Haematology and Immunology: Clinical COPY Flashcards
What type of immune response is immune mediated disease generally caused by?
TH2 responses (antibodies against a self antigen)
What percentage of dogs will have bacteria when on immunosuppressive treatment?
30%
Why is PT often prolonged first in disorders of coagulation?
Factor VII from the extrinsic pathway has the shortest half life of all the factors so is often consumed first.
Prothrombin time:
- Test characteristics
- What it tests
- Point at which the test is considered complete
- Plasma is added to a medium containing calcium chloride and tissue factor within a lipid membrane.
- Tests the extrinsic and final common pathway
- The PT finishes when fibrin strands form
aPTT
- Test characteristics
- What it tests, what it does not test
- Plasma is incubated with a contact activator (e.g. kaolin, celite) which will activate XII and the pathway continues.
- Tests the intrinsic pathway and final common pathway.
- The fibrin stabilising complex (XIII) and the extrinsic pathway (VII) are not tested.
What Ddx could you have for:
- Increased PT but normal aPTT?
- normal PT but increased aPTT?
- Early rodenticide toxicity
- Factor XII (Hageman) deficiency, Factor XI (haemophilia C), Factor IX (Haemophilia B) or Factor VIII (Haemophilia A), heparin therapy.
ACT
- Test characteristics
Whole blood is used and a contact activator is added. The platelets acts as their own membrane for the tests. Therefore, visible clot formation is the end point.
How is fibrinogen measured?
The Clauss method: fibrinogen is exposed to a large amount of thrombin.
Reasons for reduced fibrinogen concentrations
Anticoagulant use
Elevated FDPs
Decreased albumin
XIII deficiency (as the fibrin is not stabilised)
Amyloidosis
How is thrombin clot time measured?
By adding lots of thrombin to citrated plasma. It is measuring the function/levels of fibrinogen.
What is FDP measurement testing and what are some Ddx if this is normal?
FDPs are produced when plasmin lyses fibrin clots. Therefore, elevations may occur in:
- DIC
- Rodenticide toxicity
- Hepatic disease
- Thrombotic diseases
What are D-dimers?
These are specific FDPs that are only produced from cross-linked fibrin. They have a very short T1/2 so can indicate recent fibrinolysis.
TEG parameters and alterations with hyper and hypocoaguable states.
R = the time to onset of fibrin formation
K = time for the deviation of the needle by 20mm (this is a measure of speed of clot formation)
alpha angle = speed of clot formation
MA = maximum strength of the clot
The LA30 and LA60 = the amount (%) of clot that has undergone lysis by 30 minutes and 60 minutes, respectively.
Which TEG parameters indicate:
- Coagulation factors
- Platelet number and function
- This is generally indicated by the reaction time (time to fibrin formation)
- This is indicated more by the rate of fibrin formation (e.g. alpha angle, k etc.)
How much of a reduction in clotting factor activity is required before PT/aPTT are prolonged?
50-70%
What will the following alterations result in on TEG testing?
a) low PCV
b) Increased fibrinogen
c) Thrombocytopenia
a) + b) will appear hypercoaguable
c) will appear hypocoaguable
What percentage of mortality in IMHA is likely due to thromboembolic disease?
up to 50%
What is the incidence and survival of ATE in cats with cardiac disease?
33% incidence and 35% survival
What percentage of dogs with PLN will suffer thromboembolic complications?
14-27%
What is the most common cause of pulmonary thromboembolism in dogs?
Neoplasia
In what neoplasias is DIC a common problem?
Haemangiosarcoma
Mammary carcinoma
Pulmonary adenocarcinoma
How long does it typically take for clinical bleeding to occur following rodenticide toxicity?
2-5 days
What are PIVKAs
Proteins induced by vitamin K abscence. This test will be prolonged if vitamin K is deficient in some way.
Which factor is increased in DIC and is thought to be a major contributor to its development?
Increased expression of tissue factor.
The extrinsic pathway is then activated and there is consumption of coagulation factors. Therefore, there are two phases:
- Compensated = hypercoaguable
- Uncompensated = bleeding
What are the diagnostic criteria for DIC?
n.b. there may be some actual criteria here but this is what I have noted from Ettinger
PT/aPTT alterations
Thrombocytopenia
Increased FDPs/D-dimers
Hypofibrinogenaemia
Decreased antithrombin
Treatment of DIC
Compensated phase = anticoagulants
Uncompensated = FFP transfusion
What are acquired anti-coagulants?
Spontaneous development of antibodies to a coagulation factor, anti-phospholipid antibodies (lupus anticoagulant) is another type.
How are acquired anti-coagulants tested for?
By the ‘plasma mixing test’ which is where patient and control plasma is mixed. Coags would remain prolonged following mixing due to the presence of antibody in the patients plasma.
Which clotting factors are contained in the following blood products:
- FFP
- Cryoprecipitate
- Cryosupernatent
- Stored plasma
- FFP = contains all the factors
- Cryoprecipitate is primarily VIII, XIII, vWF, fibrinogen and fibronectin (less than FFP but small volume required)
- Sufficient coagulation factors other than those in cryoprecipitate
- Lowe levels of V and VIII but has adequate VitK dependent factors.
Which blood products should be used for rodenticide toxicity?
FFP or stored plasma are best for this.
Pathophysiologic and genetic basis for Scott syndrome
Diagnosis
Deficient procoagulant activity (phosphatidylserine) on the platelet surface.
Autosomal recessive trait of GSD
Diagnosis:
- Prothrombin consumption assay
- Flow cytometry for the PTS on the platelet surface
What breed of cat has vitamin K gamma-glutamyl carboxylase deficiency been documented in?
Devon-Rex
Which factors are deficient in the following diseases?
- Haemophilia C
- Haemophilia A
- Haemophilia B
- Stuart-powell deficiency
- Christmas disease
C = XI
B = IX (aka. christmas disesase)
A = VIII
- X
What is the mode of inheritance of haemophilia A & B?
Autosomal X-linked recessive.
What factor can potentially be increased with desmopressin therapy?
Factor VIII is increased in people but not dogs.
If haemorrhage is suspected in a cat with Hageman’s trait, what should be evaluated for next?
A concurrent haemophilia as Hageman trait should not result in clinical bleeding.
Why might Rts be falsely increased soon after haemorrhage?
Due to release from bone marrow storage pools
How is the OFT performed and interpreted?
Two tubes with RBCs (0.9% saline and 0.55% saline) are incubated and centrifuged for 5 minutes
If 0.55% is haemolysed to a greater degree this indicates increased fragility.
Why does hypophosphataemia result in haemolytic anaemia?
It reduced RBC ATP stores which will then destabilise the membrane.
In which Babesia species infection do anti-RBC antibodies develop?
B. gibsoni and B. vogeli
Which markers may differentiate histiocytic proliferation from haemophagocytic histiosarcomas?
CD11/CD18
Which breeds are predisposed to haemophagocytic HS
Golden Retriever, Bernese Mountain Dog, Golden Retriever, Flat-Coat
What are the major targets of Ig binding in IMHA?
Anion-exxhange molecule, erythrocyte membrane glycoproteins
What are the poor prognostic indicators for canine IMHA?
- Icterus
- Petechiation
- Increased urea
- Increased aPTT
- Thrombocytopenia
- Left shift and monocytosis
- Increasing cytokines
What is the pathomechanism of feline alloimmune haemolysis?
Type B cats develop type A autoantibodies in the first few weeks of life.
Therefore, if a type B cat has A or AB kittens their antibodies are passed on in the colostrum.
(Also explains why you should never give a type A cat type B blood)
Which reticulocytes are counted by haematology analysers?
Aggregate
Normal lifespan of canine and feline RBCs
100 days, 72 days
factors known to reduce EPO production
Renal disease
PTH
Low albumin
Ferritin and transferritin
Hormones known to facilitate EPO release/production
ACTH
Cortisol
ANG II
TSH and thyroxine
Cells that produce EPO
Peritubular interstitial cells of inner cortex and outer bmedulla
Which IL is responsible for increased hepcidin production?
IL-6
Reason for anaemia in copper deficiency?
Copper is required for haemoglobin synthesis but is an uncommon cause of anaemia in veterinary species
What is the expected EPO level in primary polycythemia (polycythemia vera)?
Should be low due to negative feedback mechanisms.
What treatment stragies are there for polycythemia vera?
Hydroyxurea
Chlorambucil
Radiophosphorus treatment
What is the lifespan of platelets in circulation?
6-10 days
What is the role of vWF in clotting?
vWF binds to exposed subendothelial collage and facilitates PLT binding through GP1b/V/IX
Conformational changes then expose the GPIIb/IIIa receptor, vWF binds here to allow plalet aggregation and binding with fibrinogen.
Which drugs has IMTP been more often associated with (compared to others)
Cephalosporins and sulfonamides
How can anti-platelet antibody be tested?
Through flow cytometric techniques.
How much quicker (approximately) are vincristine treated dogs likely to have
approx 2 days
Which second agent monotherapy does ettinger cite as being effective for treatment of IMTP?
Mycofenolate mofetil
Is there a benefit to the use of lyphophylised canine platelets in IMTP?
Not shown to be of benefit in a prospective study.
How do plasma vWF levels, vWF multimers and bleeding risk vary with vWB types?
To what degree of platelet reduction and anaemia can a BMBT be performed without concern for an impact on results?
PLT > 1000x10e9/L and PCV >30%
In which type of vWD might PFA be appropriate?
Type 1
In which type of vWD is the vWF quantification (vWF:Ag) assay not going to be beneficial?
Type 2 since vWF can be normal in this type.
Which vWD type is the qualitative assay used in?
Type 2, this is the case as a functional assay is required to demonstrate that the multimers are not present.
The factor binding to collaen is compared to the amount of VWF (vWF antigen). If this ratio is high then this is consistent with T2 vWD.
What are the treatment options for vWD?
Desmopressin
FFP or cryoprecipitate (the latter may be preferred due to needing less volume)
In what cases has acquired vWF deficiency been documented in dogs?
MMVD
Tetrastarch administration
Angiostronglus
What breed has P2Y12 disorder been documented in?
Greater Swiss Mountain Dogs
Ciclosporin MoA
Inhibition of calcineurin which results in the inability to phosphorylate NFAT therefore reducing cytokine production, particularly IL2 (also 3, 4, TNFa)
Azathioprine MoA
Thiopurine (purine analogue = adenine, guanine).
Mycofenolate mofetil MoA
Also a purine analogue but inhibits inosine monophosphate dehydrogenase (IMPDH) which is required for de novo purine synthesis
Leflunomide MoA
Pyrimidine synthesis inhibitor (inhibits dihydro-orotate dehydrogenase which is a de-novo synthesis of pyrimidines inhibitor)
Chlorambucil MoA
Alklating agent – DNA cross-linking
hIVIG MoA
Binds to the Fcg receptors on macrophages which prevents them taking up opsonised components.
How are the polyarthritides classified?
Which rickettsial diseases can cause a polyarthritis?
Borrelia
Ehrlichia
Anaplasma
Ricketsia ricketsii
What scenario might promt you to look for a bacterial L-form arthritis?
If you have cutaneous abscessation or draining tracts.
What neoplasia’s have reactive polyarthropathies been reported in?
Carcinomas
Seminomas
Sertoli cell tumours
Leiomyomas
What is the most common manifestation of SLE in dogs vs. cats?
Dogs: Polyarthropathy
Cats: dermatological and CNS signs
Which breed, other than the Shar-Pei, has a breed associated non-erosive polyarthritis been described in?
Akita
What percentage of dogs with IMPA have pyrexia?
50%
How many joints does Ettinger suggest tapping to make a diagnosis of IMPA?
>/= 4
What is rheumatoid factor?
It is a collection of autoantibodies that form against IgG (Fc region) and their normal role is to facilitate their clearance through opsonisation.
What are the diagnostic criteria of SLE in veterinary medicine?
The presence of 2 or more signs of autoimmunity along with the presence of ANA antibodies.
or
The presence of 3 or more signs of autoimmunity with or without ANA antibodies
Breed(s) predisposed to having a large spleen
GSD
Breed(s) predisposed to having a caudal spleen
Miniature schnauzer
Cocker spaniels
Greyhounds
What is the characteristic appearance of splenic torsion on abdominal ultrasound?
Swiss cheese appearance
Which sedative/anaesthetic drug does not tend to cause splenic enlargement?
Propofol
What is the pathomechanism behind X-SCID?
A mutation in the gamma chain of IL-2 resulting in a T-lymphocyte deficiency in affected breeds (Welsh Corgi and Basset hound)
Lipaemia effect on TP measurement?
Will increase TP measurement with refractometer reading, but will not effect machine measured TP.
