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ACVIM General - Imp stuff > Immunology/Blood > Flashcards

Immunology/Blood Flashcards

1
Q

What is the lifespan of a monocyte

A

3 days

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2
Q

What enzymes do mast cells and basophils secrete

A

-histamine
-bradykinin
-serotonin
-eosinophilic chemotactic factor
-heparin

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3
Q

Which cells secrete interferon Y (gamma)?

A

NK cells

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4
Q

Which types of cells do NK cells kill

A

Anything that does not possess an MHC I molecule on the surface

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5
Q

What is the lifespan of neutrophils?

A

12-24 hours

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6
Q

Where are the proteins of the complement system synthesized?

A

Liver

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7
Q

What is the most abundant protein inn the alternate pathway of activation?

A

C3

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8
Q

What breed is predisposed to C3 deficiency immunodeficiency?

A

Brittany spaniels

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9
Q

In intravenous IgG therapy, what is the MOA?

A

Works by binding to the Fc receptor of the immunoglobulin so the antigen cannot bind

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10
Q

What is the first immunoglobulin to be secreted?

A

IgM

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11
Q

What is the largest Ig?

A

IgM

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12
Q

What is the most common immunoglobulin in IMHA?

A

IgG

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13
Q

What is the immunoglobulin seen in intravascular IMHA?

A

IgM

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14
Q

What is the 1/2 life of IgM?

A

24 hours

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15
Q

What is the only antibody that can act intracellularly?

A

IgA

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16
Q

What Ig coats all mucosal surfaces?

A

IgA

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17
Q

What is the 1/2 life of IgE?

A

2-3. days

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18
Q

What is the 1/2 life of IgG?

A

3 weeks

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19
Q

What Ig constitutes 75% of the antibodies in the blood?

A

IgG

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20
Q

What Ig is involved in allergic rxn?

A

IgE

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21
Q

Which MHC class presents endogenous antigen to cytotoxic T-cells and NK cells?

A

Class I MHC

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22
Q

Which MHC class presents exogenous antigen to T-helper cells?

A

Class II MHC

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23
Q

Name the TLR associated with the following:
-Lipoprotein
-Gram positive bacteria
-Double stranded RNA
-LPS from gram negative bacteria
-Flagellan
-Single strand RNA of viruses
-Double stranded DNA of bacteria and herpes virus
-Gram negative bacteria

A

-Lipoprotein: TLR1
-Gram positive bacteria: TLR2, NOD1
-Double stranded RNA: TLR3
-LPS from gram negative bacteria: TLR4
-Flagellan: TLR5
-Single strand RNA of viruses: TLR7
-Double stranded DNA of bacteria and herpes virus: TLR9
-Gram negative bacteria: NOD2

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24
Q

What are the types of APCs?

A

Dendritic cells
Activated macrophages
Activated B cells
Activated T helper cells

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25
Q

What is the receptor for T-helper cells?

A

CD4+ receptor - clip onto MHC II molecules

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26
Q

What is the cytotoxic T-cell profile (TH-1)?

A

IL-2, IL-12

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27
Q

What is the B-cell profile (TH-2)?

A

IL-4, IL-6

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28
Q

What is the receptor for cytotoxic killer T cells?

A

CD8+ receptor - clips onto MHC I molecules

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29
Q

What is the target for metronomic chemo?

A

Regulatory T-cells.

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30
Q

What is the MOA of the Lyme vaccine?

A

All available canine Lyme disease vaccines produce borreliacidal antibodies in the dog in response to vaccinal outer surface protein A (OspA). These antibodies work in the tick’s gut to bind the bacteria during the blood meal, sterilizing the gut of the tick and preventing transmission of bacteria into the dog.

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31
Q

What are the fever profile cytokines?

A

IL-1, IL-6, TNF-a

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32
Q

What are some examples of acute phase proteins?

A

IL-1, IL-6, TNF-a, C-reactive protein, Amyloid-A in cats, haptoglobin

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33
Q

What are some examples of negative acute phase proteins?

A

Albumin, transferrin, a-lipoprotein

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34
Q

What is the CLAD immunodeficiency and what breed is predisposed?

A

Defective intern CD11b/CD18 prevents PMN migration out of bloodstream
Irish setter

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35
Q

What breed is predisposed to IgA deficiencies?

A

GSD

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36
Q

What cytokine is a eosinophil attractant? Where is it produced?

A

IL-5
Produced in TH2 cells and mast cells

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37
Q

What is the function of IL-1? Where is I produced?

A

Produced in any cell
Function: pro-inflammatory, +. APP, fever, increased IL-6, fibroblast proliferation

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38
Q

What is the function of IL-2? Where is it produced?

A

Produced by activated T-cell
Function: T-cell proliferation, NK cell

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39
Q

What is the function of. IL-4? Where is it produced?

A

Produced in TH2 cells
Function: AB class switch to IgE

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40
Q

What is the function of IL-6? Where is it produced?

A

Produced in RES
Function: fever + APP

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41
Q

Function of IL-10? Where is it produced?

A

Produced in TH2 cells
Anti-inflammatory

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42
Q

Function of IL-12? Where is it produced?

A

Produced in TH1 cells, macrophages
Function: stimulate NK cells + cytotoxic T-cells

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43
Q

Function of IFN-gamma? Where is it produced?

A

Produced in NK cells, TH1 cells
Function: B-cell class switch to IgG

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44
Q

Which cytokine is associated with fever and cachexia of chronic disease? Where is it produced?

A

TNA-alpha
Produced in macrophages and T-cells
Function: fever, mediates acute inflammation

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45
Q

What cytokine is associated with immunosuppression and B-cell class switch to IgA?

A

TGF-beta
Produced in platelets and nucleated cells

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46
Q

Where do the following T-cell receptors bind to?
-CD28
-CD3
-CD4
-CD8

A

-CD28: APC during T-cell activation
-CD3: T-cell intracellular bound to T-cell receptor
-CD4: TH2 helper t-cell
-CD8: TH1 cytotoxic t-cell

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47
Q

What are the B-cell receptors?

A

CD21, CD79, CD45

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48
Q

How do attenuated vaccines stimulate the immune system?

A

Stimulation of cytotoxic T-cells

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49
Q

How do carrier vaccines stimulate the immune system?

A

Stimulate memory cytotoxic T-cells

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50
Q

How do DNA vaccines stimulate the immune system?

A

Stimulate memory cytotoxic t-cells

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51
Q

How do non-infectious vaccines stimulate the immune system? What is an example of this vaccine

A

Rabies vax
Stimulates T-helper and B-cells but not cytotoxic T-cells

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52
Q

How do adjuvants vaccine work?

A

Slow release of. Ag – lead to granuloma formation

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53
Q

What are the shock organs of dogs? Cats?

A

Dogs - liver and GIT
Cat - lungs and GIT

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54
Q

What type of hypersensitivity is associated with atopic individuals? What Ig is involved?

A

Type I hypersensitivity
IgE primes mast cells and is a chemoattractant for eosinophils
Atopic individuals are TH2 polarized

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55
Q

What is the effect of alpha agonists on the regulation of mast cell degranulation?

A

Positive effect – ex: norepinephrine, phenylephrine

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56
Q

What is the effect of beta agonists on the regulation of mast cell degranulation?

A

Negative effect – mast cell “stabilizer” – ex: epinephrine

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57
Q

What is a type II hypersensitivity?

A

-Red blood cell antigen: incompatible blood transfusion, hemolytic disease of newborns (neonatal isorythrolysis)
-Rxn to drugs –> destruction to RBC (2ry IMHA)
-Can be associated with infectious diseases

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58
Q

What type of hypersensitivity is associated with immune complex diseases (Arthus reaction)? What are some examples?

A

Type III hypersensitivity
Immune complex formation (antigen and IgG) and lodging in the small vessels (glomerulus, synovial, choroid plexus) –> innocent bystander effect
Ex: polyarteritis, polyarthritis, vasculitis, SLE, glomerulonephritis, uveitis

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59
Q

What is a type IV hypersensitivity rxn?

A

Delayed reaction involving memory T-cells
Ex: tuberculin rxn - inflammation 24-72H

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60
Q

What is the defect in SCID (severe combined immunodeficiencies)? What breeds are associated?

A

Autosomal recessive loss of T and B-cells
Horses, Jack russels

X-linked in bassets and Welsh corgis

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61
Q

What breed is predisposed to lethal acrodermatitis? What is the deficiency>

A

T-cell deficiency
Bull terriers

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62
Q

What breed is predisposed to pneumocystis carina pneumonia?

A

Dauschunds

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63
Q

How does FeLV/FIV lead to immunodeficiency?

A

CD4+ Th-cell deficiency and lymphopenia w relative normal B-cells

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64
Q

What breed is predisposed to cyclic neutropenia?

A

Grey coated collies

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65
Q

What is the action of NK-kB?

A

Increase expression of anti-apoptotic genes

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66
Q

What breeds are predisposed to pyruvate kinase deficiency? What is the sequelae?

A

Abyssinian, somali cafés
Beagles, cairn terriers, Westies, basenjis

Results in hemolytic anemia that will be neg Coombs or agglutination
Dogs: leads to progressive myelofirbosis and osteosclerosis of bone marrow –> liver cirrhosis
Generally life limiting

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67
Q

What breeds are predisposed to PFK deficiency? What is the mode of inheritance? What is the sequelae?

A

English springer spaniels, American cocker spaniels
Autosomal recessive
Prevents metabolism of glucose into available energy –> exercise intolerance and muscle disease
Dogs have sporadic episodes of hyperventilation-induced intravascular hemolysis and hemoglobinuria
Gx: supportive care and avoid triggers

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68
Q

What breed is predisposed to vWFD type 1? type 2? type 3?

A

Type 1- doberman
Type 2- German shorthaired, wire-haired pointer
Type 3- Scotties, shelties

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69
Q

How do you diagnose vWFD?

A

Type 1 and 3 (quantitative) – plasma vWF antigen concentration
Type 2 - platelet function analyzerH

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70
Q

How can you treat vWFD?

A

Can use desmopressin acetate – works better in humans, but can help control bleeding in some hemostatic disorders. Give 30min before sx when using prophilactically
Blood products - fresh whole blood, FFP, cryoprecipitate (best - contains the most concentrated vWF, less volument)
vWF has a short 1/2 life (12h)

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71
Q

What is the MOA of plavix?

A

P2Y12 receptor antagonist (ADP receptor antagonist)

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72
Q

What is hemophilia A?

A

Deficient factor VIII
x-linked recessive, primarily affects males

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73
Q

What is hemophilia B?

A

Deficient factor IX
x-linked recessive, primarily affects males

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74
Q

How do you diagnose hemophilia A? B?

A

Both will have prolonged PTT or ACT with normal PT
Definitive diagnosis via measurement of coagulation factor activity

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75
Q

What is hemophilia C?

A

Factor XI deficiency
Kerry blue terriers, springer spaniels, great pyrenees, Weimaraner, cats

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76
Q

What is hageman trait?

A

Feline factor XII deficiency
Most common defect of intrinsic pathway
Autosomal recessive
Does not typically cause hemorrhage
Prolonged PTT and ACT
Can have concurrent hemophilia A or B

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77
Q

What is the lifespan of a RBC in dog? Cat?

A

Dog - 100 d
Cats - 70d

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78
Q

What spherocyte count per HPF is diagnostic for IMHA? Suspicious?

A

Diagnostic: >=5/HPF
Suspicious: >=3/HPF

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79
Q

What integrin does the OSP of Borrelia share similarities?

A

Integrin CD11a/18

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80
Q

What cancer is associated with myasthenia gravis?

A

Thymoma

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81
Q

What cancer is associated with ITP?

A

Multiple myeloma

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82
Q

Degenerative myelopathy is linked to which MHC molecules?

A

DLAs - A3, A7, A10

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83
Q

Antinuclear antibodies causing immune diseases are linked to what?

A

DLA-12

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84
Q

SLE is associated with what MHC molecule?

A

DLA-A7

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85
Q

Myasthenia gravis in Newfies is linked to what?

A

MHC1

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86
Q

What antibiotic has an association of causing an immune mediated disease in Dobermans? What immune mediated disease?

A

Sulfas
IMPA

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87
Q

What antibiotic is associated with immune mediated diseases?

A

Penicillin/cephalosporins

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88
Q

What medications might have an association with immune mediated disease?

A

Abx- sulfa, penicillin/cephalosporin
Methimazole
Phenobarbital
Fenbendazole
Griselfulvin
Promeris
NSAIDs
Vaccine (association not proven)

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89
Q

How do penicillins/cephalosporin cause immune mediated diseases?

A

They adhere to cell membrane - making it easier for the immune system to recognize.

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90
Q

What types of cancers have been associated with immune mediated diseases?

A

Lymphoma
Leukemia (including FeLV)
Hemophagocytic syndrome of histiocytic sarcoma
Bronchoalveolar carcinoma
Soft tissue sarcoma
Thymoma
MM

91
Q

What are signs of immune mediated destruction per the consensus guidelines needed to make a diagnosis of IMHA? And how many do they need for a diagnosis

A

Need 2 or more to and 1 or more to sign of hemolysis
Spherocytes (dog only)
Positive slide agglutination test or positive that persists with washing
Positive direct antibody test (Coombs) or flow cytometry

92
Q

What are signs of hemolysis per the consensus of IMHA? How many are needed to make a diagnosis

A

1 or more to hemolysis signs and 2 or more signs of immune mediated destruction
- hyperbilirubinemia: icterus, elevated Tbili, bilirubinuria (any in cats, 2 or more in dogs)
- hemoglobinemia/hemoglobinuria
- spherocytosis/erythrocyte ghosts

93
Q

What is waldenstrom macroglobulinemia?

A

Uncommon cancer that comes from malignant B-cells (IgM) – causes hyperviscosity

94
Q

What cytokines are responsible for causing cachexia in cancer?

A

IL-1, IL-6, TNGa, TGFb, NF-kb

95
Q

Which cytokines are associated with the mechanism of hypercalcemia of malignancy>

A

PTH-rp
IL-1
IL-6
PGE 1 and 2
TGFa+b
RANKL
Osteolysis
Calcitriol

96
Q

What can hyperglobulinemia lead to in a cancer setting?

A

Bence jones protein can cause light chain renal tubular casts –> interstitial nephritis

97
Q

What are negative prognostic indicators that you can find on a CBC with lymphoma?

A

Anemia, neutrophilia

98
Q

What types of cancers are associated with a severe (>70K) neutrophilic? What is the mechanism?

A

Dog - Lung CA, renal tumors, GI LSA, FSA, rectal polyps
Cats - Lung SCC, dermal tubular ACA
Mechanism: increase G-CSF or GM-CSF

99
Q

What types of cancer are associated with an eosinophilia? Mechanism?

A

Primarily MCT (esp cats) and lymphoma
Mechanism: increased IL-5

Also in dogs (oral fibrosarcoma, mammary gland tumor, leiomyosarcoma), cats (oral SCC, bladder TCC)

100
Q

What types of cancers are associated with immune mediated thrombocytopenia?

A

Lymphoma, MM, hemangiosarcoma - more common
Also MGT, MCT, nasal ACA, FSA, histiocytic

101
Q

What is the mechanism of hypercoagulability in MCT?

A

Increase heparin –> cofactor for AT III –> inactivation of factors XII, XI, X, IX

102
Q

What is Dermatofibrosis? Who is predisposed and why?

A

Gene defect (BHD gene on chromosome 5) in GSD leads to slow growing cutaneous nodules –> bilateral renal cystadenocarcinomas or cystadenomas
- Females will also have uterine leiomyomas
Autosomal dominant

103
Q

What is superficial necrolytic dermatitis? What’s the mechanism of why it happens?

A

Hepatocutaneous syndrome - associated with liver disease
- mucocutaneous junctions
Glucagon secreting tumors of liver and pancreas
Gluconeogenesis –> AA catabolism –> hypoaminoacidemia –> epidermal protein depletion

104
Q

What cancers are associated with paraneoplastic alopecia?

A

Pancreatic and biliary carcinoma
Most have metastatic disease
Foot pad involvement common

105
Q

What cancer is associative exfoliative dermatitis associated with?

A

Thymoma
Starts as nonpruritic scaling, mild erythema of head –> neck, trunk, limbs –> scaling gets worse –> alopecia
Mechanisms unknown
Resolved with sx

106
Q

What cancers are associated with myasthenia grave?

A

Dog: thymoma, OSA, cholangiocellular CA, oral Sarcoma, nonepitheliotropic cutaneous LSA
Cats: thymoma

107
Q

What cancers is hypertrophic osteopathy associated with? What other non-cancer diseases is it associated with?

A

Most common with lung tumors
* Also metastatic OSA
* Non-lung: renal, bladder
rhabdomyosarcoma, HCC, esophageal
ACA, prostatic CA, schwannoma
* Cats: adrenal, renal

Also heartworm, bacterial endocarditis, PDA, Spirocera lupi esophageal granulomas, esophagel FB

108
Q

What cytokines are associated with fever?

A

IL-1, IL-6, TNF-a –> prostaglandin E2 –> hypothalamus

109
Q

What cancers is paraneoplastic pemphigus associated with? What breeds are overrrepresented?

A

Dog: thymoma, thymic lymphoma, splenic sarcoma
Cat: lymphocytic thymoma
MBD, GSD, Collie, Spaniel, Weiner dog, Lab, Poodle, Scottie

110
Q

What is CD molecule used in flow cytometry?

A

CD-21 - complement receptor on B-cell and rare T-cell

111
Q

What is the CD molecule used in IHC?

A

CD79a – major part of B-cell receptor

112
Q

What CD molecule is in almost all B-cells?

113
Q

What CD molecule is a major part of T-cells?

114
Q

What is the CD molecule for T-celper cells?

115
Q

What CD molecule is not found in dog B-cells, but is integral for T-cell antigen response and a reliable indicator of T-cell only?

116
Q

What is the CD molecule in cytotoxic T-cells?

117
Q

What CD molecule is found in acute leukemia?

A

CD34 - endothelial cell ligand for integrins
Present on lymphoid or myeloid cells
Absence does not rule out leukemia

118
Q

What CD molecules do thymomas commonly express?

A

CD4 and CD8
> or = 10% of lymphocytes

119
Q

What infectious disease has high evidence of being associated with immune mediated hemolytic anemia in dogs?Cats?

A

Dog - Babesia Gibson in fighting breeds, FL
Cat - Mycoplasma haemofelis

120
Q

In which diseases processes can we see Coombs positive anemia that is not IMHA?

A

Leishmania, HW, Bartonella, FeLV

121
Q

What’s the specificity of saline auto agglutination test for IMHA?

A

Remember use room temp saline
Remember not to be performed post-transfusion
1:1 blood to saline - 95% specific (rules it in)
1:4 blood to saline 100% specific

122
Q

What immunotherapy can be used for tx of Bowen’s disease, SCC of pinna or superficial MCTs?

A

Imiquimod - active, non-specific topical immunotherapy. It’s a macrophages immunostimulant that induces an inflammatory response with lesion resolution.

Bowen’s disease (viral transformation of epithelial cells)

123
Q

What’s the sensitivity and specificity of direct Coombs test for IMHA?

A

Sensitivity - 61-82% dogs, 82% cats
Specificity 94-100%
Cannot be performed if agglutination persists after washing

124
Q

What is the ANA test for IMHA?

A

Anti-NUCLEAR antibody - tests for serum antibodies against nuclear material
IFA antibody test results
Sensitive, but not specific (false positive up to 20%)

125
Q

What type of hypersensitivity do we see with SLE? What are some manifestations with SLE?

A

Type III hypersensitivity - multi-systemic
FEVER IN 100%
Other manifestations:
1. Polyarthritis
2. Glomerulonephritis
3. Dermatologic involvement - erythema, ulcers, crusts
4. Lymphadenosplenomegaly
5. Hematologic - leukopenia, anemia, thrombocytopenia
Rare: myositis, pleuropericarditis, CNS, PNS

126
Q

How do we diagnose SLE?

A

> 2 or = separate manifestations of autoimmunity + positive ANA-titers

OR

> 3 or = separate manifestations of autoimmunity even in the absence of detectable ANA

127
Q

What breeds do we see T-zone lymphoma in? What sequelae do we see?

A

Goldens and Shih Tzus

Immunosuppressive T-cell: Subtype of T-cell lymphoma characterized by unique histologic pattern and cytomorphology, immunophenotypic loss of CD45 expression, and an indolent clinical behavior

Get adult onset papilloma virus, adult onset demodecosis

128
Q

What is flow cytometry? How can it be used in immune mediated diseases?

A

Used to evaluate cell suspension. Need living cell sample.

S-phase distribution in the cell

Can measure anti-neutrophils or anti-platelet antibodies
Specific, but not sensitive (negative does not rule it out)

129
Q

What’s the prognosis of amegakaryocytic IMT?

A

Poor - 86% mortality rate
Cannot make their own platelets

130
Q

What would we expect to see in a normal joint fluid cytology? What % of monos? What % of PMNs?

A

Clear, colorless, viscous
0-3 cells/HPF
90100% monos
0-10% PMNs

131
Q

What Ig is associated with rheumatoid immune mediated polyarthritis?

A

Rheumatoid factor - positive for anti-IgG antibodiesW

132
Q

What are the types of IMPA?

A

Erosive: rheumatoid or periostea proliferative polyarhtitis (male neutered cats predisposed)

Non-erosive: Share pei fever, drug induced, idiopathic

133
Q

What is the IL associated with Shar-Pei Fever? What is the mode of inheritance?

A

Autosomal recessive - increased IL-6 and amyloid deposits

134
Q

What drug is associated with IMPA? What breed do we see it in?

A

Sulfa antibiotics
Dobermans

135
Q

What are the types of idiopathic IMPA?

A

Type I- uncomplicated, most common
Type II- infections remove from joints
Type III- complicated by GIT disease
Type IV- neoplasia remove from joints

136
Q

What would we see in the skin biopsy of a dog with pemphigus vulgaris?

A

IM attack against DESMOSOMES
Separation of the skin cells in the supra basal region of the lower epidermis (ie ACANTHOLYSIS)
Mucocutaneous junction only - severe deep, denuded

137
Q

What would we see in the skin biopsy of a dog with pemphigus folleaceous?

A

Most common IM skin disease in SA
Attacks desmosomes –> severe crusting of haired and non-haired skin
Biopsy shows acantholysis and lesions just above the dermis

138
Q

What drug can induce pemphigus folleaceous?

A

Thiol - binds to cell surface (antibiotics, promeris)

139
Q

What breeds are predisposed to developing discoid lupus?

A

Collies, Shelties, GSD, huskies

140
Q

What CS do we see with discoid lupus?

A

Lesions confined to the nasal planum – loss of cobblestone, depigmentation

141
Q

What is superficial necrolytic dermatitis?

A

AKA hepatocutaneous syndrome
Metabolic disease, not immune disease

142
Q

What is the MOA of glucocorticoids?

A

Stabilizes endothelial cells inhibiting local chemotaxis and decreased leukocyte migration
Inhibits release of arachidonic acid –> less leukotrienes, thromboxane, prostaglandins
Redistributes monocytes and T-lymphocytes from blood to lymphatics
Decreases macrophage function by down regulating Fc receptor expression, decreased antigen processing/presentation
Suppresses T-cell function, decreased cytokines, induced apoptosis of T-cells
B-cell effect is minimal though with chronic use AB production may be diminished

143
Q

Describe the arachidonic acid casdade

A

Membrane phospholipids –> arachidonic acid
- Leukotrines (via 5-LOX) –> allergy, inflammation (B4 signals PMNs), gastric damage
- PGG2 (via COX-1 and 2) –> PGH2
*Prostaglandins (gastroprotective)
*Prostacyclins (inflammation, pain)
*Thromboxanes (inflammation, pain)

144
Q

How much of budesonide reaches systemic circulation?

A

10%
90% first pass metabolism

145
Q

What is the MOA of azathioprine?

A

Purine analog –> faulty DNA synthesis (S-phase)
Affects B-cells > T-cells

146
Q

What are SE of azathioprine?

A

Hepatotoxicity
Myelotoxicity (limits use in cats)
Pancreatitis

147
Q

What is the MOA of mycophenolate? SE?

A

Inhibits purine synthesis. Decresed B and T cell production

SE: GI, HGE, lymphopenia

148
Q

MOA leflunomie
SE

A

MOA: inhibits pyrimidine synthesis. decreased both T and B cells
SE: GI (anorexia, V, melena), myelotoxin, hypotrichosis/alopecia
Pharmacokinetic drug monitoring

149
Q

What is the MOA of cyclosporine?

A

Calcineurin inhibitor - inhibits T-cell activation and decreases IL-2 secretion

SE: GI, gingival hyperplasia, papillomatosism, hyperkeratosis, hirsutissm

150
Q

What is the MOA of tacrolimus?

A

Calcineurin inhibitor - inhibits T-cell activation and IL-2 (like cyclosporine). Also inhibits B-cells

SE prevent PO use - anorexia, vasculitis, intussusception
Used topically

151
Q

What is the MOA of sirolimus (rapamycin)? SE?

A

Similar effect to tacrolimus
MOA: macrocyclic abx that blocks gene transcription so that cells are stuck in G1
T and B cells
SE: nephrotoxic, HUS, hypertension, hyperlipidemia

152
Q

What is the MOA of imiquamod? Use?

A

Binds to and activates TLR-7 –> stimulating local innate immunity
Topical for carcinoma in situ, cutaneous LSA

153
Q

What is the MOA of chlorambucil?

A

Alkylating agent - cytotoxic against B-cells
SE: minimal myelosupppression, GI (nausea, V, A)

154
Q

What is the MOA of cyclophosphamide? SE?

A

MOA: alkylates DNA during S-phase
Decreases both B and T cells
SE: myelotoxic, Gi, alopecia, sterile hemorrhagic cystitis
ACVIM consensus - DONT use in IMHA

155
Q

What is the MOA of methotrexate? SE?

A

Inhibits folic acid synthesis results in decreased DNA synthesis in S-phase
SE: myelotoxic, GI

156
Q

What is the MOA of cytosine arabinoside”

A

Pyrimidine analog inhibits DNA polymerization
Used in GME

157
Q

MOA 5-fluoroUracil

A

Pyrimidine analog inhibits DNA polymerization

158
Q

What is the consensus on thromboprophylaxis in IMHA dogs?

A

All dogs w/ PLT >30K
Start at diagnosis -highest risk first 14D
D/C when in remission and no longer on red

Thrombi form under low-shear (fibrin) with much smaller role of PLT

Use ungractionated heparin or LMW heparin

Antiplatelet drugs if heparins not feasible - aspirin, plavix

159
Q

What is the use and MOA of romiplostim?

A

Novel approach for IMT
MOA: thrombopoietin receptor (TPO) agonist

160
Q

What are negative prognostic indicators. for IHA

A

pre-existing systemic infections
hemophagocytic syndrome
thromboembolic complications

161
Q

Where is vWF stored?

A

Weibel Palade Bodies - storage granules on endothelial cells

162
Q

What cells produce vWF?

A

Endothelial cells

163
Q

Where is vWF secreted?

A

Into sub endothelial matrix and plasma

164
Q

What agonists release vWF?

A

Thrombin, histamine

165
Q

What’s the main receptor involved in vWF?

166
Q

What receptors on the PLT surface are activated once vWF adhered?

A

GPIIb/IIIa, GPIa/IIa - binds firmly to collagen

167
Q

What’s glanxmanns thrombasthenia?

A

Genetic defect in GPIIb/IIIa

168
Q

vWF is needed for aggregation of PLT at (low/high) shear rates

A

HIGH (arterioles)

169
Q

What is vWF type1? What breeds are predisposed?

A

Low plasma vWF level
All multimers present
Mild to mod bleeding tendency
Breeds: Doberman, Poodle

170
Q

What is vWF type 2? What breeds are predisposed?

A

Variable plasma vWF level
Large multimers absent
Mod to severe bleeding tendency
Breeds: GSP, GWP

171
Q

What is vWF type 3? What breeds are predisposed?

A

Absent plasma vWF level
All multimers absent
Severe bleeding tendency
Breeds: Scotties, shelties

172
Q

How do we diagnose type I vWF?

A

ELISA - measures amount of vWF:Ag in plasma compared to standard of 100
-70-180% normal
-50-69% borderline
-0-49% low

173
Q

How do we diagnose type II vWF?

A

Qualitative assay - ELISA measures binding of canine vWF to collagen (dependent on high molecular weight multimers)

174
Q

How do we diagnose type III vWF?

A

ELISA - measures amount of vWF:Ag in plasma compared to standard of 100
-70-180% normal
-50-69% borderline
-0-49% low

175
Q

How do we prophylactically tx vWF deficiency?

A

Desmopressin (DDAVP)
MOA: enhanced release of vWF from storage
Administer 30min before tx
Only to be used in vWF type I + II
Can only administer SID given risk of water retention and hyponatremia

176
Q

What blood therapy can we give vWF deficient dogs?

A
  • Cryoprecipitate: #1 choice as has the most vWF concentrate in low volume. Short 1/2 life (8-12H) - needs to be redosed
  • FWB
  • FFP
177
Q

What do alpha granules contain?

A

-vWF
-Coagulation factors (fibrinogen, FV, FXIII)
-Adhesion molecules (P-selectin)

178
Q

What is the ligand that P-selectin binds to on endothelial cells and leukocytes?

179
Q

What do dense granules contain?

A

-ADP - PLT agonist
-Serotonin - PLT agonist
-Calcium - needed for 2ry hemostasis + PLT activation
-Short-chain polyphosphate - procoagulant + antifibrinolytic

180
Q

What’s the MOA of aspirin and NSAIDs?

A

Inhibit cyclooxygenese
-Aspirin: irreversibly
-NSAIDs: reversibly

Cyclooxygenase is needed for thromboxane A2 production (PLT agonist)

181
Q

What’s the binding site for coagulation factors?

A

Phosphatidylserine (PS)

182
Q

What breed is predisposed to a defect in PS (Scotts syndrome)>

A

GSD
Also defect in microvesiculation

183
Q

What’s Basset Hound Thrombopathis

A

Defective CalDAG-GEF1

184
Q

What’s the MOA of plavix

A

P2Y12 receptor antagonist (receptor for ADP)

185
Q

Name inhibitors of 1ry hemostasis

A

NO and prostacyclin (prostaglandin E12)
High concentrations of FDPs
Inhibit PLT activation

186
Q

What factors are involved in the extrinsic pathway?

A

Tissue factor
Factor VII
Calcium
Occurs in fibroblasts

187
Q

What factors are involved in the intrinsic pathway?

A

ENzyme cong factors- FXII, FXI, FIX
Cofactor- FVIII
Ca
Phosphatidylserine (PS)
OCCURS IN PLT SURFACE

188
Q

What factors are associated w common pathway?

A

Enzyme coag- FX, prothrombin (FII), FXII (crosslinker)
Cofactor- FV
Substrate: fibrinogen
Ca
PS
Product: fibrin

189
Q

Is FXII of the intrinsic pathway involved in initiating hemostasis?

A

NO – deficient animals (Hageman trait - cats) have no clinical bleeding
Involved in fibrinolysis

190
Q

What is the cell based model?

A

takes into account all 3 processes (primary hemostasis, secondary hemostasis, fibrinolysis)
Divided into initiation, amplification, propagation

191
Q

What happens in the initiation phase

A

Extrinsic pathway on the surface of fibroblast
Mediated by TF
TF binds to FVII (activates it)–>TF-FVII complex activates FX-> FXa activates FV—> FXa-FVa-PS-Ca2+ (generates thrombin)

192
Q

What is the MOA of rivaroxaban?

A

FXa inhibitor

193
Q

What is the amplification phase

A

Accomplished via thrombin activating intrinsic pathway factors
Now happening in the PLT surface
Thrombin amplifies its own production –> fibrin formation

194
Q

What is hemophilia A? How do we diagnose it?

A

Lack of factor VIII - presents formation of intrinsic tenase complex
X-linked recessive (primarily affects males)
Dx: prolonged PTT or ACT with normal PT
Definitive dx - measure coat factor activity (normal= 50-150%)

195
Q

What is hemophilia B? How do we diagnose it? How do we diagnose it?

A

Lack of factor IX - presents formation of intrinsic tenase complex
X-linked recessive
Dx: prolonged PTT or ACT with normal PT
Definitive dx - measure coat factor activity (normal= 50-150%)

196
Q

What are the vitamin K dependent factors?

A

Factor 2,7,9,10

197
Q

What are the vitamin K dependent inhibitors?

A

Protein C and Protein S

198
Q

What is the action of warfarin?

A

Inhibits vitamin K epoxide reductase - needed for recycling vitK to its active form
Causes vitK deficiency (factors II,VII, IX, X)

199
Q

Where is antithrombin produced?

A

Liver, duh

200
Q

What is the action of antithrombin? What molecule enhances its activity?

A

Inhibits activity of most coagulation factors
Greatest effect on thrombin (IIa)
Heparin enhances activity

201
Q

Where is protein C produced?

A

Liver, duh

202
Q

What enzyme enhances the activity of Protein C?

203
Q

What is the action of bradykinin in coagulatioN?

A

Potent inducer of tissue plasminogen activator + stimulation of release of NO and prostacyclin (PLT. inhibitors)

204
Q

What AA is involved in the plasmin production?

A

Plasminogen binds to fibrin through lysine residues - lysine is cleaved from the fibrin –> weak plasminogen binding to fibrin

205
Q

What is the job of aminocaproid acid?

A

Competitive inhibitor of plasminogen (acts like lysine)

206
Q

What can we detect w a BMBT?

A

Deficiencies in PLT #, deficient vWF, abnormalities in vascular integrity, abnormalities in PLT function

207
Q

What can affect the result of the vWF:Ag concentration by ELISA test?

A

Sample hemolysis: falsely decrease
Severe inflammation, pregnancy: falsely increased

208
Q

What is the prothrombin time (PT) evaluating?

A

Extrinsic (FVII, TF)
Common (FX, FV, prothrombin, fibrinogen)

209
Q

What is the activated partial thromboplastin time (aPTT) evaluating?

A

Intrinsic (FVIII, FIX, FXII)
Common (FX, FV, prothrombin, fibrinogen)

210
Q

What is the activated clotting time (ACT) evaluating?

A

Whole blood
Visual clot formation
Severe thrombocytopenia can affect results

211
Q

What are fibrinogen degradation products (FDPs) measuring?

A

FDPs created when plasmin lysis plasminogen
Presence of FDPs indicated plasmin activity (fibrin clot breakdown)
Happens in DIC, anticoagulant rodenticide, hepatic dz, thrombosis, IMHA, neoplasia, pancreatitis, GDV, heatstroke

212
Q

What is D-dimer measuring?

A

Form of FDP that can only be generated from breakdown of cross linked fibrin
Short 1/2. life - presence indicated recent (5h) fibrinolysis

213
Q

When is a TEG considered hyper coagulable?

A
  • Shorter R-time (faster time to start clot formation)
    -Steeper alpha-angle (more rapid clot formation)
    -Greater maximum amplitudeW
214
Q

When is a TEG considered hypocoagulable>

A

-Prolonged R time (decrease in coag factors)
-Significantly decreased alpha-angle and MA (w/normal R time) - if thrombocytopenic
-Narrow alpha angel and MA - coagulopathic patients w low fibrinogen (DIC)

215
Q

What artifacts can affect TEG?

A

Anemia - causes hyper coagulable tracing
Erythrocytosiis - causes hypo coagulable tracing

216
Q

What is the MOA of heparin?

A

potentiates the action of antithrombin –> helps inhibit the intrinsic pathway
-unfractioned: inhibits FXa + thormbin (prolongs PTT)
- fractioned/low molecular wt: inhibits only FXa (less likely to cause bleeding)

217
Q

MOA of rivaroxaban

A

Factor Xa inhibitor - affects initiation of thrombin generation

218
Q

MOA of aminocaproic acid

A

Competitive inhibitor of plasminogen (acts like lysine) –> prevents fibrinolysis

219
Q

What is hemophilia C? Predisposed breeds?

A

Factor IX deciciency - this factor is needed to amplify coagulation (via. thrombin) and activate fibrinolytic inhibitors –> excessive fibrinolysis
Kerry blue terriers, springer spaniel, great pyrenees, Weimaraner, cats
Autosomal recvessive

220
Q

Who is predisposed to congenital VitK dependent factor deficiency?

A

Devon rex cats

221
Q

What breeds are predisposed to factor II (Prothrombin) deficiency?

A

English cocker spaniel (deficient PT)
Boxer (non-functional PT)

222
Q

What is the primary mediator of DIC?

A

Tissue factor

ACVIM General - Imp stuff (11 decks)

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