Immunology/haematology Flashcards
1
Q
Cyclophosphamide mechanism of action?
A
Alkylation (cross linking) of DNA in S phase.
T and B cell lymphopenia, suppresses T cell activity and AB production
Acrolein bladder tox.
2
Q
Azathioprine mechanism of action?
A
Purine analogue, metabolised to ribonucleotide monophosphates (6mercaptopurine) and inhibits enzymes required for purine biosynthesis. DNA incorporation causes RNA miscoding.
Humoral > cell mediated immunity. Decreases lymphocyte activation and proliferation (lack of purine salvage pathway). Decreases macrophage function.
Active form metabolised by thiopurine methyltransferase and xanthine oxidase.
3
Q
Relevant breeds and medications for azathioprine use?
A
Giant schnauzer/cat - low TPMT activity. Malamute - high TPMT activity. Allopurinol inhibits XO.
4
Q
Methotrexate mechanism of action?
A
Inhibits (competitive) folic acid reductase - no purine/pyrimidine synthesis. Mostly S phase.
5
Q
Glucocorticoid mechanism of action?
A
Cytosolic glucocorticoid receptors (vary with tissue), glucocorticoid response elements, gene transcription.
Stabilise endothelial membranes, decrease chemotactic factors/cytokines/adhesion molecules. Inhibit arachidonic acid release.
Dose dependent, cellular/humoral.
Decrease pro inflamm cytokines, complement function, T cell proliferation/AB production, macrophage Fc receptors
Increase anti inflamm cytokines
Redistribute mono/lymphocytes, mainly T, to bone marrow and lymphatics.
6
Q
How much mineralocorticoid activity do the various steroids have in comparison to cortisol?
A
Prednisolone 0.3 - 0.8
Dex 0
Hydrocortisone 0.8 - 1
7
Q
Cyclosporin mechanism of action?
A
Cyclosporin/cyclophilin compleex binds and inhibits calcineurin. Impedes calcium dependent signal transduction/dephosphorylation, impedes activation of nuclear factors of activated T cells. No nuclear transcription of IL2 so decreased T cell activation/proliferation.
Cytotoxic T cell activity decreased.
Stimulates TGFbeta production which inhibits IL2-stimulated T cell proliferation and generation of antigen-spec cytotoxic T cells.
NB need ultramicronised microemulsion (better absorption)
Cytochrome p450 metab, biliary excretion. Peak conc 2h
Pharmacodynamic evaluation measures IL2 and IFN gamma.
Hepato-nephrotixicity v uncommon
8
Q
Side effects of ciclosporin?
A
Secondary inf gingival hyperplasia hirsutism
9
Q
Tacrolimus mechanisms of action?
A
Similar to cyclosporin - FKbinding protein complex, decrease T cell activation.
Does B and T cells and ABs. More potent than cyclosporin.
10
Q
Mechanisms of action of sirolimus/rapamycin?
A
mTOR inhibition
(T cell G1 - S, cyclosporin G0 - G1)
T and B cells
11
Q
Mechanism of action mycofenolate?
A
Hydrolysed to mycophenolic acid by the liver (active form).
Inhibits inosine monophosphate dehydrogenase in activated lymphocytes (needed for de novo purine biosynthesis). Prevents guanosine and deoxyguanosine biosynthesis.
Inh B and T cell proliferation. Decrease AB production. Apoptosis activated T cells. Humoral and cell med immunity, decrease adhesion and lymphocyte/mono recruitment
Hepatic glucuronidation inactivates to mycophenolic acid glucuronide which is excreted in bile (intestine flora deglucuronidate so get second peak). 90 % excreted in urine as MPAG.
12
Q
Leflunomide mechanism of action?
A
Inhibit de novo PYRAMIDINE synthesis. Dihydroorotate dehydrogenase inhibitor.
B and T lymphocyte - decrease proliferation, decrease leucocyte adhesion, decrease IgG synth.
Activates by intestinal mucosa/liver to teriflunomide.
Renal excretion of trimethylfluoroanaline - susceptible tox if renal insufficiency.
13
Q
Chlorambucil mechanism of action?
A
Non cell cycle specific alkylating agent. Cross links DNA. Inhibits resting/dividing cells, esp lymphocytes - cell and humeral immunity inhibition.
Inactivated by the liver
14
Q
How are RBCs destroyed in extravascular/intravascular haemolysis?
A
Extra - macrophages in spleen
Intra - complement mediated - IgM ABs activate
Antierythrocyte ABs from B cells, but T cell (CD4 driven disease)
15
Q
What genetic factors are there for development of IMHA?
A
Breed - cocker spaniel, familial association
Autoreactive T cells in siblings
DLA haplotype?
16
Q
Most common antigen in IMHA?
A
Anion exchange molecule/erythrocyte membrane glycoproteins
17
Q
What seasons is IMHA most common in?
A
Spring and early summer
18
Q
Percentage of idiopathic IMHA?
A
70 - 80 %
19
Q
What antibodies are most common canine IMHA?
A
IgG or IgG plus IgM (rare to have only IgM)
20
Q
Increased pro-inflamm cytokines IMHA?
A
Monocyte chemoattractant protein 1, GMCSF (assoc with mortality also IL15 and 18)
21
Q
Why might thromboembolism occur in IMHA?
A
DIC - evidence present 50 %
22
Q
What do platelets express more of in IMHA?
A
P-selectin - activation (driven by cytokines)
23
Q
Negative prognostic indicators canine IMHA?
A
Hyperbilirubinemia, thrombocytopenia, leucotyosis with left shift, azotaemia, hypoalbuminaemia, intravascular haemolysis, prolonged hyperlactataemia hepatic insufficiency, macrophage activating cytokines, autoagglutination, increased aPT.
24
Q
What is NOT associated with IMHA outcome?
A
Degree of anaemia, magnitude reticulocyte response (1/3 present non-reg), degree of spherocytosis
25
Why would you use LMW and not unfractionated heparin?
Latter more likely to cause iatrogenic coagulopathy (thrombin and Xa). LMW less protein bound and more stable pharmacokinetic.
26
Mechanism of heparin action?
Binds AT, enhances its activity, inhibit factor II and X. CRI required for efficacy?
LMW only does Xa not thrombin. Need to monitor this factor to assess efficacy, can't use aPTT.
Variable between individuals, goal appt 1.5 - 2.5 x RI
27
Does ultralow dose aspirin have an anticoagulant effect?
Not in healthy dogs. Single 5 - 10 mg/kg dose inhibits platelet function in healthy dogs.
BUT ultralowdose aspirin was associated with improved outcome in dogs with IMHA.
28
Clopidogrel target?
Platelet P2Y12 (ADP receptor) - block aggregation
29
Survival benefit of aspirin versus clopidogrel IMHA?
No difference, even if clopidogrel loaded. No difference if drugs added together.
30
Benefits of glucocorticoids in IMHA?
Suppress macrophage function
| Decrease T cell activity (therefore decrease B cell stim and AB production) and induce lymphocyte apoptosis
31
Evidence for secondary immunosuppressive drugs in IMHA?
One study found superior survival with azathioprine, otherwise no evidence to add secondary
32
Platelet count in greyhounds?
Can be lower than other breeds
33
In what infectious diseases have anti platelet antibodies been detected?
Ehrlichia canis, Rickettsia. rickettsii (RMSF), A phagocytophilum, Babesia, Lepto, Leishmania
34
Most likely causes of moderate to severe thrombocytopenia?
ITP, overwhelming sepsis, E canis
35
RBC life span in cats and dogs?
70/120 days
36
Indirect/direct platelet autoantibody?
Indirect - AB in serum, direct - AB on platelet/megakaryocyte surface
Direct more specific
37
When is splenectomy contraindicated in ITP?
Haemoparasite infections - can exacerbate and associated with resistance antiprotozoal therapies.
38
ITP negative prognostic indicators?
Severe bleeding with anaemia, intracranial haemorrhage, melaena/increased urea
NOT platelet count
39
Most common antigen in ITP?
Fibrinogen receptor (GPIIb/IIIa)
Decrease in Treg cells implicated
40
ITP associated with recent vaccination?
NO!
| one case report distemper
41
What Ig is on platelet in ITP?
IgG (present in 77 % ITP, 100 % B gibsoni...)
Increases with age of sample
42
Evidence for secondary therapies in ITP?
IVIg and vinc equally shorten time to platelet recovery and hospitalisation
One case series mycophenolate mono therapy
No evidence for other secondary agents
43
Platelet decrease significance in IMHA?
< 50, 76 % mortality 30 d
| < 15, 25 % mortality (not different IMHA alone)
44
Cats and IMT?
Only around half respond to pred alone - need secondary. Frequent relapse. Long term immunosuppressive.
45
What influences BMBT other than platelet number and function?
Haematocrit, blood viscosity
46
What PFA time is best for vWD?
Collagen/ADP, > 120 s
Also impacted by BMBT factors
47
What % of vWF is normal?
70 - 180 %, < 50 abnormal
48
What might falsely increase and decrease vWF?
Decrease - haemolysis
Increase - pregnancy/parturition/inflammation/sepsis
49
Type 1 vWD?
Partial quantitative deficiency - Doberman, Irish setter. GSD, BMD - all same mutation, autosomal recessive
50
Type 2 (A) vWD?
GSH/WHP, collie, Chinese crested Auto recessive
Loss HMW protein, need to demonstrate decrease collagen binding activity (ratio with Ag:binding >1)
51
Type 3 vWD
Complete lack of factor. Dutch koiker, scottie, sheltie.
Auto recessive, various mutations
52
Inheritance pattern of congenital coagulation factor deficiencies?
Haemophilia A and B (8 and 9) X linked recessive
I, II autosomal
VII, X, XI, XII autosomal recessive
53
Changes in clotting times with coagulation factor deficiency?
PTT and PT: I, II, X
PT: VII
PTT: VIII, IX, XI, XII
54
Do dogs have vWF in their platelets?
No, only endothelium
55
Does factor activity influence clinical severity in canine type 1 vWD?
Controversial - one source says yes one says no
56
What haemophilia is most common? What haemophilias affect breed/species?
Dogs and cats. A most common. Many breeds.
57
What percentage of factor activity correlates with most bleeding in haemophilia?
Severe < 2 %, mild to moderate 2 - 20 %
Normal = 50 - 150
58
Breeds for congenital factor I deficiency?
Fibrinogen - dogs (borzoi, collie, bichon) and cats
59
Breeds for congenital factor VII deficiency?
Initiates coagulation by interacting with tissue factor.
Beagles, deerhounds (same mutation) - mild.
More severe malamutes and cats.
60
Breeds for congenital factor XI deficiency?
Kerry blue, springer, cats
Mild haemorrhage
61
Breeds for congenital factor XII deficiency?
Haegman. Cat. Activates intrinsic pathway in vitro not required for fibrin formation in vivo. No clinical consequence.
62
What are the labile clotting factors?
V and VIII
63
What is in cryoprecipitate?
vWF, VIII, I, fibronectin, XIII
64
What is in cryosupernatant?
Everything but vWF, VIII and I
65
How does tranexamic acid work?
Antifibrinolytic. Lysine analogue, inhibit plasmin activation.
66
What is the main stimulus for thrombin formation in DIC?
Tissue factor:VIIa complex. Activates factor IX (intrinsic) and X (common pathway)
67
How might DIC occur in systemic inflammation?
Monocytes express tissuee factor, anticoagulant system impaired, PAI-1 (plasminogen activator inhibitor) mediated fibrinolysis inhibition,
68
What does antithrombin inactivate?
II, TF:VII, IX, X, XI
Also binds cellular receptors on neutrophils/monos, stim antiinflamm/antiplatelet prostacyclin production
AT depletion (consumption in AT thrombin complex, degradation by neutrophil elastase, decreased hepatic synthesis, loss due to capillary permeability) factor in DIC
69
When should DIC be anticipated
Hypotension, impaired organ blood flow, SIRS, vasoactive agent release
70
What is a sensitive test for DIC?
D - dimer - 95 % sensitive
71
How does the endothelium protect against thrombosis?
Thrombomodulin binds thrombin and allows it to activate protein C, C associates with S.
CS: inactivates V and XIII
Endothelium produces prostacyclin under thrombin influence - inhibits platelet aggregation.
Tissue plasminogen activator causes fibrinolysis.
72
How might fibrinogen change haemostasis?
Increased in inflammation. Increases blood viscosity and RBC aggregation - decreased blood flow. Increases velocity of platelet aggregation and increases platelet reactivity. Denser clots, more resistant to fibrinolysis.
73
Why might aspirin be ineffective in dogs?
Aspirin acts through decreasing thromboxane A2 formation and therefore increasing platelet activation for its lifetime. Thromboxane is G protein mediated and 70 % normal dogs have a defect in the G protein signalling.
74
High dose or low dose aspirin for ATE in cats?
Low dose is fine as no diff in recurrence, fewer GI effects
75
What factors might affect TEG/ROTEM?
Hypocoag - increased PCV/decreased platelet
| Hypercoag - decreased PCV/increased fibrinogen, storage
76
How sensitive are PT/aPTT?
Need factor activity to be decreased by 30 - 50 % to be abnormal
77
What affects PT?
Tissue factor (extrinsic) and common pathways.
VII, X, V, II, I
78
What affects aPTT?
Contact (intrinsic) and common pathway.
VIII, IX, X, V, II, I.
79
What would you measure with the Clauss method?
Fibrinogen.
Could also measure with thrombin time.
80
What is the difference between FDP and D dimers?
D dimers are only present if there has been fibrin crosslinking.
D dimers have short half life approx 5h.
81
Why is thrombin antithrombin ELISA measurement useful?
Thrombin has a short half life, TAT stable. Increased HAC/neoplasia/blastomycosis.
82
Why are animals with IMHA hypercoagulable?
RBC membrane phosphatidylserine exposed.
Monocytes express tissue factor.
Systemic inflammatory state increased platelet reactivity.
83
What are most IMHA deaths causes by?
Thrombosis, pulmonary most common
84
Does albumin correlate with risk of thrombosis in PLN?
PLN - other factors for hypercoag other than AT - platelet reactivity/fibrinogen increase/fibrinolysis decrease.
Albumin might be a marker of thromboembolic risk but doesn't always correlate with hyper coagulability and AT. Can be hypercoag with normal albumin.
14 - 27 % PLN get thrombosis
85
PLE and thrombosis?
Decreased AT and evidence of hypercoagulability. Clinical thrombosis low but unpredictable - can happen when improving.
86
What is the most common cause of PTE?
Neoplasia
87
What enzyme do anticoagulant rodenticides inhibit?
Vitamin K epoxide reductase (reduces vitamin K epoxide so it can act with gamma glutamyl carboxylase to carboxylate clotting factor precursors)
88
Vitamin K dependent clotting factors? One with shortest half life?
2, 7, 9, 10, protein C and S
7 shortest half life
89
When does PT change after rodenticide intox?
36 - 72h
PIVKA at 12h
90
What are acquired anticoagulants?
Antibodies directed against clotting factors, usually IgG.
Example - lupus anticoagulant - antiphospholipid protein AB - inhibits coag factor/cell membrane interaction - increased PTT
91
Scott syndrome?
GSD, lack of externalisation of phosphatidylserine - get coagulopathy as membrane surface cannot support plasma coagulation factor activity
Autosomal recessive.
Get epistaxis not petechia/ecchymoses. Prothrombinase activity required for nasal arterial microcirculation?
Flow cytometry can measure PS externalisation
92
How would the corrected reticulocyte count be calculated?
Divide retic count x hct by normal hct
93
How long does it take for a rbc precursor to develop through to RBC?
5-7d
94
How long do reticulocytes stay in the bone marrow for?
2-3d
95
What effect does EPO have on the cell red composition?
More retics and latestage polychromatophilic erythroblasts (normoblast)
96
What result would you expect from Coomb's/osmotic fragility test in haemophagocytic syndrome?
Negative both
97
Why does hypophosphataemia cause haemolysis?
Decreased membrane stability (interference with energy metabolism), so more osmotic fragility and susceptibility to oxidative stress.
98
When would a Coomb's test be positive in Babesia?
Gibsoni/vogeli
99
Most sensitive test for Babesia?
PCR
100
Retroviruses and mycoplasma?
Increased risk for mycoplasma
101
When do anti-erythrocyte antibodies develop in mycoplasma infection?
After the onset of anaemia
102
Pyruvate kinase deficiency?
Autosomal recessive, progressive iron overload might cause haemosiderosis/hepatic fibrosis.
Can occur in cats and dogs. Cats dx old dogs young.
DOGS - progressive myelofibrosis due to iron overload./prolonged haematopoiesis.
103
Phosphofructokinase deficiency?
Springer spaniels. Autosomal recessive. Not cats.
Exacerbated by exercise (alkalaemia - haemolytic crisis)
104
What markers are usual for histocytic sarcoma?
CD 11 and CD 18
Macrophage derived
105
Where is EPO made?
Peritubular interstitial cells under the influence of hypoxia inducible factor
Also liver - may be increased with hepatic injury
106
What might increase hepcidin?
Positive acute phase protein so IL6, also decreased renal clearance can increase
107
Transferrin?
Negative APP, TIBC
108
Iron deficiency saturation percentage?
Iron/TIBC < 20 %
109
What is important about EPO analogues?
Aim low end RI to minimise hypertension, have to give iron concurrently.
Darbo give less often, and less likely to form antiEPO ABs, but more expensive.
110
What hormones stimulate erythropoiesis?
T4, glucocorticoid, growth hormone
111
How should a polycythaemic dog with a concurrent PDA be managed?
PCV maintained higher due to hypoxaemia
112
GPIIIb/IIa?
Fibrinogen receptor
113
GPIb?
vWF receptor
114
GPVI?
Collegan receptor on platelet
115
Where is thromboxane A2 from?
Phospholipase A2 in platelet > arachidonic acid on activation > COX 1 makes into thromboxane A2
116
Alpha granules platelet?
Some vWF in cats, fibrinogen, factor V/XII, P selectin
117
Dense granules platelet?
ADP, calcium, serotonin
118
Does DDAVP increase HMW vWF?
Increases vWF a little in type 1 but not more HMW in dogs
119
Acquired vWD?
CKCS with mitral valve disease (decrease factor and loss HMW multimer),
Also SAS
120
vWD in cats?
Both type 3 in case reports
121
Greater Swiss mountain dog platelet disorder?
P2Y12 receptor - impairment of ADP binding.
Autosomal dominant. No spontaneous bleeding.
122
Glanzmann thrombasthenia?
Otterhound and Great Pyrenees, two different mutations, autosomal recessive.
Absence of the fibrinogen receptor (GPIIb/IIIa) - get spontaneous bleeding.
Also described in a male cat with integrin subunit alpha IIb gene mutation.
123
CaIDAGGEFI thrombopathia?
Prevents GPIIIb/IIa conformational change for fibrinogen binding. Spontaneous mucosal bleeding.
Basset, spitz, landseer. Recessive.
124
Cyclic haematopoiesis?
Grey collie. Autosomal recessive.
Cyclic neutropenia/stem cell deficit. Defect trafficking lysosomal membrane proteins. Neutrophils deficient in neutrophil elastase and myeloperoxidase.
Platelet storage pool disorder - serotonin/ATP/ADP deficiency (dense granules).
Cannot phosphorylate intracellular proteins so lack of platelet activation by collagen, thrombin etc.
125
LAD I/II?
GSD, impaired integrin activation on platelets.
126
Chediak Higashi syndrome?
Lack of dense granules in platelets.
Recurrent neutropenia with neutrophil function defects.
Leucocyte/melanocyte abnormalities. Persian (blue smoke). See abnormally fused granules in neut/eos/other cells.
C-GSF might partially correct neutrophil function.
127
Platelet delta storage pool disease?
Platelet dense granule ADP deficiency - Am cocker spaniel.
Increase ATP:ADP ratio in platelets.
128
What product is useful in Scott syndrome?
Cryopreserved platelets as they have externalised phosphatidylserine
129
What might look like Chediak Higashi syndrome on a blood smear?
Birman granulation anomaly, toxic neuts, mucopolysaccharidosis.
130
Pelger Huet anomaly?
No functional implications. Defective granulocyte maturation. Hyposegemented nuclei.
Autosomal dominant with incomplete penetrance (heterozygotes = embryonically lethal). Australian Shepard.
131
What might mimic Pelger Huet anomaly?
Inflammation/infection/myelodysplastic syndromes
132
Leucocyte. adhesion deficiency?
CD18 integrin deficiency - leucocyte adhesion protein mutation. Irish setter. Marked neutrophilia, susceptible to infection, die at 2-3m.
133
Trapped neutrophil syndrome?
Autosomal recessive, border collie.
BM myeloid hyperplasia with peripheral neutropenia.
Craniofacial deformities?
134
X linked severe combined immunodeficiency?
Cardigan corgi/basset
Mutation in IL2 gene. Affected developing lymphocytes (CD 4 and 8 neg) in the thymus. No T lymphocytes. Get non-functional and B over time.
135
Autosomal recessive combined immunodeficiency?
JRT, defective recombination events during T and B lymphocyte maturation. Decreased lymphocytes and globulin.
136
Common variable immunodeficiency?
CKCS/mini Dachs
P carini due to absence of B cells/decreased globulin
137
How might you diagnose immune mediated neutropenia?
Flow cytometry for anti-neutrophil ABs, is sensitive and specific.
Granulocyte agglutination and immunofluorescence is not sensitive or specific.
138
What bone marrow changes would suggest primary myelodysplastic syndrome over secondary dysmyelopoiesis?
Increased immature precursors, higher percentage of dysplastic cells, megaloblastic erythroid precursors.
Differentiate from chronic myeloid leukaemia as no circulating myeloid cell increase
NB secondary due to sepsis - increased blast in recovery)
139
MDS excess blasts?
Most common one in dogs and second most common in cats.
Pancytopenia, increase myeloblasts (up to 20 %) in bone marrow, dysplasia in all three cell lines, asynchronous maturation.
Many cat with this are FeLV pos.
Poor px
140
MDS refractory cytopenia
Older dogs, insidious onset, only red cells. Hyper or normocellular bone marrow, erythroid hyperplasia/dysplasia, rubriblasts may be up to 30 % of nucleated marrow cells.
In cats - other cell lines also affected (is this actually refractory cytopenia with multilineage dysplasia?
141
MDS refractory cytopenia with multilineage dysplasia?
Cats, FeLV, dysplasia two cell lines with < 5% myeloblasts
142
What causes secondary dysmyelopoiesis?
IMT, IMHA, PRCA, neoplasia
Chemo drugs, leishmaniasis, oestrogen
143
Secondary myelofibrosis?
PK deficiency most common.
Also necrosis, FeLV, drugs, toxins, rhEPO
144
Myelonecrosis?
Ischaemia, IMHA, sepsis, neoplasia, drugs
145
Lyophilised platelets?
Non-inferior to cryopreserved platelet concentrates. for management of bleeding in thrombocytopenic dogs.
146
What improves slide agg specificity for IMHA?
Dilution with saline, but sensitivity decreases. 1:1 29 % spec, 88 % sens
147
GSH, ROS and vit E in anaemia?
GSH decreased in anaemia, lower in non-haem than haemolytic, no diff ROS/vitE
148
Does pRBC transfusion affect TEG in dogs?
Only minimally. Decrease MA/clot strength
149
What affect would tranexamic acid have on TEG?
Increased MA, decreased percentage clot lysis
150
What blood group naturally occurring alloantibodies might dogs have?
DEA 3, 5 and 7
151
Mean platelet component in IMHA?
Lower and associated with mortality.
152
Prevalence of DEA 4 antigen?
> 90 %
153
Can RBCs be cryopreserved in glycerol?
No
154
Is clopidogrel generic equivalent to Plavix in cats?
Yes for plasma conc and active metabolite
155
Why would hypocobalaminaemia cause anaemia?
Decreased purine/thymidylate synthesis, impaired erythroblast DNA synthesis, erythroblast apoptosiss
156
Why are cats susceptible to Heinz body formation?
More oxidisable sulfhydryl groups, lower intrinsic antiox activity, lack of N-acetyltransferase 2 so paminophenol produced and methemoglobin production perpetuated.
157
Cat breeds reported for porphyria, erythrocyte osmotic fragility and PK deficiency?
Porphyria - Siamese, DSH
EOF - Abyssinian, DHS, Somali
PK - Abyssinian, Somali, Bengal
158
Punctate or aggregate retics relevant for assessing regeneration?
Aggregate (they mature to punctate in cats)
159
Cats with breed specific RI for Hct/retic count?
Birman, Norwegian forest cat and Siberian, Maine coone
160
RBC markers of iron deficiency?
MCV/MCHC, but insensitive - retic Hb content better
161
BM findings in PRCA?
Reduced/absent precursors.
Normocytic/normochromic anaemia. No other cytopenias.
162
BM in non reg IMHA?
Marked erythroid hyperplasia and low myeloid:erythroid ratio.
May be maturation arrest.
Often dysplasia/fibrosis/necrosis.
Circulating normo- or macrocytic (latter due to agglutination) RBCs, often neutropenia or decreased platelets.
Other criteria for dx:
Pos DAT/slide agg/ghost cells
163
BM in aplastic anaemia?
Reduction/absence of haematopoietic tissue with replacement by fat. Bi/pancytopenic.
164
When would you have secondary myelodysplastic syndrome?
Chemo or radiation.
165
What would a bone marrow increase in reticulin fibrosis indicate?
Myelofibrosis
166
What is menatetrenone and what might you use it for?
Vitamin K2 analogue, promotes cell differentiation, use feline MDS
167
What does vitamin D do to hepcidin?
Inhibits production
168
Prevalence of naturally occurring ABs against dog erythrocyte antigens in cats?
High prevalence based on major crossmatch
169
PFA100 in anticoagulant treatment in cats?
Detects changes in healthy cats treated with clopidogrel but not aspirin.
170
When is remission seen in non reg IMHA in cats?
Around 40 - 60 days. No difference outcome PRCA/NRIMHA. Remission reported with steroids alone, cyclosporin alone, steroids plus cyclosporin, steroids plus chlorambucil.
171
What happens to feline RBCss when you store them?
Haemolysis and ecchinocytosis
172
How would hyperfibrinolysis look on ROTEM?
Late, weak clot formation
173
What DEA antibodies do Cane Corsos have?
Anti-DEA 7
174
Rivaroxaban mechanism of action? How to monitor?
Xa inhibitor.
Monitor with PT and (peak reaction time) R value of TEG - aim 1.5 - 1.9 x
175
Agreement between D dimer assays?
Poor.
176
Does TEG predict thrombosis in dogs?
Not well.
177
How may you therapeutically induce Treg cells?
Low dose IL2 tx - Treg express IL2 receptor
178
Cyclophosphamide in IMHA tx?
Poorer outcome in two studies
179
Macrothrombocytopenia?
CKCS and Akita
180
What happens after xenotransfusion?
Haemolysis 1 - 6 d, haemolytic transfusion reaction (delayed) in 64 %
181
Crossmatching cats pre-transfusion?
Some studies say improved post transfusion increase in PCV. Incompatibilities frequent even in naive cats (15 %). Less febrile transfusion reactions in crossmatched cats.
This has not been consistently documented.
Older blood products may impact survival.
182
What inhibits fibrinolysis?
Tissue plasminogen activator inhibitor, alpha 2 antiplasmin and thrombin activatable fibrinolysis inhibitor
183
What does normal APTEM with increased clot lysis on EXTEM mean in terms of ROTEM?
Hyperfibrinolysis
184
Suggested mechanism for greyhound hyperfibrinolysis?
Decreased alpha2 antiplasmin
185
Angiostrongylus coagulopathy?
vWF deficiency, hyperfibrinolysis, DIC
Decreased fibrinogen/hyperfibrinolysis on ROTEM
186
Dirofilaria immitis coagulopathy?
Hyperfibrinolysis - directly stimulates plasmin production - hyperfibrinolysis
187
What happens when you add omega 3 to aspirin tx?
More inhibition of platelet function. no impact omega 3 alone
188
Which disease has lower platelet and WBC - Ehrlichia or leishmania?
Ehrlichia
189
Cyclosporine or mycophenolate for IMT in dogs?
Equal response - less SE myco
190
What happens to ammonia and lactate when you store pRBC? Glucose/Na/Cl/K?
Increased lactate/ammonia, increased sodium and chloride, decreased glucose and potassium
191
Comparison between dogs with amegakaryocytic thrombocytopenia and primary IMT?
Amegakaryocytic more severe and worse px
192
What does it indicate if anti platelet antibodies recur in IMT patients?
Increased risk of relapse. But persistence not associated with treatment response.
193
What pRBC are best for IMHA?
Fresh, no more than 7 - 10d as increasing age increases mortality/risk of transfusion reactions.
194
Response rate of pred alone in IMHA?
80 %, no evidence dexa superior
195
Evidence for secondary drug in IMHA?
Azathioprine might be assoc with better outcome - not uniform through studies
Ciclosporin - never any difference in survival found
Mycophenolate - compared to aza or ciclosporin - no difference
IVIG - no effect on survival compared to aza - but more rapid recovery of pcv or less transfusion requirement maybe?
196
When do hepatotoxicity and myelosuppression occur with azathioprine?
First few weeks hep, can be months BM.
GSD more susceptible hepatotoxic?
197
Ciclosporin liver effects?
Uncommon idiosyncratic hepatotoxicosis
198
When is thromboprophylaxis particularly important in IMHA?
Intravascular haemolysis, autoagglutination, marked leucocytosis, increased hepatic enzyme activity
199
Anticoagulant drugs for IMHA?
Longer survival if individual unfrac hep dose cf non-individualised
No diff clopidogrel versus rivaroxaban - latter better for fibrin rich venous thrombosis?
200
Canine familial methaemoglobinaemia?
Pomeranian, CYB5R3 mutation. this is the NADH cytochrome B5 reductase gene. Encodes methemoglobin reductase.
Probably recessive.
Treat with methylene blue.
(ascorbic acid/riboflavin?)
201
Other than IMHA, what might cause an abnormal osmotic fragility test?
Hyperlipidemia, age of erythrocyte, congenital membrane abnormalities
202
What can cause spherocytes other than IMHA?
Oxidative damage, hypersplenism, PK deficiency, erythrocyte fragmentation, spectrin deficiency (if > 24h old)
203
How many drops of saline should you add to blood for. slide agg?
4 drops - 100 % specific
204
Are tests for IMHA affected by transfusion?
Probably - DAT, spherocytosis and SAT
205
Criteria to support hyperbilirubinemia?
> 2 urine dipstick dog, icterus, increased in blood, any in urine cat
206
What Babesia species is most associated with IMHA?
Gibsoni most evidence
Also canis, rossi and vogeli
(Small > large)
Immunosuppression should not be required - due to damage to cell membranes/exposure of epitopes act as antigens
207
What infections cause DAT pos?
Leishmania, D immitus, Bartonella
208
Anaplasma cause IMHA?
Maybe - phagocytophilum and platys
209
Babesia and IMHA in cats?
Yes - B. felis, tx resolves without immune supp
210
Pathogenesis of mycoplasma and IMHA
Similar to Babesia
211
Babesia conradae?
California, coyote hunting dogs - no serological test available do PCR
212
What does FIBTEM measure?
Fibrinogen (Max clot firmness)
213
Clinical significance of methemoglobinemia?
Oxidation of ferrous iron to ferric iron, can't bind O2, cyanosis and impaired aerobic resp. Causes allosteric interaction and left shift dissociation curve (decreased release O2)
214
How does NMB treat methemoglobinemia?
NADPH reductase converts to leukomethylene blue, which reduces methemoglobin to Hb
215
Cell free DNA in IMHA?
Neutrophil extracellular traps - might increase hypergoag
216
What breeds might be Dal negative?
Dalmation, doberman, Shih tzu
V prevalent in other breeds, might be hard to find Dal neg donor
No naturally occurring AB though, just post transfusion
217
What types of Kai positivity can dogs have?
Neg 1 and 2 or pos for 1 or 2. Pos 1 most common. Unrelated to Dal, 1, 3, 4 and 7
218
HCM Maine Coones and hypercoagulability?
A31P mutation in myosin binding protein C (MYBPC3) - increased P selectin, platelet derived microvesicle and platelet endothelial adhesion molecule 1 expression,
Clopidogrel attenuates in most but not all cats
219
What does cyclosporin do to thromboxane synthesis?
Increases - inhibited by aspirin
220
How might glanzmann thrombasthenia occur?
Defect in gene encoding GPIIb or GP IIIa - ONLY FORMER IN DOGS
221
Negative prognostic factors for IMHA in cats?
Increased bilirubin, age
| Decreased globulin, lymphocyte
222
How might cyclosporin promote oncogenesis?
Promote angiogenesis, inhibit DNA repair and apoptosis, promote TGFbeta synthesis
223
How does IVIG work?
Modulate macrophage Fc receptors expression and function, decrease B/Tcell activation, interfere with complement action, decrease Ig production
224
What is the most common bacterial type to cause septic arthritis?
Gram positive aerobes
225
Infectious causes of polyarthritis?
Any Ehrlichia, Borrelia, Anaplasma phagocytophilum, R ricketsii, Mycoplasma, L form bacteria, leishmania
FeLV cat
226
Mycoplasma species and polyarthritis?
Cat felis/gatae, dog spumans
227
L form bacteria?
Lost cell wall, need special culture/electron microscopy
Subq abscesses in cats and dogs, and polyarthritis
228
Pathophys of fungal disease and joints?
Can be either direct involvement or secondary IMPA (latter more common)
229
Calicivirus vaccine?
Can cause short duration mononuclear joint inflammation in kittens
230
How would steroids affect mucinosis?
Decreased hyaluran synthase activity decrease hyaluronic acid in skin
231
Hypersensitivity in IMPA?
Type III - Ag/AB deposition
232
Ddx for IMPA?
Panosteitis, hypertrophic osteodystrophy
233
Criteria for IMPA diagnosis?
> 10 % neuts in >1 joint
234
How many IMPA fail to respond?
10 %
235
Do concurrent DEA 1.1 1.2 positive dogs exist?
No - but can negative for both
236
What group has Dal antigen commonly negative?
Dalmatian - paradoxic...
237
False positive DEA 1.1?
Weak 1.2, autoagglut
238
AB allele interaction with a and b?
AB recessive to A and codominant to b
239
What mutation to type B cats have?
No conversion of Nacetylneuraminic acid to Nglycolylneuaminic acid
240
What are type B alloantibodies
Antibodies in B cats against A antigen; haemolysins and haemagglutins, mostly IgM lesser IgG
241
What happens if you give Mik pos blood to a Mik neg cat?
Acute haemolytic transfusion reaction
242
Difference between granulocytic and monocytic Ehrlichia?
Monocytic more likely to develop chronic/subclin after doxycycline - thrombocytopenia and nonreg anaemia
243
Anaemia in FeLV
Macrocytic non-reg
244
GCSF in FIV?
Increases viral load.
Coinf with FeLV - more cytopenias
245
PRCA FeLV in cats?
Subgroup C
246
Causes of aplastic anaemia in dogs?
Ehrlichia canis, parvo, drug tox, radiation, idiopathic.
Bi/pancytopenia and 95 % marrow is adipose
247
Myelonecrosis in cats and dogs?
Dog - drugs, immune mediated disease, neoplasia, sepsis
Cats - nonregIMHA, FeLV, myelodysplastic, leukaemia
Good px dogs variable cat
248
Benign haemophagocytic syndrome?
Bi/pancytopenia and more than 2 % benign haemophagocytic macrophages in bone marrow - exclude myelonecrosis myelofibrosis and marrow inflammation as these can cause the macrophage appearance
Dogs - IMHA SLE sepsis E canis fungal neoplasia myelodysplastic, 20 % idiopathic
249
Cut off myeloblasts to distinguish myelodysplastic syndrome from leukaemia?
20 %
250
Px better refractory anaemia or refractory anaemia with excess blasts?
Former - and also less ill
Latter bi/pancytopenia and dysplasia in all cell lines
251
Types of feline erosive arthritis?
Periosteal proliferative - marked, FeLV/FIV
Minimal new bone - rheumatoid
252
Features of rheumatoid arthritis?
Subchondral bone lysis, articular cartilage loss, erosion of periarticular bone, joint deformation and ligament destruction
253
What is rheumatoid factor?
Auto antibody against IgG, has role in opsonising and clearing immune complexes (may be increased in any inflammatory disease), 70 % sensitive - use for monitoring?
254
Treatment for feline rheumatoid arthritis?
Methotrexate + leflunomide
255
Criteria for SLE diagnosis?
Three manifestations of autoimmunity, can have two if pos ANA
256
Pathyophys SLE?
Type II, III and IV hypersensitivity. ABs cf nuclear/cytoplasmic/cell membrane components.
257
Most common manifestations of SLE? Dogs? Cats
Dog - IMPA, glomerulonephritis and derm, fever
Cat - derm, fever, glomerulonephritis, IMPA. CNS more common than in dogs
258
Histopath SLE?
Interface dermatitis.
Mononuclear infiltrate at epidermal:dermal junction.
Basal keratinocyte apoptosis/vacuolar change.
Epidermal-dermal separation.
259
LE cells?
Neutrophil with phagocytosed nuclear material - SLE - spec but not sens
260
How might ANA be reported?
Titre or pattern of nuclear staining. No pattern with clinical disease severity/nature.
Low ANA in 10 % normal animals.
261
Anti histone ABs?
Histone coils DNA.
Present up to 70 % SLE.
262
SLE remission in dogs?
75 % with pred + levamisole.
ANA could corr with clin severity/improvement but might stay low pos.
263
What might you see in EMH?
More immature haematic cells - leucoerythroblastic effect.
264
Splenic nodular hyperplasia?
Lymphoid or fibrohistiocytic proliferation, latter intermediate between lymphoid and malignant splenic fibrous histiocytoma. Lymphoid may develop to haematoma in dogs (cats no as diff blood flow pattern)
265
Arginine and NO?
Need arginine for NO synthesis
266
Why are Omega 3s anti-inflamm?
Eicosapentanoic acid completes for arachidonic acid (6) for COX/LOX.
Decreased eicosanoid production.
Also PPAR gamma - decrease inflamm cytokines
267
Name some antipyretics
Steroid, neuropeptide, IL 10. Some pyrogens can be antipyretic at high temps.
268
Benefits of fever?
Improves survival and shortens length of illness.
Increase immune function ?(mobility/phagocytic ability/proliferation, NK less active though), impairment if > 41.4
269
Costs of fever?
Increase clin signs, increase metabolic rate, decrease Hb O2 affinity
270
Immunological effects of calcitriol?
Mostly anti-inflammatory - decreased TLR 4 LPS interaction, decreased TNF production
Poss immunomodulatory? Immune cells have vitamin D receptors
271
SRMA CSF sampling?
Can increase sensitivity for increased cell count if sample cervical and lumbar
272
Synovial fluid lymphocyte in IMPA?
Higher in erosive
273
Pred versus ciclosporin for IMPA?
Same response in small case numbers (70 %)
274
What is most impacted by cyclosporin - cell or humeral immunity
Cell
Decreased mast cell activity, decreased macrophage activity. Decreased intracellular adhesion molecule. inhibit APC function.
Also inh B cell AB production
275
Where is ciclosporin primarily excreted?
Bile
276
Ciclosporin P-glycoprotein interaction?
Ciclosporin substrate for and inhibitor of
277
Danger of ciclosporin and toxoplasma?
Naive infection during treatment
278
Breed for idiopathic pyogranulomatous lymphadenitis?
Springer spaniel
279
Define type I - IV IMPA
I idiopathic
II remote infectious
III GI
IV neoplasia
280
Vaccination IMPA?
One recent study found no difference
281
Relapse rate immune mediated neutropenia?
About 1/3rd in a year
282
What cytokines do cyclosporin and pred impact?
IL 2 and IFN gamma
283
Difference between SIRS criteria dogs/cats?
Cat include low HR and temp low/high cut off higher
284
How is folate absorbed?
Folate polygluconate > monogluconate (stomach deconjugation, folate deconjugase)
Folate carrier absorption
285
B12 absorption?
R protein (haptocorrin) binds after pepsin and acid liberates from animal protein, moves to IF when pH increases and with pancreatic proteases in duodenum. Cubam receptor uptake (receptor mediated endocytosis), transcobalamin II transport to liver
286
B12 storage in cats?
Rapid depletion 1-2m (rapid enterohepatic turnover). Half life 13 d healthy 5 d GI disease. No transcobalamin I (long term storage)
287
What are calprotectin, methyl histamine and brominated tyrosine?
S100A2 - calprotectin - neutrophilic inflammation marker - in faec and serum IBD
MH - marks mast cell degran - inc faec and serum IBD
BT - eosinophil activity - inc serum IBD
288
How does lateral recumbency affect video fluoroscopy?
No pharyngeal impact but decreases oesophageal transit (decreased primary peristaltic waves)
289
How would you diagnose achlorhydria?
pH > 3 increased gastrin
Also provocative testing eg pentagastrin
290
Lymphocyte ratio in feline caudal stomatitis?
CD8 >CD4
291
Breeds for oral eosinophilic granuloma complex?
CKCS, husky, malamute
292
Sialadenosis - pathophys and management?
Maybe vagus nerve abnormality? Can try phenobarbital - perhaps seizure disorder?
293
What muscles are affected in masticatory muscle myositis?
Those with 2M - masseter, temporalis, medial and lateral pterygoid. Unique myosin.
294
What pH is pepsin active at?
1.5 - 3.5
295
Is GER abnormal?
No, happens frequently in healthy dogs
296
Hyperregeneratory oesophagopathy histopath?
Spec but not sens for GERD
297
Long term omeprazole therapy?
Taper if > 2w, rebound hyperacidity
298
Most common cause of oesophageal stricture?
GER under GA. Muscular layer damaged, fibroblast .
Most common in distal oesophagus.
299
What decreases oesophageal stricture recurrence?
Triamcinolone intralesional/topical mitomycin C
300
Where do oesophageal FBs get stuck?
Points of minimal oesophageal distension - thoracic inlet, heart base, hiatus of diaphragm
301
What XR recumbency for megaoesophagus?
Left lateral best
302
Congenital megaoesophagus?
Afferent vagal innervation defect? Oesophageal motor supply defect?
Wire-haired fox terrier (auto recessive) and mini schnauzer (partial penetrance).
Various other breeds eg Irish setter, GSD, siamese
303
How many congenital megaoesophagus cases recover?
20 - 50 %
304
Most common cause acquired megaoesophagus?
Idiopathic. Vagal/muscle dysfunction? Undx MG? 26 % idiopathic cases have titre - 48 % imp with tx
305
Idiopathic megaoesophagus breeds?
Large breed middle aged
GSD Irish setter
306
What would you do if AchAR titre is in grey zone?
Repeat 4-8w esp if acute onset signs
NB in humans often neg in focal MG
307
What is the likelihood of megaoesophagus in MG responding to therapy?
50 %
308
Why would hAC cause megaoesophagus?
Impaired muscle carbohydrate metabolism/decreased muscle glycogen stores
309
How many dogs with dysautonomia have megaoesophagus?
60 %
310
Possible management options for mega-o?
Bethanecol for striated muscle, cisapride for LES
311
Negative prognostic factors mega-o?
Aspiration pneumonia
312
What might be confused for an oesophageal diverticulum in young brachycephalic dogs?
Redundant oesophageal mucosa
313
Pathophys congenital oesophageal diverticulum?
Herniation of mucosa through muscularis defect
314
How might an oesophageal diverticulum be acquired?
Pulsion or traction
315
Congenital oesophageal fistula?
Cairn terrier
316
What contrast to use if suspect oesophageal/resp comm?
Non-iodinated, iodinated osmolar/chemical pulmonary damage
317
When guarded px with oesophageal fistula?
Pleural eff, pneumonia, pulm abscess
