Immune Mediated Ettinger Flashcards

1
Q

What are 5 mechanisms of loss of self tolerance?

A
  1. Release of sequestered antigen or expression of developmental antigen
  2. Abnormal tolerance (changes in T reg)
  3. Molecular mimicry, cross reactivity to foreign antigen
  4. Alterations in self proteins (haptenization - sulfas in dobies)
  5. Oxidation damage
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2
Q

What % of normal dogs and cats have a + ANA?

A

Dogs: 20%
Cats: 10%

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3
Q

What is the platelet factor 3 test?

A

Patient plasma with normal platelets and then check PT

If PT shortened, Igs injured plts and released phospholipids = coag activation

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4
Q

Which 2 infectious diseases can results in antiplatelet antibodies?

A

RMSF and Ehrlichia (+ based on flow)

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5
Q

How do you diagnose SLE?

A

Need Class I +2 of class 2 or 3+ of Class 2/3
Class 1: ANA +
Class 2: Polyarthritis, nephropathy, proteinruia, IMHA, dermatopathy, petechia, pleuritis-pericarditis, cutaneous lesions
Class: 3 LN, anemia, fever

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6
Q

What is the LE Cell test?

A

Test for SLE
Clotted mashed blood (release nucleoproteins), incubated with neutrophils
If Abs - neuts will phagocytze the material

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7
Q

What is the prognosis for SLE?

A

Unknown!!

Make to monitor renal function in these patients

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8
Q

What are autoantigens in primary IMHA?

A

RBC glycoproteins
RBC anion channel band 3
Cytoskeletal protein spectrin

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9
Q

What are the most common Ig in IMHA?

A

IgG >IgM
Most only IgG, some IgG and IgM, rare to have IgM only
1 report of IgA

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10
Q

What happens if you have IgG in IMHA?

A

Extravascular hemolysis from phagocytes of RES, partial internalization = spherocytes

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11
Q

What happens if you have IgM in IMHA?

A

Intravascular hemolysis that is complement mediated and also Extravascular hemolysis

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12
Q

What is the most common form of IMHA in cats?

A

Secondary

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13
Q

What % of dogs with IMHA get TED?

A

About 30-50%

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14
Q

Why are IMHA dogs hypercoaguble?

A

Increased in TF (esp MP)
Increased fibrinogen
Increased platelet response (75% have activated platelets, increased P-selectin)
Decreased anticoags (AT, thrombomodulin, Protein C, plasminogen activators)

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15
Q

What are the risk factors for TED in IMHA?

A
Severe thrombocytopenia
Hypoalb
Neg Coombs
IV catheter
Increased ALP
Hyperbilirubinemia
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16
Q

What are the hallmarks for dx of IMHA?

A

Marked regenerative anemia - 42-85%
Spheocytosis - 52-95%
Autoagglutination (Anti-RBC Abs)

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17
Q

What are options if there is a ineffective erythroid regeneration?

A
  1. IM destruction and erythroid precursor
  2. Anemia of inflammation
  3. Paraneoplasia
  4. Lack of EPO (CKD)
  5. BM disease (myelophtisis, myelofibrosis, myeloproliferative disease)
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18
Q

Can Anti RBC Abs be seen in ITP dogs too?

A

YES

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19
Q

What is contained in the Coomb’s antiserum?

A

Species specific Antiserum - IgG, IgM, C3

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20
Q

How often is IMHA coomb’s negative?

A

23-63%

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21
Q

Is Ig isotype associated with survival in IMHA?

A

No, but bilirubin is!!

If you have >2 Ig isotypes (IgG/IgM) = More severe anemia, spheocytosis, and autogluttination

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22
Q

Is the # of transfusions a predictor of survival in IMHA?

A

Yes it has been noted

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23
Q

What is the thought behind HIGH dose pulse steroid tx for IMHA?

A

Nongenomic effects that result in PROFOUND supression

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24
Q

What is the cytotoxic component of azathioprine?

A

Thioguanines Resulting in impaired RNA, DNA, and protein synthesis

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25
How much more potent is mycophenolate to azathioprine?
10X
26
When would clodronate have the most benefit in IMHA dogs?
It results in MP depletion (spleen) - Most benefit if IgM or C3 = Intravascular hemolysis (?)
27
What is the long term survival in IMHA?
About 40%
28
What is the mortality rate with IMHA?
About 30-70% - High early moratality in first 2 months
29
Which cytokines are related to poor outcome in IMHA?
IL-15, IL-18, GM-CSF, MCP-1
30
Can feline IMHA be nonregnerative?
YES the majority of them are >58%
31
What is the prognosis for feline IMHA?
Mortality 24-32% | Dt Lower TED
32
What is the classic presentation of phosphofructokinase def?
Persistent compensation hemolytic anemia = CRISIS with exertion "Alkaline fragile"
33
What is the prognosis with PK def?
``` Pyruvate kinase defs = Decrease in ATP = Membrane defect = HEMOLYSIS IRON Overload (changes in BM and liver) Dead by 1-5 yrs!!! ```
34
How does hypophosphatemia result in hemolysis?
Decreased ATP, depleted 2-3DPG, and ecreased glutathione - RBC fragility = Hemolysis
35
What the compensatory mechanisms dt anemia?
From hypoxia from decreased Hbg 1. Increased 2,3 DPG (only in dogs) 2. Increased CO
36
Which breed gets hemophagocytic syndrome?
Tibetan Terriers - NOT cancer, but proliferative disorder of MPs = Bi and Panyctopenias
37
How is vincristine helpful in ITP?
Increased platelet count by stimulating megakaryotyes and impairs phagocytosis of opsonized platelets by impairing mirotubules within MP!!!
38
What results in GI signs with leflunomide?
Accumulation of metabolite TMFA
39
Is the severity of thrombocytopenia prognostic?
NO | lowest with sepsis and ITP
40
How do you obtain a platelet count?
plt in HPF and X15-20K = Average platelets
41
Why do CKCS have a macrotrhombocytopenia?
Related to a Beta tubulin defect
42
What is the primary antibody in ITP?
IgG - Against alpha granules or GPIIb-IIIa
43
What are the 3 main products for platelet replacement?
1. Fresh Whole Blood 2. Platelet rich plasma 3. Platelet concentrate
44
What does vWF bind to on platelet?
GPIb alpha receptor
45
Are there daily variations in vWF concentrations?
Yes, may need to check more than once
46
Is there an association of HypoT4 with vWD?
NO!!
47
What is the treatment of vWD and what is the drugs MOA?
Desmopressin - Release stores vWF from endothelial cells | Enhanced platelet function independent of vWF
48
What products have vWF if you have a patient that is bleeding?
1. Fresh Whole Blood 2. FFP 3. Cryoprecipitate (5-10X vWF in 1/10 volumes) NOTE: No improvemetn in Fresh plasma in BMBT
49
Are Hageman Factor Def cats at risk of bleeding and can they undergo procedures?
Factor 12 - Prolonged PTT | No bleeding and safe to undergo procedures
50
What factors is stores blood lacking?
No factor 8, vwF, or 5 | But it has Vit K factors (2,7,9,10)
51
What should you consider if you have low plt count and normal coags?
Thrombocytopenia
52
What should you consider if you have normal plt count, and just PTT is prolonged?
1. Intrinsic Factor Defects (8, 9, 11) | 2. Contact Pathway Factors: Hageman, prekallikrein, kininogen
53
What should you consider if you have normal plt count and prolonged PT?
1. Extrinsic Factor Defects (7)
54
What should you consider if you have normal plt count and prolonged PT/PPT?
1. Common Pathway (2, 5, 10) | 2. Combined Vit K (2,7,9,10)
55
What should you consider if you have normal plt count and prolonged PT/PTT, and low fibrinogen?
Fibrinogen def
56
What should you consider if you have normal plt count and normal coags but bleeding?
vWD Platelet defects Firbinolysis defects Nonhemostatic defects
57
What are the major factors that result in hypercoagulability?
1. Decreased endogenous anticoagulants (AT, protein C, protein S) 2. Increased enzymatic activity (increased activity of Factor 8 with Cushing's) 3. Increased fibrinogen (inflammation, more firbin clots that are denser and resistant to fibrinolysis) 4. Increased platelet activity
58
What does PT stand for?
Prothrombin time
59
What does PTT stand for?
Activated Partial thromboplastin time
60
What is thought to contribute to aspirin resistance in dogs?
70% normal dogs have defect in G-protein signaling
61
What factor is increased in Cushing's that may be a risk for hypercoag?
Factor 8
62
How does decreased HCT affect TEG?
Hypercoag
63
How does plt
Hypocoag
64
What affects R in TEG?
Coag factors | NOTE: Heparin prolongs it
65
What affects K and alpha in TEG?
Fibrinogen Factor 13 Platelets
66
What affects MA in TEG?
Fibrin production | Platelet function
67
What dz have been noted on TEG to result in hypercoag?
``` Parvo virus Cancer DIC PLE PLN ``` ****NOTE: HAC same as controls****
68
What dz have been noted on TEG to result in hypocoag?
Cancer DIC (clinical bleeding) HCM (some cats)
69
What are risk factors for DIC?
``` Prolonged hypotension SIRS Changes in blood flow Tissue damage change in vascular integrity Hemolysis ```
70
What is mediator of DIC?
Release of TF!!!! From monocytes and endothelial cells | Which activates Factor 7 (extrinsic pathway) = LOTS of thrombin which cleaves fibrinogen to make fibrin
71
What are the components of a diagnosis of DIC?
1. Condition that predisposes to DIC 2. Prolonged coags 3. Low Platelets 4. Increased d-dimers and FDPs 5. Decreased AT 6. Evidence of thrombi
72
What is seen on a coag that would EXCLUDE DIC?
Normal D-dimers
73
Should heparin be used for DIC?
Controversial Thought to prevent further thrombi BUT no studies in humans that there is a benefit DOES NOT work if there is NO AT!!!
74
What syndrome is noted in Greyhound with arthritis?
Felty's syndrome (rheumatoid arthritis)
75
What are the two main forms of erosive polyarthritis?
1. Rheumatoid Arthritis | 2. Periosteal Proliferative Polyarthritis (CATS)
76
Which breed of young dogs gets polyarthritis that does not respond well to treatment?
Adolescent Akitas
77
What are the vaccines that dogs and cats develop polyarthritis with?
Cat: Calicivirus Dogs: Distemper
78
What are the 4 types of IMPA?
1. Primary IMPA 2. Reactive to infection/inflammation remote from joint 3. Enteropathic (GI or hepatic disease) 4. Neoplasia
79
For Type 4 IMPA in cats, what should be considered?
Myeloproliferative disease
80
What should normal joint fluid look like?
81
What does IMPA joint fluid look like?
82
Do repeat joint taps every 3 weeks result in neutrophilic inflammation in the joints?
NO!!
83
What is the transit time of neutrophils?
About 10 hours
84
What is the transit time of lymphocytes?
30 mins | BUT recirculate for years
85
What is the transit time of monocytes?
12 hours
86
What is the transit time of eosinophils?
30 mins
87
What is the transit time of basophils?
30 mins
88
What is found on an iron panel?
Serum iron (iron bound to transferrin) TIBC (serum transferrin concentration % saturation = % transferrin bound by iron (normal about 30%) Ferritin = Storage iron in serum = Reflects total body iron
89
What does hepcidin do?
Binds to cell surface and internalizes ferroportin (only iron exporter) = NO export of iron (also inhibits DMT1 expression) Increased with inflammation Decreased with anemia, hypoxia
90
What would you see in the BM of a nonregenerative IMHA?
Erythroid hyperplasia = Expansion of immature erythyroid precursors
91
What are T cell markers?
CS 3, CD4, CD5, CD8
92
What are B cell markers?
CD21, CD22
93
What does CD34 mark?
Immature lymphoid/myeloid precursors
94
What are the difference on PARR Of B and T cells?
B cells = V, D, J genes | T cells = V, J genes
95
What type of lymphocytosis can be seen with Chronic E. canis?
Lymphocytosis Granular Lymphocytes = Homogenous CD8 Tcells
96
Does involvement of the bone marrow change prognosis of leukemia?
NO!
97
What is important for B cell leukemias?
Cell size important Small = BAD (MST 15 DAYS!!) Large = Better (MST 17 months)
98
What is important for T cell leukemias?
is important >30K Poor prognosis 1K days!
99
What type of lymphocytosis occurs with Addison's disease?
Increased in CD4 T cells, CD8 T cells, and B cells = HETEROGENOUS