Immunology/Blood Flashcards
(223 cards)
1
Q
What is the lifespan of a monocyte
A
3 days
2
Q
What enzymes do mast cells and basophils secrete
A
-histamine
-bradykinin
-serotonin
-eosinophilic chemotactic factor
-heparin
3
Q
Which cells secrete interferon Y (gamma)?
A
NK cells
4
Q
Which types of cells do NK cells kill
A
Anything that does not possess an MHC I molecule on the surface
5
Q
What is the lifespan of neutrophils?
A
12-24 hours
6
Q
Where are the proteins of the complement system synthesized?
A
Liver
7
Q
What is the most abundant protein inn the alternate pathway of activation?
A
C3
8
Q
What breed is predisposed to C3 deficiency immunodeficiency?
A
Brittany spaniels
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
10
Q
What is the first immunoglobulin to be secreted?
A
IgM
11
Q
What is the largest Ig?
A
IgM
12
Q
What is the most common immunoglobulin in IMHA?
A
IgG
13
Q
What is the immunoglobulin seen in intravascular IMHA?
A
IgM
14
Q
What is the 1/2 life of IgM?
A
24 hours
15
Q
What is the only antibody that can act intracellularly?
A
IgA
16
Q
What Ig coats all mucosal surfaces?
A
IgA
17
Q
What is the 1/2 life of IgE?
A
2-3. days
18
Q
What is the 1/2 life of IgG?
A
3 weeks
19
Q
What Ig constitutes 75% of the antibodies in the blood?
A
IgG
20
Q
What Ig is involved in allergic rxn?
A
IgE
21
Q
Which MHC class presents endogenous antigen to cytotoxic T-cells and NK cells?
A
Class I MHC
22
Q
Which MHC class presents exogenous antigen to T-helper cells?
A
Class II MHC
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
24
Q
What are the types of APCs?
A
Dendritic cells
Activated macrophages
Activated B cells
Activated T helper cells
25
What is the receptor for T-helper cells?
CD4+ receptor - clip onto MHC II molecules
26
What is the cytotoxic T-cell profile (TH-1)?
IL-2, IL-12
27
What is the B-cell profile (TH-2)?
IL-4, IL-6
28
What is the receptor for cytotoxic killer T cells?
CD8+ receptor - clips onto MHC I molecules
29
What is the target for metronomic chemo?
Regulatory T-cells.
30
What is the MOA of the Lyme vaccine?
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.
31
What are the fever profile cytokines?
IL-1, IL-6, TNF-a
32
What are some examples of acute phase proteins?
IL-1, IL-6, TNF-a, C-reactive protein, Amyloid-A in cats, haptoglobin
33
What are some examples of negative acute phase proteins?
Albumin, transferrin, a-lipoprotein
34
What is the CLAD immunodeficiency and what breed is predisposed?
Defective intern CD11b/CD18 prevents PMN migration out of bloodstream
Irish setter
35
What breed is predisposed to IgA deficiencies?
GSD
36
What cytokine is a eosinophil attractant? Where is it produced?
IL-5
Produced in TH2 cells and mast cells
37
What is the function of IL-1? Where is I produced?
Produced in any cell
Function: pro-inflammatory, +. APP, fever, increased IL-6, fibroblast proliferation
38
What is the function of IL-2? Where is it produced?
Produced by activated T-cell
Function: T-cell proliferation, NK cell
39
What is the function of. IL-4? Where is it produced?
Produced in TH2 cells
Function: AB class switch to IgE
40
What is the function of IL-6? Where is it produced?
Produced in RES
Function: fever + APP
41
Function of IL-10? Where is it produced?
Produced in TH2 cells
Anti-inflammatory
42
Function of IL-12? Where is it produced?
Produced in TH1 cells, macrophages
Function: stimulate NK cells + cytotoxic T-cells
43
Function of IFN-gamma? Where is it produced?
Produced in NK cells, TH1 cells
Function: B-cell class switch to IgG
44
Which cytokine is associated with fever and cachexia of chronic disease? Where is it produced?
TNA-alpha
Produced in macrophages and T-cells
Function: fever, mediates acute inflammation
45
What cytokine is associated with immunosuppression and B-cell class switch to IgA?
TGF-beta
Produced in platelets and nucleated cells
46
Where do the following T-cell receptors bind to?
-CD28
-CD3
-CD4
-CD8
-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
47
What are the B-cell receptors?
CD21, CD79, CD45
48
How do attenuated vaccines stimulate the immune system?
Stimulation of cytotoxic T-cells
49
How do carrier vaccines stimulate the immune system?
Stimulate memory cytotoxic T-cells
50
How do DNA vaccines stimulate the immune system?
Stimulate memory cytotoxic t-cells
51
How do non-infectious vaccines stimulate the immune system? What is an example of this vaccine
Rabies vax
Stimulates T-helper and B-cells but not cytotoxic T-cells
52
How do adjuvants vaccine work?
Slow release of. Ag -- lead to granuloma formation
53
What are the shock organs of dogs? Cats?
Dogs - liver and GIT
Cat - lungs and GIT
54
What type of hypersensitivity is associated with atopic individuals? What Ig is involved?
Type I hypersensitivity
IgE primes mast cells and is a chemoattractant for eosinophils
Atopic individuals are TH2 polarized
55
What is the effect of alpha agonists on the regulation of mast cell degranulation?
Positive effect -- ex: norepinephrine, phenylephrine
56
What is the effect of beta agonists on the regulation of mast cell degranulation?
Negative effect -- mast cell "stabilizer" -- ex: epinephrine
57
What is a type II hypersensitivity?
-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
58
What type of hypersensitivity is associated with immune complex diseases (Arthus reaction)? What are some examples?
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
59
What is a type IV hypersensitivity rxn?
Delayed reaction involving memory T-cells
Ex: tuberculin rxn - inflammation 24-72H
60
What is the defect in SCID (severe combined immunodeficiencies)? What breeds are associated?
Autosomal recessive loss of T and B-cells
Horses, Jack russels
X-linked in bassets and Welsh corgis
61
What breed is predisposed to lethal acrodermatitis? What is the deficiency>
T-cell deficiency
Bull terriers
62
What breed is predisposed to pneumocystis carina pneumonia?
Dauschunds
63
How does FeLV/FIV lead to immunodeficiency?
CD4+ Th-cell deficiency and lymphopenia w relative normal B-cells
64
What breed is predisposed to cyclic neutropenia?
Grey coated collies
65
What is the action of NK-kB?
Increase expression of anti-apoptotic genes
66
What breeds are predisposed to pyruvate kinase deficiency? What is the sequelae?
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
67
What breeds are predisposed to PFK deficiency? What is the mode of inheritance? What is the sequelae?
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
68
What breed is predisposed to vWFD type 1? type 2? type 3?
Type 1- doberman
Type 2- German shorthaired, wire-haired pointer
Type 3- Scotties, shelties
69
How do you diagnose vWFD?
Type 1 and 3 (quantitative) -- plasma vWF antigen concentration
Type 2 - platelet function analyzerH
70
How can you treat vWFD?
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)
71
What is the MOA of plavix?
P2Y12 receptor antagonist (ADP receptor antagonist)
72
What is hemophilia A?
Deficient factor VIII
x-linked recessive, primarily affects males
73
What is hemophilia B?
Deficient factor IX
x-linked recessive, primarily affects males
74
How do you diagnose hemophilia A? B?
Both will have prolonged PTT or ACT with normal PT
Definitive diagnosis via measurement of coagulation factor activity
75
What is hemophilia C?
Factor XI deficiency
Kerry blue terriers, springer spaniels, great pyrenees, Weimaraner, cats
76
What is hageman trait?
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
77
What is the lifespan of a RBC in dog? Cat?
Dog - 100 d
Cats - 70d
78
What spherocyte count per HPF is diagnostic for IMHA? Suspicious?
Diagnostic: >=5/HPF
Suspicious: >=3/HPF
79
What integrin does the OSP of Borrelia share similarities?
Integrin CD11a/18
80
What cancer is associated with myasthenia gravis?
Thymoma
81
What cancer is associated with ITP?
Multiple myeloma
82
Degenerative myelopathy is linked to which MHC molecules?
DLAs - A3, A7, A10
83
Antinuclear antibodies causing immune diseases are linked to what?
DLA-12
84
SLE is associated with what MHC molecule?
DLA-A7
85
Myasthenia gravis in Newfies is linked to what?
MHC1
86
What antibiotic has an association of causing an immune mediated disease in Dobermans? What immune mediated disease?
Sulfas
IMPA
87
What antibiotic is associated with immune mediated diseases?
Penicillin/cephalosporins
88
What medications might have an association with immune mediated disease?
Abx- sulfa, penicillin/cephalosporin
Methimazole
Phenobarbital
Fenbendazole
Griselfulvin
Promeris
NSAIDs
Vaccine (association not proven)
89
How do penicillins/cephalosporin cause immune mediated diseases?
They adhere to cell membrane - making it easier for the immune system to recognize.
90
What types of cancers have been associated with immune mediated diseases?
Lymphoma
Leukemia (including FeLV)
Hemophagocytic syndrome of histiocytic sarcoma
Bronchoalveolar carcinoma
Soft tissue sarcoma
Thymoma
MM
91
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
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
What are signs of hemolysis per the consensus of IMHA? How many are needed to make a diagnosis
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
What is waldenstrom macroglobulinemia?
Uncommon cancer that comes from malignant B-cells (IgM) -- causes hyperviscosity
94
What cytokines are responsible for causing cachexia in cancer?
IL-1, IL-6, TNGa, TGFb, NF-kb
95
Which cytokines are associated with the mechanism of hypercalcemia of malignancy>
PTH-rp
IL-1
IL-6
PGE 1 and 2
TGFa+b
RANKL
Osteolysis
Calcitriol
96
What can hyperglobulinemia lead to in a cancer setting?
Bence jones protein can cause light chain renal tubular casts --> interstitial nephritis
97
What are negative prognostic indicators that you can find on a CBC with lymphoma?
Anemia, neutrophilia
98
What types of cancers are associated with a severe (>70K) neutrophilic? What is the mechanism?
Dog - Lung CA, renal tumors, GI LSA, FSA, rectal polyps
Cats - Lung SCC, dermal tubular ACA
Mechanism: increase G-CSF or GM-CSF
99
What types of cancer are associated with an eosinophilia? Mechanism?
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
What types of cancers are associated with immune mediated thrombocytopenia?
Lymphoma, MM, hemangiosarcoma - more common
Also MGT, MCT, nasal ACA, FSA, histiocytic
101
What is the mechanism of hypercoagulability in MCT?
Increase heparin --> cofactor for AT III --> inactivation of factors XII, XI, X, IX
102
What is Dermatofibrosis? Who is predisposed and why?
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
What is superficial necrolytic dermatitis? What's the mechanism of why it happens?
Hepatocutaneous syndrome - associated with liver disease
- mucocutaneous junctions
Glucagon secreting tumors of liver and pancreas
Gluconeogenesis --> AA catabolism --> hypoaminoacidemia --> epidermal protein depletion
104
What cancers are associated with paraneoplastic alopecia?
Pancreatic and biliary carcinoma
Most have metastatic disease
Foot pad involvement common
105
What cancer is associative exfoliative dermatitis associated with?
Thymoma
Starts as nonpruritic scaling, mild erythema of head --> neck, trunk, limbs --> scaling gets worse --> alopecia
Mechanisms unknown
Resolved with sx
106
What cancers are associated with myasthenia grave?
Dog: thymoma, OSA, cholangiocellular CA, oral Sarcoma, nonepitheliotropic cutaneous LSA
Cats: thymoma
107
What cancers is hypertrophic osteopathy associated with? What other non-cancer diseases is it associated with?
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
What cytokines are associated with fever?
IL-1, IL-6, TNF-a --> prostaglandin E2 --> hypothalamus
109
What cancers is paraneoplastic pemphigus associated with? What breeds are overrrepresented?
Dog: thymoma, thymic lymphoma, splenic sarcoma
Cat: lymphocytic thymoma
MBD, GSD, Collie, Spaniel, Weiner dog, Lab, Poodle, Scottie
110
What is CD molecule used in flow cytometry?
CD-21 - complement receptor on B-cell and rare T-cell
111
What is the CD molecule used in IHC?
CD79a -- major part of B-cell receptor
112
What CD molecule is in almost all B-cells?
CD-20
113
What CD molecule is a major part of T-cells?
CD3
114
What is the CD molecule for T-celper cells?
CD4
115
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?
CD5
116
What is the CD molecule in cytotoxic T-cells?
CD8
117
What CD molecule is found in acute leukemia?
CD34 - endothelial cell ligand for integrins
Present on lymphoid or myeloid cells
Absence does not rule out leukemia
118
What CD molecules do thymomas commonly express?
CD4 and CD8
> or = 10% of lymphocytes
119
What infectious disease has high evidence of being associated with immune mediated hemolytic anemia in dogs?Cats?
Dog - Babesia Gibson in fighting breeds, FL
Cat - Mycoplasma haemofelis
120
In which diseases processes can we see Coombs positive anemia that is not IMHA?
Leishmania, HW, Bartonella, FeLV
121
What's the specificity of saline auto agglutination test for IMHA?
*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
What immunotherapy can be used for tx of Bowen's disease, SCC of pinna or superficial MCTs?
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
What's the sensitivity and specificity of direct Coombs test for IMHA?
Sensitivity - 61-82% dogs, 82% cats
Specificity 94-100%
Cannot be performed if agglutination persists after washing
124
What is the ANA test for IMHA?
Anti-NUCLEAR antibody - tests for serum antibodies against nuclear material
IFA antibody test results
Sensitive, but not specific (false positive up to 20%)
125
What type of hypersensitivity do we see with SLE? What are some manifestations with SLE?
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
How do we diagnose SLE?
>2 or = separate manifestations of autoimmunity + positive ANA-titers
OR
>3 or = separate manifestations of autoimmunity even in the absence of detectable ANA
127
What breeds do we see T-zone lymphoma in? What sequelae do we see?
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
What is flow cytometry? How can it be used in immune mediated diseases?
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
What's the prognosis of amegakaryocytic IMT?
Poor - 86% mortality rate
Cannot make their own platelets
130
What would we expect to see in a normal joint fluid cytology? What % of monos? What % of PMNs?
Clear, colorless, viscous
0-3 cells/HPF
90100% monos
0-10% PMNs
131
What Ig is associated with rheumatoid immune mediated polyarthritis?
Rheumatoid factor - positive for anti-IgG antibodiesW
132
What are the types of IMPA?
Erosive: rheumatoid or periostea proliferative polyarhtitis (male neutered cats predisposed)
Non-erosive: Share pei fever, drug induced, idiopathic
133
What is the IL associated with Shar-Pei Fever? What is the mode of inheritance?
Autosomal recessive - increased IL-6 and amyloid deposits
134
What drug is associated with IMPA? What breed do we see it in?
Sulfa antibiotics
Dobermans
135
What are the types of idiopathic IMPA?
Type I- uncomplicated, most common
Type II- infections remove from joints
Type III- complicated by GIT disease
Type IV- neoplasia remove from joints
136
What would we see in the skin biopsy of a dog with pemphigus vulgaris?
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
What would we see in the skin biopsy of a dog with pemphigus folleaceous?
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
What drug can induce pemphigus folleaceous?
Thiol - binds to cell surface (antibiotics, promeris)
139
What breeds are predisposed to developing discoid lupus?
Collies, Shelties, GSD, huskies
140
What CS do we see with discoid lupus?
Lesions confined to the nasal planum -- loss of cobblestone, depigmentation
141
What is superficial necrolytic dermatitis?
AKA hepatocutaneous syndrome
Metabolic disease, not immune disease
142
What is the MOA of glucocorticoids?
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
Describe the arachidonic acid casdade
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
How much of budesonide reaches systemic circulation?
10%
90% first pass metabolism
145
What is the MOA of azathioprine?
Purine analog --> faulty DNA synthesis (S-phase)
Affects B-cells > T-cells
146
What are SE of azathioprine?
Hepatotoxicity
Myelotoxicity (limits use in cats)
Pancreatitis
147
What is the MOA of mycophenolate? SE?
Inhibits purine synthesis. Decresed B and T cell production
SE: GI, HGE, lymphopenia
148
MOA leflunomie
SE
MOA: inhibits pyrimidine synthesis. decreased both T and B cells
SE: GI (anorexia, V, melena), myelotoxin, hypotrichosis/alopecia
Pharmacokinetic drug monitoring
149
What is the MOA of cyclosporine?
Calcineurin inhibitor - inhibits T-cell activation and decreases IL-2 secretion
SE: GI, gingival hyperplasia, papillomatosism, hyperkeratosis, hirsutissm
150
What is the MOA of tacrolimus?
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
What is the MOA of sirolimus (rapamycin)? SE?
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
What is the MOA of imiquamod? Use?
Binds to and activates TLR-7 --> stimulating local innate immunity
Topical for carcinoma in situ, cutaneous LSA
153
What is the MOA of chlorambucil?
Alkylating agent - cytotoxic against B-cells
SE: minimal myelosupppression, GI (nausea, V, A)
154
What is the MOA of cyclophosphamide? SE?
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
What is the MOA of methotrexate? SE?
Inhibits folic acid synthesis results in decreased DNA synthesis in S-phase
SE: myelotoxic, GI
156
What is the MOA of cytosine arabinoside"
Pyrimidine analog inhibits DNA polymerization
Used in GME
157
MOA 5-fluoroUracil
Pyrimidine analog inhibits DNA polymerization
158
What is the consensus on thromboprophylaxis in IMHA dogs?
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
What is the use and MOA of romiplostim?
Novel approach for IMT
MOA: thrombopoietin receptor (TPO) agonist
160
What are negative prognostic indicators. for IHA
pre-existing systemic infections
hemophagocytic syndrome
thromboembolic complications
161
Where is vWF stored?
Weibel Palade Bodies - storage granules on endothelial cells
162
What cells produce vWF?
Endothelial cells
163
Where is vWF secreted?
Into sub endothelial matrix and plasma
164
What agonists release vWF?
Thrombin, histamine
165
What's the main receptor involved in vWF?
GpIb-IV-V
166
What receptors on the PLT surface are activated once vWF adhered?
GPIIb/IIIa, GPIa/IIa - binds firmly to collagen
167
What's glanxmanns thrombasthenia?
Genetic defect in GPIIb/IIIa
168
vWF is needed for aggregation of PLT at (low/high) shear rates
HIGH (arterioles)
169
What is vWF type1? What breeds are predisposed?
Low plasma vWF level
All multimers present
Mild to mod bleeding tendency
Breeds: Doberman, Poodle
170
What is vWF type 2? What breeds are predisposed?
Variable plasma vWF level
Large multimers absent
Mod to severe bleeding tendency
Breeds: GSP, GWP
171
What is vWF type 3? What breeds are predisposed?
Absent plasma vWF level
All multimers absent
Severe bleeding tendency
Breeds: Scotties, shelties
172
How do we diagnose type I vWF?
ELISA - measures amount of vWF:Ag in plasma compared to standard of 100
-70-180% normal
-50-69% borderline
-0-49% low
173
How do we diagnose type II vWF?
Qualitative assay - ELISA measures binding of canine vWF to collagen (dependent on high molecular weight multimers)
174
How do we diagnose type III vWF?
ELISA - measures amount of vWF:Ag in plasma compared to standard of 100
-70-180% normal
-50-69% borderline
-0-49% low
175
How do we prophylactically tx vWF deficiency?
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
What blood therapy can we give vWF deficient dogs?
- 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
What do alpha granules contain?
-vWF
-Coagulation factors (fibrinogen, FV, FXIII)
-Adhesion molecules (P-selectin)
178
What is the ligand that P-selectin binds to on endothelial cells and leukocytes?
PSGL-1
179
What do dense granules contain?
-ADP - PLT agonist
-Serotonin - PLT agonist
-Calcium - needed for 2ry hemostasis + PLT activation
-Short-chain polyphosphate - procoagulant + antifibrinolytic
180
What's the MOA of aspirin and NSAIDs?
Inhibit cyclooxygenese
-Aspirin: irreversibly
-NSAIDs: reversibly
Cyclooxygenase is needed for thromboxane A2 production (PLT agonist)
181
What's the binding site for coagulation factors?
Phosphatidylserine (PS)
182
What breed is predisposed to a defect in PS (Scotts syndrome)>
GSD
Also defect in microvesiculation
183
What's Basset Hound Thrombopathis
Defective CalDAG-GEF1
184
What's the MOA of plavix
P2Y12 receptor antagonist (receptor for ADP)
185
Name inhibitors of 1ry hemostasis
NO and prostacyclin (prostaglandin E12)
High concentrations of FDPs
Inhibit PLT activation
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What factors are involved in the extrinsic pathway?
Tissue factor
Factor VII
Calcium
Occurs in fibroblasts
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What factors are involved in the intrinsic pathway?
ENzyme cong factors- FXII, FXI, FIX
Cofactor- FVIII
Ca
Phosphatidylserine (PS)
OCCURS IN PLT SURFACE
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What factors are associated w common pathway?
Enzyme coag- FX, prothrombin (FII), FXII (crosslinker)
Cofactor- FV
Substrate: fibrinogen
Ca
PS
Product: fibrin
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Is FXII of the intrinsic pathway involved in initiating hemostasis?
NO -- deficient animals (Hageman trait - cats) have no clinical bleeding
Involved in fibrinolysis
190
What is the cell based model?
takes into account all 3 processes (primary hemostasis, secondary hemostasis, fibrinolysis)
Divided into initiation, amplification, propagation
191
What happens in the initiation phase
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
What is the MOA of rivaroxaban?
FXa inhibitor
193
What is the amplification phase
Accomplished via thrombin activating intrinsic pathway factors
Now happening in the PLT surface
Thrombin amplifies its own production --> fibrin formation
194
What is hemophilia A? How do we diagnose it?
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
What is hemophilia B? How do we diagnose it? How do we diagnose it?
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
What are the vitamin K dependent factors?
Factor 2,7,9,10
197
What are the vitamin K dependent inhibitors?
Protein C and Protein S
198
What is the action of warfarin?
Inhibits vitamin K epoxide reductase - needed for recycling vitK to its active form
Causes vitK deficiency (factors II,VII, IX, X)
199
Where is antithrombin produced?
Liver, duh
200
What is the action of antithrombin? What molecule enhances its activity?
Inhibits activity of most coagulation factors
Greatest effect on thrombin (IIa)
Heparin enhances activity
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Where is protein C produced?
Liver, duh
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What enzyme enhances the activity of Protein C?
Protein S
203
What is the action of bradykinin in coagulatioN?
Potent inducer of tissue plasminogen activator + stimulation of release of NO and prostacyclin (PLT. inhibitors)
204
What AA is involved in the plasmin production?
Plasminogen binds to fibrin through lysine residues - lysine is cleaved from the fibrin --> weak plasminogen binding to fibrin
205
What is the job of aminocaproid acid?
Competitive inhibitor of plasminogen (acts like lysine)
206
What can we detect w a BMBT?
Deficiencies in PLT #, deficient vWF, abnormalities in vascular integrity, abnormalities in PLT function
207
What can affect the result of the vWF:Ag concentration by ELISA test?
Sample hemolysis: falsely decrease
Severe inflammation, pregnancy: falsely increased
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What is the prothrombin time (PT) evaluating?
Extrinsic (FVII, TF)
Common (FX, FV, prothrombin, fibrinogen)
209
What is the activated partial thromboplastin time (aPTT) evaluating?
Intrinsic (FVIII, FIX, FXII)
Common (FX, FV, prothrombin, fibrinogen)
210
What is the activated clotting time (ACT) evaluating?
Whole blood
Visual clot formation
Severe thrombocytopenia can affect results
211
What are fibrinogen degradation products (FDPs) measuring?
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
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What is D-dimer measuring?
Form of FDP that can only be generated from breakdown of cross linked fibrin
Short 1/2. life - presence indicated recent (5h) fibrinolysis
213
When is a TEG considered hyper coagulable?
- Shorter R-time (faster time to start clot formation)
-Steeper alpha-angle (more rapid clot formation)
-Greater maximum amplitudeW
214
When is a TEG considered hypocoagulable>
-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
What artifacts can affect TEG?
Anemia - causes hyper coagulable tracing
Erythrocytosiis - causes hypo coagulable tracing
216
What is the MOA of heparin?
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
MOA of rivaroxaban
Factor Xa inhibitor - affects initiation of thrombin generation
218
MOA of aminocaproic acid
Competitive inhibitor of plasminogen (acts like lysine) --> prevents fibrinolysis
219
What is hemophilia C? Predisposed breeds?
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
Who is predisposed to congenital VitK dependent factor deficiency?
Devon rex cats
221
What breeds are predisposed to factor II (Prothrombin) deficiency?
English cocker spaniel (deficient PT)
Boxer (non-functional PT)
222
What is the primary mediator of DIC?
Tissue factor
223
