Immune Mediated Disease Literature Flashcards
In healthy SCWT, what has been noted to be increased in animals that have siblings with PLE/PLN?
• High prevalence of perinulcear antineutrophilic cytoplasmic autoantibodies (pANCA) in healthy Wheatens (21%)
○ Significantly association of + pANCA and diagnosis of PLE or PLN in sibling
Did immunosupression have an effect on Coomb’s?
NO!
Did storage have an effect on Coomb’s?
NO! Samples were stored chilled for up to one week!!!
Did blood transfusion have an effect on Coomb’s
NO! Did NOT result in a false + result
What is a sensitive and specific test for IMHA that is resilient to storage, immunosuppression, and transfusion artifacts?
Coomb’s (DAT - Direct Antiglobulin Test)
Sn: 50-89%
How often can blood donors donate blood?
• Donors >27 kg can donate 450 mls (16 ml/kg) every 3 weeks without experiencing adverse effects
How long can you store fresh whole blood and have the platelets still work?
About 72 hrs
Just don’t chill = KILLS platelets
If you give 10 ml/kg of fresh whole blood, how much will this increased your platelet count?
About 10K
If you give 1 unit of platelet rich plasma, how much will this increase your platelet count?
Max 40K
What happens to thrombocytopenia patient’s vessels over time?
Platelets are important for plugging gaps in endothelium - over time thrombocytopenic patients get “gaps” / thinning in their vessels
What did feline idiopathic pure red cell aplasia respond to?
Steroids and cyclosporine
MST: 31-406 d
Relapse common
But 4 cats went into remission
What composes IVIg?
90% biologically intact IgG (little IgA, IgM, CD4, CD8, human leukocyte antigen)
T1/2: Dogs 7-9 days
What is the MOA of IVIg?
○ Blocks Fc receptors, eliminates pathogenic autoantibodies, modulate cytokine synthesis, inhibit complement, mediate Fas-Fas ligand interactions
What are the uses of IVIg in vet med?
§ Use in vet med: IMHA, ITP, pemphigus foliaceus, SARDS, myasthenia gravis, cutaneous disease
What are adverse events with IVIg?
Type I hypersensitivity/anaphylaxis; hypercoagulation (TED), renal failure, hypotension, pseudohyponatremia
What had an effect on the plasma concentrations of prednisolone in healthy dogs?
• Modulation of P-glycoprotein expression influenced plasma concentrations of prednisolone PO (healthy beagles)
○ Rifampicin (induce P-gp) - Upregulated duodenal P-gp in dogs and reduced AOC of pred
○ Ketoconazole (inhibitor of P-gp) - Downregulated expression of duodenal P-gp and increased AOC of pred
What could be used to monitor immunosupression with cyclosporine?
Flow cytometery: • Direct T cell function (flow for IL-2, IL-4, IFN-gamma) may be effective/more sensitive to monitor immunosupprressive tx with cyclosporine in dogs
○ Low dose (5 mg/kg PO q24hrs): Significant decrease in IFN-gamma but IL_2 was unaffected
○ High dose (10 mg/kg PO q12hrs): Significantly decreased IL-2 and IFN-gamma, but NOT IL-4
○ T-cell function is suppressed at trough blood concentrations >600 ng/ml, at least partial suppression at lower doses
What effects do high doses of methylprednsiolone have on neutrophils?
• High doses of methylprednisolone (MPSS) suppressed major functions of neutrophils (including adhesion markers CD11b, CD18; decreased phagocytosis; reduction in oxidative burst) for at least 7 days after tx
No significant change in migration noted
Is transdermal cyclosporine recommended in cats?
NO! Inconsistent absorption
For IMHA patients, what is superior: aspirin. plavix, or both?
No difference in survival btwn groups in survival = All about 13% mortality and TED about 13%
For IMHA patients, what is superior: constant dose heparin or individually dosed heparin?
% mortality and incidence of TED significantly different btwn groups
MST: Constant heparin 68d vs individual dosed heparin >180 d
For IMHA patients, was plasma helpful for preventing TED?
No difference btwn groups (all dogs were on heparin too)
Why should we not call it “Evan’s syndrome”?
Since we cannot rule out IM process, bystander effect, vs onset of DIC
Which is better for IMHA, azathiaprine, cyclosporine, or cyclophosamide?
No evidence of azathiaprine vs cyclosporine
DO NOT use cyclophosamide
Did IVIg result in improved survival in IMHA dogs?
NO! But it did improve hematologic parameters
What antithrombotics were associated with improved survival in IMHA?
Individually dosed heparin and low dose aspirin
What are the major prognostic indicators in IMHA dogs?
Bilirubin and BUN (>56)
Others: □ Spherocytosis □ Sex (male) □ Season (warm) □ PCV (0.23 mg/dl □ Monocytes >100/ul □ aPTT □ IL-18
MCP-1
Is there a seasonality to IMHA?
Yes
Reported: ○ More cases in spring and summer at the San Diego office NOT true for LA practice
Can mycophenolate be used for IMHA?
Yes! - Reported in dogs and cats
• Mycophenolate in dogs with IMHA did result in remission BUT also horrible GI -toxicity (10-15 mg/kg PO q8hrs, HIGH DOSE)
○ In combination with pred and low dose aspirin (20.5 mg/kg/day)
What has been shown with using lactate in IMHA patients regrading prognosis?
lactate concentration at presentation was significantly higher in nonsurvivors than survivors
○ Serial lactate was a better measure (more predictive), If persistent hyperlactemia at 6 hours after admission they were less likely to survive
§ Optimal lactate cut off 4.4 mol/l (correctly predicting outcome 73%, sen 60%, spec 77%)
§ All dogs with lactate that normalized within 6 hrs survived, only 71% with high lactate at 6 hrs survived
Overall survival: 77%, 20% euthanized, 3% died
What is the prognosis of IMHA when there is severe thrombocytopenia (
○ Similar survival to either disease alone (75% survived and 25% euthanized)
○ Younger dogs were more likely to survive
What should pANCA not be used as a biomarker of IBD?
• Perinuclear antineutrophilic cytoplasmic autoantibodies (pANCA) were detected in a IMHA dogs (47%) and dogs with vector borne disease (48% esp if titer for Leishmania infantum), and 5% in healthy dogs
○ pANCA is a non-specific marker and should NOT be used for IBD
○ May be a biomarker of IM or infectious diseases
Based on TEG what do IMHA look like?
Hypercoag!! Even before pred given
What has been associated with more severe more severe degree of anemia, spheocytosis, and autoagluttination in IMHA dogs?
• Dogs with IMHA with ≥ 2 Ig isotype bound to RBCs (IgG and IgM) are likley to have more severe degree of anemia, spheocytosis, and autoagluttination
○ Lower HCT if IgG AND IgM compared to only one isotype
More spherocytes if IgG AND IgM compared to only IgM
Have IgA antibodies been reported in dogs with IMHA?
YES! One case
What is true regarding the cytokine profile in IMHA dogs?
• Mixed cytokine response in IMHA dogs: Marcophage/moncyte activation and recruitment increased in nonsurvivors (IL-15, Il-18, GM-CSF, MCP-1)
○ Increased Il-18 and MCP-1 were independently associated with mortality (prognostic indictors)
Which cytokines when elevated have been related to a poor prognosis with IMHA?
Increased Il-18 and MCP-1
What is true regarding platelets in IMHA patients?
• Dogs with IMHA have increased platelet activation (based on flow cytometry) - Even more activated if thrombocytopenia noted with IMHA
Which spp with IMHA is more like to have persistent cold autoagglutination and Coomb’s + at 37C with polyvalent antiserum?
CATS wth IMHA
What combination has been shown in dogs to improve outcome with IMHA?
Steroids, azathioprine, and ultra-low dose aspirin (Weinkle study)
What are microparticles?
• Membrane derived from many cell types that are released into circulation
○ Budding of phospholipids secondary to disruption of phospholipids
○ Can express antigen, cell surface proteins, cytoplasmic content, and nuclear components
Release can be physiologic or pathogenic
What makes microparticles proinflammatory and procoagulant?
Active phospholipids on outer leaflet
How did lyophilized platelets compare to fresh platelet concentrate in bleeding ITP dogs?
no difference in transfusions needed, hospital time, survival to d/c or 28 days
○ Very small sample size!!! But low adverse reactions
What are the two big prognostic factors in dogs with ITP?
Melena and high BUN
In dogs with ITP what was related to needing more tranfusions?
Melena
What can be monitored in dogs with ITP that changes prior to plt count?
PCT may be used to monitor ITP dogs
○ Time to achieve PCT (estimate of platelet mass, threhold = 0.07575) was shorter than for seeing platelet count (threhold 75k) (3 vs 4 days)
ITP dogs had increased MPV compared to controls
How did IVIg compare to vincristine in ITP Dogs?
No difference btwn groups at discharge, 6 months, or 1 year
○ Median platelet recovery time: 2.5 days
What was the mean platelet recovery time for IVIg and vincritsine in dogs with ITP?
○ Median platelet recovery time: 2.5 days
§ Previous studies (IVIg 3.5 days and vincristine 4.5 days)
What is recommended IVIg or vincirstine for ITP dogs?
No difference btwn groups at discharge, 6 months, or 1 year
○ Median platelet recovery time: 2.5 days
○ Cost of tx higher in IvIg group ($4100) compared to vincristine ($2400)
§ Since vincristine is CHEAPER they are recommending this over IVIg
Within 42 days is there an association of ITP with vaccination?
NO!
• No association btwn idiopathic ITP and recent vaccination (within 42 days)
○ ITP (48) 8 % vs controls (96, age matched) 14%
Which drug has been used as a sole agent in ITP dogs and has resulted in complete remission?
Mycophenlate
What in IMPA dogs has been correlated with median pain score, joint cellularity, and mobility (accelerometry)?
• C-reactive protein higher in IMPA dogs (>75 ug/ml) compared to controls Might be able to use for monitoring, instead of joint taps
○ Significantly lower at 2 weeks and even lower at 4 weeks of tx
○ Correlated with median pain score, joint cellularity, and mobility (accelerometry)
○ Normal CRP in dogs with OA
Which cytokines did not correlated well with CS, joint cellularity for IMPA dogs?
§ Plasma IL-6 higher in IMPA dogs compared to controls
□ Lower at week 4 of tx but only modest correlation with pain scores
CXCL8 (IL-8) did NOT differ btwn IMPA and healthy dogs
What immunosuppressive has been evaluated in dogs with IMPA and how did it do?
• Lefluonmide (3-4 mg/kg PO q24hrs) was used to tx IMPA in dogs, recommend tx for 6 weeks prior to changing
○ Changes based on cytologic joint eval and CS
○ 8/14 complete remission, 5 partial remission, 1 minimal response
What is seen in sled dogs after racing in regards to Ig?
• Sled dogs racing long distance had a substantial decrease in [IgG] (training and racing) and IgM and IgE - Hypogammaglobulinemia after racing (32% dogs)
○ Compared to 18% before race and 24% 4 months after race
What is the reading on a serum protein electrophoresis called?
Densitometer
In cats with serum protein electrophoresis performed, what is the most common finding?
Polyclonal gamma globulins = Most related to infectious causes
39/80 dx with FIP!!!
What is a potentially rare adverse fatal complication of phenobarbitol?
Dysmyelopoiesis
What are the common bloodwork changes with starvation?
Hypoalbuminemia, thrombocytosis, anemia, increased BUN, elevated BUN/crt ratio, and hypocalcemia
○ Dogs with anemia and hypoalbuminemia may need more time to gain weight
In the Wachtehund, what def is noted and what are CS?
• Phosphofructokinase deficiency seen in Wachtelhund (exercise intolerance, hemolytic anemia, pigmenturia)
NOT same mutation (muscle type PFK M-PFK gene) as in Springers, Cockers, Whippets, Mixed breeds
What is congenital methemoglobinemia and how is it tx?
• Congenital methemoglobinemia in dog dt cyctochrome B5
Treated with methylene blue
In dogs with regenerative anemia is macrocytic hypochromic that most common finding?
NO!!! Moderate accuracy 70%
What is a the best predictor of regenerative anemia in dogs?
○ Polychromasia +/- high RDW were more accurate (77% poly only and 79% poly + high RDW)
Compared to High MCV and Low MCHC = Moderate accuracy for detecting regeneration (70%, sen 11, spec 98)
Is regenerative or nonregenerative anemia more common in cats?
Anemia in cats (1,098): Most were nonregenerative (58%) vs 43% for regenerative
Can you use the RBC indices to detect regeneration in cats?
NO! ○ Erythrocyte indices were NOT sensitive for regeneration (high MCV/low MCHC: Sen 20%, spec 91%)
In cats, is the severity of the anemia associated with prognosis?
NO! BUT, was with etiology of anemia and classification of disease
§ More likely to survive if hemolysis (than BM dz) and IM dz (than neoplasia)
What is true regarding cats with degenerative left shifts?
1.57X more likely to die or be euthanized in hospital than cats w/o degenerative left shift
○ Increasing severity of left shift is associated with increased likelihood of death or euthanasia
○ Over 20 days after admission
○ Also FeLV infected cats were >3 fold higher hazard of death/euthanasia compared to noninfected cats
○ Purebreeds lower risk of death
What is true regarding dogs with degenerative left shifts?
significant predictor (2 fold) of death or euthanasia but it was related to disease state and should be used with caution
○ Age also strong predictor
○ Did NOT detect a trend in severity of left shift and hazard of death/euthanasia
Were increasing severity of degenerative left shift associated with hazard of death in dogs and cats?
In cats YES
In dogs NO!
What is a better method of DEA 1.1 typing in patients with IMHA?
○ Errors in patients with IMHA
§ Immunochromatographic cartridge may be better for typing animals with agglutination present
Which disease in cats results in discordant blood typing?
FeLV
Does hyperbilirubemia result in changes in total protein obtained by refractometry?
NO!
Did NOT interfere with refractometric estimate of total protein (up to 41.5mg/dl bilirubin)
○ Some variation with total proteins related to method of conversion of refractive index to total protein concentration, NOT bilirubin concentration!
Can sedation in cats affect CBC and chem results?
YES! But not that are clinical relevant
In ill cats, what is a common finding on chemistry that is related to longer hospital stays, more cost, and higher mortality? Can it be used to predict outcome in cats?
CK
• Increased CK (creatine kinase) is very common in ill cats (60% samples): Cats with increased CK longer hospitalization, more expensive costs and high mortality
○ BUT CK was inaccurate outcome predictor in cats
What is Scott Syndrome?
• GSD with hemorrhage consider canine Scott Syndrome (platelet procoagulant deficiency)
○ No petechia noted
○ Most responded to platelet transfusion
When can you see a contraction alkaloids?
Dt fluid loss = Volume contraction (esp if from vomiting)
Do sled dogs have iron def after racing?
Unlikely only 4% had low ferritin
BUT detection of it was inhibited by presence of inflammation (high ceruloplasmin and CRP)
What are risk factors of peri-op death for dogs with splenic masses?
• Marked pre-op thrombocytopenia, anemia, and intra-op ventricular arrhythmias were RISK factors for pei-op death in dogs with splenic masses
○ 8% died: Thrombotic or coagulatopathic syndromes, bleeding mets
○ Every 10K decrease in platelets = Increased odds of death by 6%
○ OCV 30%
○ Intra-op arrhythmias odds of death twice those that did not have arrhythmias
What infectious disease has been isolated from splenic masses?
Bartonella DNA higher prevalence in fibrohistiocytic nodules (30%) and HAS (26%) in dogs compared to lymphoid nodular hyperplasia (10%) and controls (0%)
○ Babesia and hemotrophic Mycoplasma DNA were significantly lower than Bartonella
○ No difference in 3 infectious dz and lymphoid nodular hyperplasia
What can a higher mean mass to spleen volume ratio AND higher splenic weights as % body tell you about splenic masses in dogs?
• Dogs with benign splenic masses significantly higher mean mass to spleen volume ratio AND higher splenic weights as % body than dogs with HSA
