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3. Cat & Dog > Immune mediated disease Pt. 1 > Flashcards

Immune mediated disease Pt. 1 Flashcards

1
Q

what is a primary immune mediated disease?

A

Primary (non-associative):
* Defect in immune tolerance
* Antibodies against self

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2
Q

what is a secondary immune mediated disease?

A

Secondary (associative):
* Non-self antigens ➔ normal cell membrane
> Antibodies ➔ non-self antigens
* Abnormal immune stimulation
* Possible causes: drugs, inflammatory disorders, infection, neoplasia, etc

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3
Q

IMHA - what is it, generally? what types are there?

A
  • Destruction of RBCs
  • Primary or secondary IMHA
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4
Q

IMHA - what type of anemia do we see?

A
  • Regenerative anemia (more common):
    > RBCs in circulation lysed
  • Non-regenerative anemia:
    > RBC precursors at bone marrow level destroyed
    > “Precursor immune mediated anemia” or PIMA
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5
Q

Primary IMHA: Signalment

A
  • Anyage,any breed
  • Predisposed:
    > American Cocker spaniels, Bichon, poodles, Old English sheepdogs, collies
    > Most 2-7 years of age
    > Females > males
    > Spring & summer (?)
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6
Q

IMHA: Patient Presentation

A

Clinical signs related to severity of anemia:
* Lethargy, weakness, anorexia
* Collapse
* Tachypnea
* Vomiting, diarrhea
* “Dark” urine (bilirubin, hemoglobinuria)

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7
Q

IMHA: Physical Examination common findings

A
  • Pallor (majority of cases)
  • HighHR&RR
  • Enlarged spleen, liver (25-50% of cases), abdominal discomfort
  • Icterus
  • Pigmenturia
  • Hemic murmur
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8
Q

Common mechanisms causing anemia

A
  1. blood loss
  2. lack of production
  3. hemolysis
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9
Q

initial tests for dog presenting with anemia

A
  • Complete blood count**
  • Serum biochemical profile
  • Urinalysis
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10
Q

why can we sometimes see Mildly elevated ALT in light of marked anemia

A
  • Hypoxic injury to hepatocytes?
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11
Q

why can we sometimes see elevated bilirubinemia and bilirubinuria in light of marked anemia

A
  • Hemolysis
  • Hypoxic liver injury
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12
Q

IMHA: Diagnosis

A

Anemia
* Hct usually <0.25-0.30 L/L
* (Normal ~0.39-0.50)

Evidence of Ab’s against RBCs:
* + Autoagglutination
* + Coomb’s test
* Spherocytosis (80-90%)

Evidence of hemolysis
* Icterus
* Hemolytic serum/urine

Autoagglutination

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13
Q

what is RBC autoagglutination in IMHA? when can we observe it / with what tests?

A
  • May be observed grossly
    > In the tube
  • Slide agglutination test
    > Saline to blood 1:49 ratio
    > 1 drop EDTA blood
    > Check for macro and microscopic agglutination
  • Slide agglutination test not well standardized
    > Some argue it isn’t helpful in the overall case work-up and you’re better off examining the blood smear instead
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14
Q

what is the coomb’s test? what does it look for?

A

For IMHA
* Detects Ab or complement on RBC surface
* “Coomb’s reagent”
> Anti-canine IgG, IgM, complement
> Added to washed RBCs
> Detect specific RBC agglutination

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15
Q

Spherocytosis - how does it arise? what does it suggest?

A
  • RBC has antibodies on surface
  • Recognized by macrophages in spleen or liver
    > Phagocytized
    > Partial RBC membrane defect
  • Highly suggestive of IMHA
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16
Q

IMHA: Extravascular vs Intravascular Hemolysis
- what do we see? what is more common and severe?

A

Extravascular (more common, less severe):
* RBC’s degraded in splenic/hepatic macrophage > Spherocytes
* Hemoglobin released within macrophages
> Processed ➔ bilirubin ➔ icterus

Intravascular:
* RBC’s lysed in circulation
* Hemoglobin released ➔ hemolytic serum, urine

()()()

Both intra and extravascular hemolysis can occur in some IMHA patients

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17
Q

How many criteria needed for diagnosis of IMHA? what is ‘suspicious’?

A

“Diagnostic” for IMHA:
* Anemia,
* At least 2 signs of destruction (spherocytes, Coombs, SAT)
* And at least 1 sign of hemolysis (icterus, hemolytic serum, urine)

“Suspicious” for IMHA:
* Anemia
* 1 sign of destruction
* 1 sign hemolysis
* No other causes of anemia identified

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18
Q

How and when to rule out secondary IMHA?

A

Once supportive evidence of IMHA found, consider ruling out secondary causes:
* Client interview to review previous medical history
* Infectious agents – 4Dx snap test, serology depending on area
* Imaging for neoplasia, infections, inflammation
> Thoracic radiographs
> Abdominal ultrasound

19
Q

infectious causes of secondary IMHA

A

Anaplasma
Babesia
Mycoplasma
Heartworm

20
Q

drug causes of secondary IMHA

A

Sulfas
Beta lactams
Certain toxins

21
Q

when can we see direct hemolytic anemia (not immune mediated)

A
  • Zinc ingestion (some pennies, toys, diaper
    cream, dog tags)
  • Hypophosphatemia
  • Onion & garlic
  • Acetaminophen

> check patient history to rule out

22
Q

IMHA: Treatment goals

A
  • Stabilize the patient
  • Stop the immune-mediated destruction
  • Prevent complications
    > Thromboembolism
23
Q

Initial Stabilization strategies for IMHA if we see Signs of dehydration, hemodynamic instability?

A

> IV catheter, start IV fluids

24
Q

“Transfusion triggers” or signs of
insufficient oxygen delivery

A

> Tachycardia, tachypnea, increased work breathing
Dull mental attitude
Very marked anemia

25
Q

Immunosuppressive Medications that can be used for IMHA

A
  • Few studies with high quality evidence to inform clinicians

Corticosteroids:
* Used alone will result in successful outcome for many patients
* No good consensus if/when a second-line immunosuppressive should be added

26
Q

IMHA: Combination Therapy benefits and risks?

A

Possible benefits:
* Improved survival (?)
* Better treatment for more severe cases(?)
* Ability to wean corticosteroid earlier

Risks:
* Side effects of medications
* Increased risk of secondary infections
* Overall lack of evidence

27
Q

Mainstay of IMHA treatment? how fast does it work?

A

Corticosteroids
* Can see improvement within 7 days
* Single-agent treatment often sufficient
* Common options:
* Prednisone @ 2 mg/kg PO q24h
* Dexamethasone @ 0.25 mg/kg IV q24h

28
Q

Corticosteroids pros and cons

A

PROS:
* Inexpensive, available
* Rapid onset of action
* Several mechanisms of impairing the immune system

CONS:
* PU/PD, polyphagia
* Panting
* Muscle wasting
* Gastric ulceration
* Immunosuppression

29
Q

Azathioprine - what does it do?

A
  • Antimetabolite
  • Inhibits T cell proliferation
30
Q

Azathioprine - potential side effects? when not to use? requires what?

A
  • GI upset
  • Pancreatitis
  • Liver toxicity
  • Bone marrow suppression
    > Especially cats – do not use
  • Requires regular monitoring of bloodwork
31
Q

Cyclosporine - what does it do? does it work for IMHA?

A
  • Inhibits T-cell function
  • Anecdotal efficacy, expensive
  • Ideal to monitor [drug] levels
  • Note: different dose / frequency than for skin disease
32
Q

Cyclosporine side effects

A
  • GI upset
  • Alopecia
  • Gingival hyperplasia
  • Opportunistic infections
  • Neoplasia (?)
33
Q

Mycophenolate - what does it do, what patients is it used in?

A
  • Inhibits T- and B-lymphocyte production
  • Used in dogs or cats
34
Q

Mycophenolate adverse effects?

A
  • Diarrhea most common
35
Q

Mycophenolate advantages over azathioprine:

A
  • Lack of myelosuppression or hepatotoxicity
36
Q

what % of canine IMHA patients develop thromboembolic complications? pathogenesis?

A

Up to 80% canine IMHA patients develop thromboembolic complications
* Pathogenesis unknown
> Activated platelets
> Disseminated intravascular coagulation

37
Q

Thromboprophylaxis Options

A

Platelet inhibition
* Clopidogrel
* Low dose aspirin (less effective than clopidogrel, typically no longer used alone)

Anticoagulants
* Heparin
* Rivaroxaban

Usually just use one of the above options

38
Q

overall example treatment plan for IMHA

A
  • Stabilize the patient
    > IV Fluid therapy (dehydration / not eating), monitor for transfusion triggers
  • Immunosuppression
    > Dexamethasone IV or prednisone PO if
    taking oral meds
  • Prevent TE complications
    > Clopidogrel PO
39
Q

IMHA chronic treatment - how to manage

A
  • Decrease 1 immunosuppressive at a time
    > Often prednisone first (due to PU/PD, etc) if there are >1 immunosuppressives
  • Recommend decreasing 1 med by ~25-50%, every 2-4 weeks
40
Q

IMHA: Relapses rate?

A
  • Relapse rate ~15-30%
41
Q

when treating IMHA for the long term, what do we do if Hct has declined compared to last recheck:

A
  • Back to previous doses when Hct was normal
  • Check Hct frequently (1x/week depending on patient’s condition)
  • May need to increase back to full immunosuppressive doses
  • Can try tapering more slowly once normal Hct again
  • Some need chronic medication for life
    > Usually low-dose
42
Q

Canine IMHA:
Prognosis

A
  • Overall, guarded to poor prognosis for long-term survival
  • 50% or more mortality rate in some studies
    > Referral bias?
  • Majority of deaths/euthanasia within first 2 months
    > Ongoing disease
    > Complications
43
Q

Canine IMHA: treatment Summary

A
  • Supportive care (e.g., transfusion, ICU if
    needed)
  • Immunosuppression (steroid +/- other agent)
  • Anti-thrombotics

3. Cat & Dog (33 decks)

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