Immune mediated disease Pt. 1 Flashcards by Mark Sunarich

what is a primary immune mediated disease?

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

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what is a secondary immune mediated disease?

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

Destruction of RBCs
Primary or secondary IMHA

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IMHA - what type of anemia do we see?

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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Primary IMHA: Signalment

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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IMHA: Patient Presentation

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

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IMHA: Physical Examination common findings

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

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Common mechanisms causing anemia

blood loss
lack of production
hemolysis

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initial tests for dog presenting with anemia

Complete blood count**
Serum biochemical profile
Urinalysis

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

Hypoxic injury to hepatocytes?

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

Hemolysis
Hypoxic liver injury

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IMHA: Diagnosis

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

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

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

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

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

“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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How and when to rule out secondary IMHA?

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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

infectious causes of secondary IMHA

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Anaplasma
Babesia
Mycoplasma
Heartworm

drug causes of secondary IMHA

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Sulfas
Beta lactams
Certain toxins

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

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

> check patient history to rule out

IMHA: Treatment goals

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Stabilize the patient
Stop the immune-mediated destruction
Prevent complications
> Thromboembolism

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

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> IV catheter, start IV fluids

“Transfusion triggers” or signs of
insufficient oxygen delivery

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

Immunosuppressive Medications that can be used for IMHA

- 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

IMHA: Combination Therapy benefits and risks?

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

Mainstay of IMHA treatment? how fast does it work?

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

Corticosteroids pros and cons

PROS: * Inexpensive, available * Rapid onset of action * Several mechanisms of impairing the immune system CONS: * PU/PD, polyphagia * Panting * Muscle wasting * Gastric ulceration * Immunosuppression

Azathioprine - what does it do?

* Antimetabolite * Inhibits T cell proliferation

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

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

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

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

Cyclosporine side effects

* GI upset * Alopecia * Gingival hyperplasia * Opportunistic infections * Neoplasia (?)

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

* Inhibits T- and B-lymphocyte production * Used in dogs or cats

Mycophenolate adverse effects?

* Diarrhea most common

Mycophenolate advantages over azathioprine:

* Lack of myelosuppression or hepatotoxicity

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

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

Thromboprophylaxis Options

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

overall example treatment plan for IMHA

* 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

IMHA chronic treatment - how to manage

* 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

IMHA: Relapses rate?

* Relapse rate ~15-30%

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

* 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

Canine IMHA: Prognosis

* 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

Canine IMHA: treatment Summary

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

Immune mediated disease Pt. 1 Flashcards

(43 cards)