4.3.3: Immune-mediated disease 2 Flashcards
How can IMHA cause death?
- Multi-organ failure to hypoxia
- Thromboembolism in lungs or brain (blood cells quite sticky) -> put on clot prevention
Treatment of IMHA
- Identifying the underlying trigger and treat where possible e.g. Doxycycline for Mycoplasma haemofelis
- If no underlying cause -> immunosuppresion: glucocorticoids, azathioprine, mycophenolate mofetil, cyclosporin, leflunomide
- Transfusion if animal severely anaemic
Use of glucocorticoids for IMHA treatment
- In many patients, glucocorticoids alone will achieve remission
- Dogs: oral prednisolone 2mg/kg q24hr
- Cats: oral prednisolone 2mg/kg q24hr
- Start dose needs to be high so immunosuppressive, then taper to avoid side effects
Side effects of glucocorticoids
- PUPD
- Polyphagia
- Hepatomegaly
- Pot belly
- Muscle atrophy
- Alopecia
- Increased susceptibility to infection
- (Basically iatrogenic Cushing’s)
How long will you need to continue immunosuppressive therapy for to treat IMHA?
- Regardless of drug used, uncommon for patients to respond in less than 5-10 days
- Taper glucocorticoids over weeks to avoid side effects
Most patients need months of treatment
True/false: when treating IMHA, it is most effective to use a combination of immunosuppressive drugs from the start.
False
* Use one drug at a time to start with, and add in others later if having issues.
* Using one drug at a time (with enough time) will allow you to see side effects
* Using multiple drugs together will predispose to serious infections
Use of azathioprine to treat IMHA
- =purine synthesis inhibitor that inhibits lymphocyte proliferation
- Well tolerated in dogs; some experience reversible hepatomegaly
- Dangerously myelosuppressive and thus not recommended in cats
Side effects of mycophenolate mofetil
20% of dogs treated get diarrhoea
Cyclosporin for treatment of IMHA
- =Calcineurin inhibitor that inhibits T cell function
- Most common side effects: nausea and vomiting
- Has no marrow suppressive effects so is the preferred agent for dogs with poorly regenerative IMHA
How do you prevent thromboembolism in a patient with IMHA?
Thromboprophylactic therapy such as:
* Unfractionated heparin
* Enoxaparin
* Rivaroxaban
* Clopidogrel (this is an oral anti-platelet drug)
* Low dose aspirin
Mortality rate in dogs with IMHA
- High >50%
- Most deaths occur a few months after presentation due to severe anaemia/ pulmonary thromboembolism/ euthanasia due to client intolerance of high cost therapy ± side effects
- If they survive the first few months, long-term prognosis is fair; 20% relapse
- Most dogs - treatment can be discontinued within 6-12 of presentation; some require lifelong immunosuppressives
- Most cats respond well to standard therapy
True/false: animals with IMTP often have subclinical disease.
True
Many will only present clinically when they have concurrent anaemia and classical signs associated with this e.g. tachycardia, tachypnoea, pale mm, bounding pulses
Possible causes of secondary IMTP
- Drugs
- Infection
- Polyimmune syndrome
- Platelet transfusion (done in USA)
- Vaccination
To diagnose an immune-mediated thrombocytopaenia (IMTP) you must first rule out…
primary causes of platelet reduction (i.e. consumption or lack of production)
Clinical signs of IMTP
If seen, these are attributable to failure of primary haemostasis
* Petechiae on gums
* Ecchymoses
* Haematomas
* Epistaxis
* Melena/ haematochezia from GIT bleeding
* Haematuria from bleeding into urinary tract (differentiate from haemoglobinuria by cytology)
* Retinal haemorrhage, hyphaemia, anterior uveitis
* (Intracavitary bledding is very rare)
Lab findings with IMTP
- Low platelet count (check for clumping)
- In primary IMTP, biochem and coagulation tests often normal
- Haematology - check for concurrent anaemia/ cell line reduction that could indicate bone marrow disease
- Imaging - rule out infection/ neoplasia
What infectious disease should you screen for when you see IMTP?
- Tick borne disease: Ehrlichiosis, Rocky Mountain Spotted Fever, Anaplasmosis, Histoplasmosis
- Leishmaniasis
- Canine distemper virus
Leishmaniasis
Canine Leishmaniasis
How many platelets should you see per high power field? What breed might this be different in and how?
5 platelets per HPF
Healthy greyhounds can have lower platelet concentrations than other breeds
Acute treatment of IMTP
- Transfusion will not raise platelet count but may help anaemia
- Vincristine 0.5-0.7mg/m2 once may induce thrombocytosis within severe days
Long term treatment of IMTP
- Immunosuppression
- Agent of choice = prednisolone; majority of dogs show increased platelet count within 7 days
- Other immunosuppressive agents only needed if significant side effects with prednisolone. Options: azathiorpine, cyclosporin, mycophenolate mofetil, leflunomide
How can IMTP cause death?
- Severe life-threatening haemorrhage. GIT common site for major bleeds
- Small but catastrophic bleed in CNS or lung.
Platelets
Prognosis and follow up for IMTP
- Minimum duration of therapy: 4-6 months
- Immunosuppressive medication tapered slowly
- Long-term mortality 10-15%
- Relapse 9-40%
- Poor prognostic indicators: melaena, high BUN
Which of the following factors would be most likely to predispose a dog to a primary immunodeficiency disorder?
a) genetics
b) environmental factors e.g. stress
c) infection e.g. canine parvovirus
d) immunosuppressive doses of glucocorticoids
e) increasing age
a) genetics
Which of the following findings is most sensitive for a diagnosis of IMHA?
a) saline agglutination test
b) low PCV
c) Coombe’s test/ Direct Antigen Test (DAT)
d) spherocytes
e) anaemia with hepatomegaly
Most sensitive = least likely to get false negative
c) Coombe’s test/ Direct Antigen Test (DAT)
What would be the primary indication for blood tranfusion in a stable anaemic cat (PCV 24%) following an RTA?
a) PCV not increasing after 24hrs
b) PCV at 22% or below
c) Gums getting more pale
d) Cardiovascular compromise or deterioration
e) Development of hypothermia
d) Cardiovascular compromise or deterioration
When should you give a blood tranfusion?
