IMT, vWB dz, and other platelet disorders Flashcards
What are the main players involved in primary hemostasis?
- platelets
- von Willibrand factor
- vessel wall
What’s the lifespan of canine platelets?
6-10 days
Describe the steps in platelet activation.
- endothelial injury –> platelet activation
- the binding activates granule secretion –> adenine nucleotides, Ca, serotonin, adhesive proteins (fibrinogen, VWF, fibronectin) and P-selectin
- recruits additional platelets
- forms a homeostatic plug
What are the roles of the endoperoxides prostacyclin?
they dampen platelet reactivity
- prostaglandin I2, prostaglandin E2, prostaglandin D2
Which molecules play a critical role in adhesion and aggregation ?
integrin and non-integrin glycoprotein receptors
What are some clinical signs of primary hemostatic disorders?
surface bleeding = hallmark of primary hemostatic disorder
- petechia, ecchymoses, epistaxis
- VWD rarely have petechia, ecchymoses may be possible after trauma/ surgery
- cavity bleeding possible, though more common with secondary hemostatic disorder
What are some causes of secondary IMT?
Drugs: cephalosporins, sulfonamides; any drugs can
Infectious agents: Anaplasma, Ehrlichia, Babesia, Leptospirosis, Leishmania
Neoplasia: increased platelet consumption secondary to bleeding, decreased production
IMT noted with lymphoma, HSA, histiocytic sarcoma
What’s the top differential for SEVERE thrombocytopenia?
primary IMT
- though IMT is not as common as secondary IMT, it’s most likely to cause severe thrombocytopenia (<30K, positively correlated with spontaneous bleeding)
How can platelet-bound antibody be documented?
flow cytometry - platelet surface-associated IgG
- sensitive, but not specific – cannot differentiate between primary and secondary IMT
What’s the treatment for primary IMT?
glucocorticoids +/- cyclophosphamide (0.02mg/kg IV) – shortens recovery from around 7d to 5 d
- mycophenolate
- transfusion
What’s the treatment for secondary IMT?
- removing the inciting agent/ drugs
- treat underlying disease if possible
What’s the prognosis for primary IMT?
good with appropriate treatment and supportive care
Describe feline IMT.
Rare
- similar presentation as dogs
- mortality rate 15%
- oral prednisolone only effective 5/9 cats
- immunosuppressants/ chemo have been tried but not enough to comment on efficacy
What are the 3 types VWF disease?
Type 1: low numbers of VWF, but all arrays are present (mild to moderate bleeding tendency)
Type 2: variable deficiency in VWF, but the high molecular weight is absent (moderate to severe bleeding tendency)
Type 3: no VWF (severe bleeding tendency)
How is VWF disease diagnosed?
- buccal mucosal bleeding time (>4min + thrombocytes >100k + PCV > 30% = positive for VWF disease)
- excessive bleeding after Sx or trauma
- PT, PTT = normal
- quantitative assay available in Cornell, but can be interfered with inflammation or pregnancy
- DNA testing: type 2 and 3 = autosomal recessive
- use DNA testing to detect carriers
- type 2 VWF disease will require qualitative assay – ELISA test available
How is VWF treated?
- prophylaxis with oral desmopressin (it stimulates release of VWF from endothelial cells)
- blood transfusion (cryoprecipitate = best; fresh whole blood, fresh frozen plasma)
What are some causes of acquired VWF?
has been reported with myxomatous mitral valve disease and subaortic stenosis
Describe VWF disease in cats.
2 reported cases only
- diagnose and treat like dogs
Define Scott’s syndrome.
This is hereditary defect in platelets – can’t externalize PS –> cannot form proper scaffolding with prothrombinase etc
- lack of platelet procoagulant activity (PCA) –> insufficient thrombin generation to support fibrin clot maturation and stabilization
only found in German Shepherds
- no ecchymosis or petechia
- epistaxis, excessive post-surgical bleeding, soft tissue hemorrhage
- all screening tests: BMBT, PT, PTT, TEG, PFA-100, platelet aggregometry = normal
- do flow cytometry or DNA testing
Which breed is known to have P2Y12 receptor disorder?
Greater Swiss Mountain Dog
What are some causes of acquired platelet dysfunction?
Drugs: starch, NSAID, cephalosporins – implicated, but unclear clinical significance
Thromboembolic drugs: aspirin (irreversible cyclooxygenase inhibitor), clopidogrel (P2Y12 antagonist)
How is platelet dysfunction diagnosed?
- spontaneous bleeding –> petechia, ecchymosis, mucosal surface bleeding
- excessive bleeding following Sx, or trauma
- normal platelet count, PT, PTT, and plasma VWF:Ag concentration
- BMBT test and PFA-100 = good screening tests
- DNA testing for susceptible breeds
How is platelet dysfunction treated?
platelet transfusion to control bleeding
