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ACVIM Reading List > Immune Mediated Disease Literature > Flashcards

Immune Mediated Disease Literature Flashcards

1
Q

In healthy SCWT, what has been noted to be increased in animals that have siblings with PLE/PLN?

A

• High prevalence of perinulcear antineutrophilic cytoplasmic autoantibodies (pANCA) in healthy Wheatens (21%)
○ Significantly association of + pANCA and diagnosis of PLE or PLN in sibling

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2
Q

Did immunosupression have an effect on Coomb’s?

A

NO!

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3
Q

Did storage have an effect on Coomb’s?

A

NO! Samples were stored chilled for up to one week!!!

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4
Q

Did blood transfusion have an effect on Coomb’s

A

NO! Did NOT result in a false + result

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5
Q

What is a sensitive and specific test for IMHA that is resilient to storage, immunosuppression, and transfusion artifacts?

A

Coomb’s (DAT - Direct Antiglobulin Test)

Sn: 50-89%

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6
Q

How often can blood donors donate blood?

A

• Donors >27 kg can donate 450 mls (16 ml/kg) every 3 weeks without experiencing adverse effects

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7
Q

How long can you store fresh whole blood and have the platelets still work?

A

About 72 hrs

Just don’t chill = KILLS platelets

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8
Q

If you give 10 ml/kg of fresh whole blood, how much will this increased your platelet count?

A

About 10K

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9
Q

If you give 1 unit of platelet rich plasma, how much will this increase your platelet count?

A

Max 40K

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10
Q

What happens to thrombocytopenia patient’s vessels over time?

A

Platelets are important for plugging gaps in endothelium - over time thrombocytopenic patients get “gaps” / thinning in their vessels

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11
Q

What did feline idiopathic pure red cell aplasia respond to?

A

Steroids and cyclosporine
MST: 31-406 d
Relapse common
But 4 cats went into remission

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12
Q

What composes IVIg?

A

90% biologically intact IgG (little IgA, IgM, CD4, CD8, human leukocyte antigen)
T1/2: Dogs 7-9 days

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13
Q

What is the MOA of IVIg?

A

○ Blocks Fc receptors, eliminates pathogenic autoantibodies, modulate cytokine synthesis, inhibit complement, mediate Fas-Fas ligand interactions

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14
Q

What are the uses of IVIg in vet med?

A

§ Use in vet med: IMHA, ITP, pemphigus foliaceus, SARDS, myasthenia gravis, cutaneous disease

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15
Q

What are adverse events with IVIg?

A

Type I hypersensitivity/anaphylaxis; hypercoagulation (TED), renal failure, hypotension, pseudohyponatremia

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16
Q

What had an effect on the plasma concentrations of prednisolone in healthy dogs?

A

• Modulation of P-glycoprotein expression influenced plasma concentrations of prednisolone PO (healthy beagles)
○ Rifampicin (induce P-gp) - Upregulated duodenal P-gp in dogs and reduced AOC of pred
○ Ketoconazole (inhibitor of P-gp) - Downregulated expression of duodenal P-gp and increased AOC of pred

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17
Q

What could be used to monitor immunosupression with cyclosporine?

A

Flow cytometery: • Direct T cell function (flow for IL-2, IL-4, IFN-gamma) may be effective/more sensitive to monitor immunosupprressive tx with cyclosporine in dogs
○ Low dose (5 mg/kg PO q24hrs): Significant decrease in IFN-gamma but IL_2 was unaffected
○ High dose (10 mg/kg PO q12hrs): Significantly decreased IL-2 and IFN-gamma, but NOT IL-4
○ T-cell function is suppressed at trough blood concentrations >600 ng/ml, at least partial suppression at lower doses

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18
Q

What effects do high doses of methylprednsiolone have on neutrophils?

A

• High doses of methylprednisolone (MPSS) suppressed major functions of neutrophils (including adhesion markers CD11b, CD18; decreased phagocytosis; reduction in oxidative burst) for at least 7 days after tx

No significant change in migration noted

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19
Q

Is transdermal cyclosporine recommended in cats?

A

NO! Inconsistent absorption

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20
Q

For IMHA patients, what is superior: aspirin. plavix, or both?

A

No difference in survival btwn groups in survival = All about 13% mortality and TED about 13%

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21
Q

For IMHA patients, what is superior: constant dose heparin or individually dosed heparin?

A

% mortality and incidence of TED significantly different btwn groups
MST: Constant heparin 68d vs individual dosed heparin >180 d

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22
Q

For IMHA patients, was plasma helpful for preventing TED?

A

No difference btwn groups (all dogs were on heparin too)

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23
Q

Why should we not call it “Evan’s syndrome”?

A

Since we cannot rule out IM process, bystander effect, vs onset of DIC

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24
Q

Which is better for IMHA, azathiaprine, cyclosporine, or cyclophosamide?

A

No evidence of azathiaprine vs cyclosporine

DO NOT use cyclophosamide

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25
Q

Did IVIg result in improved survival in IMHA dogs?

A

NO! But it did improve hematologic parameters

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26
Q

What antithrombotics were associated with improved survival in IMHA?

A

Individually dosed heparin and low dose aspirin

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27
Q

What are the major prognostic indicators in IMHA dogs?

A

Bilirubin and BUN (>56)

Others: 				□ Spherocytosis
				□ Sex (male)
				□ Season (warm)
				□ PCV (0.23 mg/dl
				□ Monocytes >100/ul
				□ aPTT
				□ IL-18

MCP-1

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28
Q

Is there a seasonality to IMHA?

A

Yes

Reported: ○ More cases in spring and summer at the San Diego office NOT true for LA practice

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29
Q

Can mycophenolate be used for IMHA?

A

Yes! - Reported in dogs and cats
• Mycophenolate in dogs with IMHA did result in remission BUT also horrible GI -toxicity (10-15 mg/kg PO q8hrs, HIGH DOSE)
○ In combination with pred and low dose aspirin (20.5 mg/kg/day)

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30
Q

What has been shown with using lactate in IMHA patients regrading prognosis?

A

lactate concentration at presentation was significantly higher in nonsurvivors than survivors
○ Serial lactate was a better measure (more predictive), If persistent hyperlactemia at 6 hours after admission they were less likely to survive
§ Optimal lactate cut off 4.4 mol/l (correctly predicting outcome 73%, sen 60%, spec 77%)
§ All dogs with lactate that normalized within 6 hrs survived, only 71% with high lactate at 6 hrs survived

Overall survival: 77%, 20% euthanized, 3% died

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31
Q

What is the prognosis of IMHA when there is severe thrombocytopenia (

A

○ Similar survival to either disease alone (75% survived and 25% euthanized)
○ Younger dogs were more likely to survive

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32
Q

What should pANCA not be used as a biomarker of IBD?

A

• Perinuclear antineutrophilic cytoplasmic autoantibodies (pANCA) were detected in a IMHA dogs (47%) and dogs with vector borne disease (48% esp if titer for Leishmania infantum), and 5% in healthy dogs
○ pANCA is a non-specific marker and should NOT be used for IBD
○ May be a biomarker of IM or infectious diseases

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33
Q

Based on TEG what do IMHA look like?

A

Hypercoag!! Even before pred given

34
Q

What has been associated with more severe more severe degree of anemia, spheocytosis, and autoagluttination in IMHA dogs?

A

• Dogs with IMHA with ≥ 2 Ig isotype bound to RBCs (IgG and IgM) are likley to have more severe degree of anemia, spheocytosis, and autoagluttination
○ Lower HCT if IgG AND IgM compared to only one isotype

More spherocytes if IgG AND IgM compared to only IgM

35
Q

Have IgA antibodies been reported in dogs with IMHA?

A

YES! One case

36
Q

What is true regarding the cytokine profile in IMHA dogs?

A

• Mixed cytokine response in IMHA dogs: Marcophage/moncyte activation and recruitment increased in nonsurvivors (IL-15, Il-18, GM-CSF, MCP-1)
○ Increased Il-18 and MCP-1 were independently associated with mortality (prognostic indictors)

37
Q

Which cytokines when elevated have been related to a poor prognosis with IMHA?

A

Increased Il-18 and MCP-1

38
Q

What is true regarding platelets in IMHA patients?

A

• Dogs with IMHA have increased platelet activation (based on flow cytometry) - Even more activated if thrombocytopenia noted with IMHA

39
Q

Which spp with IMHA is more like to have persistent cold autoagglutination and Coomb’s + at 37C with polyvalent antiserum?

A

CATS wth IMHA

40
Q

What combination has been shown in dogs to improve outcome with IMHA?

A

Steroids, azathioprine, and ultra-low dose aspirin (Weinkle study)

41
Q

What are microparticles?

A

• Membrane derived from many cell types that are released into circulation
○ Budding of phospholipids secondary to disruption of phospholipids
○ Can express antigen, cell surface proteins, cytoplasmic content, and nuclear components

Release can be physiologic or pathogenic

42
Q

What makes microparticles proinflammatory and procoagulant?

A

Active phospholipids on outer leaflet

43
Q

How did lyophilized platelets compare to fresh platelet concentrate in bleeding ITP dogs?

A

no difference in transfusions needed, hospital time, survival to d/c or 28 days
○ Very small sample size!!! But low adverse reactions

44
Q

What are the two big prognostic factors in dogs with ITP?

A

Melena and high BUN

45
Q

In dogs with ITP what was related to needing more tranfusions?

A

Melena

46
Q

What can be monitored in dogs with ITP that changes prior to plt count?

A

PCT may be used to monitor ITP dogs
○ Time to achieve PCT (estimate of platelet mass, threhold = 0.07575) was shorter than for seeing platelet count (threhold 75k) (3 vs 4 days)

ITP dogs had increased MPV compared to controls

47
Q

How did IVIg compare to vincristine in ITP Dogs?

A

No difference btwn groups at discharge, 6 months, or 1 year

○ Median platelet recovery time: 2.5 days

48
Q

What was the mean platelet recovery time for IVIg and vincritsine in dogs with ITP?

A

○ Median platelet recovery time: 2.5 days

§ Previous studies (IVIg 3.5 days and vincristine 4.5 days)

49
Q

What is recommended IVIg or vincirstine for ITP dogs?

A

No difference btwn groups at discharge, 6 months, or 1 year
○ Median platelet recovery time: 2.5 days
○ Cost of tx higher in IvIg group ($4100) compared to vincristine ($2400)
§ Since vincristine is CHEAPER they are recommending this over IVIg

50
Q

Within 42 days is there an association of ITP with vaccination?

A

NO!
• No association btwn idiopathic ITP and recent vaccination (within 42 days)
○ ITP (48) 8 % vs controls (96, age matched) 14%

51
Q

Which drug has been used as a sole agent in ITP dogs and has resulted in complete remission?

A

Mycophenlate

52
Q

What in IMPA dogs has been correlated with median pain score, joint cellularity, and mobility (accelerometry)?

A

• C-reactive protein higher in IMPA dogs (>75 ug/ml) compared to controls Might be able to use for monitoring, instead of joint taps
○ Significantly lower at 2 weeks and even lower at 4 weeks of tx
○ Correlated with median pain score, joint cellularity, and mobility (accelerometry)
○ Normal CRP in dogs with OA

53
Q

Which cytokines did not correlated well with CS, joint cellularity for IMPA dogs?

A

§ Plasma IL-6 higher in IMPA dogs compared to controls
□ Lower at week 4 of tx but only modest correlation with pain scores

CXCL8 (IL-8) did NOT differ btwn IMPA and healthy dogs

54
Q

What immunosuppressive has been evaluated in dogs with IMPA and how did it do?

A

• Lefluonmide (3-4 mg/kg PO q24hrs) was used to tx IMPA in dogs, recommend tx for 6 weeks prior to changing
○ Changes based on cytologic joint eval and CS
○ 8/14 complete remission, 5 partial remission, 1 minimal response

55
Q

What is seen in sled dogs after racing in regards to Ig?

A

• Sled dogs racing long distance had a substantial decrease in [IgG] (training and racing) and IgM and IgE - Hypogammaglobulinemia after racing (32% dogs)
○ Compared to 18% before race and 24% 4 months after race

56
Q

What is the reading on a serum protein electrophoresis called?

A

Densitometer

57
Q

In cats with serum protein electrophoresis performed, what is the most common finding?

A

Polyclonal gamma globulins = Most related to infectious causes
39/80 dx with FIP!!!

58
Q

What is a potentially rare adverse fatal complication of phenobarbitol?

A

Dysmyelopoiesis

59
Q

What are the common bloodwork changes with starvation?

A

Hypoalbuminemia, thrombocytosis, anemia, increased BUN, elevated BUN/crt ratio, and hypocalcemia
○ Dogs with anemia and hypoalbuminemia may need more time to gain weight

60
Q

In the Wachtehund, what def is noted and what are CS?

A

• Phosphofructokinase deficiency seen in Wachtelhund (exercise intolerance, hemolytic anemia, pigmenturia)

NOT same mutation (muscle type PFK M-PFK gene) as in Springers, Cockers, Whippets, Mixed breeds

61
Q

What is congenital methemoglobinemia and how is it tx?

A

• Congenital methemoglobinemia in dog dt cyctochrome B5

Treated with methylene blue

62
Q

In dogs with regenerative anemia is macrocytic hypochromic that most common finding?

A

NO!!! Moderate accuracy 70%

63
Q

What is a the best predictor of regenerative anemia in dogs?

A

○ Polychromasia +/- high RDW were more accurate (77% poly only and 79% poly + high RDW)

Compared to High MCV and Low MCHC = Moderate accuracy for detecting regeneration (70%, sen 11, spec 98)

64
Q

Is regenerative or nonregenerative anemia more common in cats?

A

Anemia in cats (1,098): Most were nonregenerative (58%) vs 43% for regenerative

65
Q

Can you use the RBC indices to detect regeneration in cats?

A

NO! ○ Erythrocyte indices were NOT sensitive for regeneration (high MCV/low MCHC: Sen 20%, spec 91%)

66
Q

In cats, is the severity of the anemia associated with prognosis?

A

NO! BUT, was with etiology of anemia and classification of disease
§ More likely to survive if hemolysis (than BM dz) and IM dz (than neoplasia)

67
Q

What is true regarding cats with degenerative left shifts?

A

1.57X more likely to die or be euthanized in hospital than cats w/o degenerative left shift
○ Increasing severity of left shift is associated with increased likelihood of death or euthanasia
○ Over 20 days after admission
○ Also FeLV infected cats were >3 fold higher hazard of death/euthanasia compared to noninfected cats
○ Purebreeds lower risk of death

68
Q

What is true regarding dogs with degenerative left shifts?

A

significant predictor (2 fold) of death or euthanasia but it was related to disease state and should be used with caution
○ Age also strong predictor
○ Did NOT detect a trend in severity of left shift and hazard of death/euthanasia

69
Q

Were increasing severity of degenerative left shift associated with hazard of death in dogs and cats?

A

In cats YES

In dogs NO!

70
Q

What is a better method of DEA 1.1 typing in patients with IMHA?

A

○ Errors in patients with IMHA

§ Immunochromatographic cartridge may be better for typing animals with agglutination present

71
Q

Which disease in cats results in discordant blood typing?

A

FeLV

72
Q

Does hyperbilirubemia result in changes in total protein obtained by refractometry?

A

NO!
Did NOT interfere with refractometric estimate of total protein (up to 41.5mg/dl bilirubin)
○ Some variation with total proteins related to method of conversion of refractive index to total protein concentration, NOT bilirubin concentration!

73
Q

Can sedation in cats affect CBC and chem results?

A

YES! But not that are clinical relevant

74
Q

In ill cats, what is a common finding on chemistry that is related to longer hospital stays, more cost, and higher mortality? Can it be used to predict outcome in cats?

A

CK
• Increased CK (creatine kinase) is very common in ill cats (60% samples): Cats with increased CK longer hospitalization, more expensive costs and high mortality
○ BUT CK was inaccurate outcome predictor in cats

75
Q

What is Scott Syndrome?

A

• GSD with hemorrhage consider canine Scott Syndrome (platelet procoagulant deficiency)
○ No petechia noted
○ Most responded to platelet transfusion

76
Q

When can you see a contraction alkaloids?

A

Dt fluid loss = Volume contraction (esp if from vomiting)

77
Q

Do sled dogs have iron def after racing?

A

Unlikely only 4% had low ferritin

BUT detection of it was inhibited by presence of inflammation (high ceruloplasmin and CRP)

78
Q

What are risk factors of peri-op death for dogs with splenic masses?

A

• Marked pre-op thrombocytopenia, anemia, and intra-op ventricular arrhythmias were RISK factors for pei-op death in dogs with splenic masses
○ 8% died: Thrombotic or coagulatopathic syndromes, bleeding mets
○ Every 10K decrease in platelets = Increased odds of death by 6%
○ OCV 30%
○ Intra-op arrhythmias odds of death twice those that did not have arrhythmias

79
Q

What infectious disease has been isolated from splenic masses?

A

Bartonella DNA higher prevalence in fibrohistiocytic nodules (30%) and HAS (26%) in dogs compared to lymphoid nodular hyperplasia (10%) and controls (0%)
○ Babesia and hemotrophic Mycoplasma DNA were significantly lower than Bartonella
○ No difference in 3 infectious dz and lymphoid nodular hyperplasia

80
Q

What can a higher mean mass to spleen volume ratio AND higher splenic weights as % body tell you about splenic masses in dogs?

A

• Dogs with benign splenic masses significantly higher mean mass to spleen volume ratio AND higher splenic weights as % body than dogs with HSA

ACVIM Reading List (27 decks)

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