | publisher=Wiley | volume=23 | issue=5 | year=2009 | issn=0891-6640 | doi=10.1111/j.1939-1676.2009.0358.x | pages=1071–1078| pmid=19674280 | doi-access=free }}&lt;/ref&gt;&lt;ref name=&quot;Cummings2017&quot;/&gt;
Alternative immunosuppressants may be used in more severe cases such as: [[azathioprine]], [[cyclophosphamide]], [[leflunomide]], [[danazol]], [[mycophenolate]], [[mofetil]], and [[cyclosporine]].&lt;ref name=&quot;Brooks2019&quot;&gt;{{cite journal |last1=Brooks |first1=Wendy |title=Immune-Mediated Thrombocytopenia (IMT) |url=https://veterinarypartner.vin.com/default.aspx?pid=19239&amp;id=4951884 |website=Vin.com |date=8 August 2017 |publisher=VIN |access-date=23 February 2024}}&lt;/ref&gt;&lt;ref name=&quot;Whitley2020&quot;/&gt; Azathioprine is not recommended for cats due to susceptibility to myelosuppressive effects.&lt;ref&gt;McCullough S. Immune-mediated hemolytic anemia: Understanding the nemesis. Vet Clin North Am Small Anim Pract 2003; 33:1295-1315.&lt;/ref&gt;&lt;ref&gt;Plumb D. Plumb's Veterinary Drug Handbook, 7th ed. Ames, IA: PharmaVet Inc 2011&lt;/ref&gt;
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.&lt;ref name=&quot;Holt2019&quot;/&gt; Survival following splenectomy is unpredictable and lifelong care is often needed.&lt;ref name=&quot;Holt2019&quot;/&gt;&lt;ref name=&quot;Whitley2020&quot;/&gt;

===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.&lt;ref name=&quot;Whitley2020&quot;/&gt; Fluid therapy may be used to correct [[hypovolaemia]] and [[dehydration]] in cases without anaemia; however, this decreases platelet production.&lt;ref name=&quot;Kopecny2020&quot;/&gt;&lt;ref name=&quot;Whitley2020&quot;/&gt;

===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.&lt;ref name=&quot;Kopecny2020&quot;/&gt; 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]].&lt;ref name=&quot;Kopecny2020&quot;/&gt; Kopecny et al. found this treatment to be effective in three out of four dogs with IMT who were unresponsive to other treatments.&lt;ref name=&quot;Kopecny2020&quot;/&gt; 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.&lt;ref name=&quot;Francey2021&quot;&gt;{{cite journal | last1=Francey | first1=Thierry | last2=Etter | first2=Mathieu | last3=Schweighauser | first3=Ariane | title=Evaluation of membrane-based therapeutic plasma exchange as adjunctive treatment for immune-mediated hematologic disorders in dogs | journal=Journal of Veterinary Internal Medicine | volume=35 | issue=2 | date=2021 | issn=0891-6640 | pmid=33571376 | pmc=7995402 | doi=10.1111/jvim.16049 | pages=925–935}}&lt;/ref&gt;{{efn |This study used a different fluid to Kopecny et al.}}

===Steroids===
[[Prednisone]] and [[prednisolone]] are steroids used to suppress immune response to restore platelet levels.&lt;ref name=&quot;Cummings2017&quot;/&gt;&lt;ref name=&quot;Whitley2020&quot;/&gt;&lt;ref name=&quot;Holt2019&quot;/&gt; Side effects of these include [[adrenal atrophy]], [[proteinuria]] and [[glomerular]] changes, weight loss, [[dermatitis]], [[Regurgitation (digestion)|regurgitation]], [[diarrhoea]], [[gastroinestinal ulceration]], [[hyperglycaemia]], [[polyuria]], [[polydipsia]], decreased T4 levels, and other side effects.&lt;ref name=&quot;Brooks2019&quot;/&gt;&lt;ref name=&quot;BSAVA2017&quot;&gt;British Small Animal Veterinary Association. (2017). BSAVA
small animal formulary (9th ed., pp. 325).&lt;/ref&gt; Patients generally start on a higher rate which is tapered off.&lt;ref name=&quot;Chartier2015&quot;/&gt;&lt;ref name=&quot;BSAVA2017&quot;/&gt; Tapering is commenced once patients have gone two weeks with a normal platelet count.&lt;ref name=&quot;Whitley2020&quot;/&gt;&lt;ref name=&quot;BSAVA2017&quot;/&gt;

==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.&lt;ref name=&quot;Cummings2017&quot;/&gt;&lt;ref name=&quot;Williams1996&quot;&gt;{{cite journal | last1=DA | first1=Williams | last2=L | first2=Maggio-Price | title=Canine idiopathic thrombocytopenia: clinical observations and long-term follow-up in 54 cases | journal=Journal of the American Veterinary Medical Association | date=1984 | publisher=J Am Vet Med Assoc | volume=185 | issue=6 | pages=660–663 | issn=0003-1488 | pmid=6541641 }}&lt;/ref&gt;&lt;ref name=&quot;OMarra2011&quot;/&gt;&lt;ref name=&quot;Kohn2008&quot;&gt;{{cite journal | last1=Putsche | first1=Jutta C. | last2=Kohn | first2=Barbara | title=Primary Immune-mediated Thrombocytopenia in 30 Dogs (1997–2003) | journal=Journal of the American Animal Hospital Association | publisher=American Animal Hospital Association | volume=44 | issue=5 | date=2008-09-01 | issn=0587-2871 | doi=10.5326/0440250 | pages=250–257| pmid=18762561 }}&lt;/ref&gt;&lt;ref name=&quot;Jans1990&quot;&gt;{{cite journal | last1=Jans | first1=Heather E. | last2=Armstrong | first2=P. Jane | last3=Price | first3=G. Sylvester | title=Therapy of Immune Mediated Thrombocytopenia | journal=Journal of Veterinary Internal Medicine | publisher=Wiley | volume=4 | issue=1 | year=1990 | issn=0891-6640 | doi=10.1111/j.1939-1676.1990.tb00867.x | pages=4–7| pmid=2308120 | doi-access=free }}&lt;/ref&gt; 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.&lt;ref name=&quot;Simpson2018&quot;/&gt; In dogs with a platelet count below &lt; 30,000 cells/μL there is an increased risk of spontaneous [[haemorrhage]];&lt;ref name=&quot;Williams1996&quot;/&gt; however, haemorrhage cannot be predicted in dogs with IMT.&lt;ref name=&quot;Abrams2003&quot;&gt;{{cite journal | last=Abrams-Ogg | first=Anthony C.G | title=Triggers for prophylactic use of platelet transfusions and optimal platelet dosing in thrombocytopenic dogs and cats | journal=Veterinary Clinics of North America: Small Animal Practice | publisher=Elsevier BV | volume=33 | issue=6 | year=2003 | issn=0195-5616 | doi=10.1016/s0195-5616(03)00095-0 | pages=1401–1418| pmid=14664205 }}&lt;/ref&gt;

==Notes==
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==References==
{{reflist}}

[[Category:Dog diseases]]