IMT, vWB dz, and other platelet disorders

Question 1

What are the main players involved in primary hemostasis?

Answer 1

• platelets
• von Willibrand factor
• vessel wall

Question 2

What’s the lifespan of canine platelets?

Answer 2

6-10 days

Question 3

Describe the steps in platelet activation.

Answer 3

• 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

Question 4

What are the roles of the endoperoxides prostacyclin?

Answer 4

they dampen platelet reactivity
- prostaglandin I2, prostaglandin E2, prostaglandin D2

Question 5

Which molecules play a critical role in adhesion and aggregation ?

Answer 5

integrin and non-integrin glycoprotein receptors

Question 6

What are some clinical signs of primary hemostatic disorders?

Answer 6

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

Question 7

What are some causes of secondary IMT?

Answer 7

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

Question 8

What’s the top differential for SEVERE thrombocytopenia?

Answer 8

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)

Question 9

How can platelet-bound antibody be documented?

Answer 9

flow cytometry - platelet surface-associated IgG
- sensitive, but not specific – cannot differentiate between primary and secondary IMT

Question 10

What’s the treatment for primary IMT?

Answer 10

glucocorticoids +/- cyclophosphamide (0.02mg/kg IV) – shortens recovery from around 7d to 5 d
- mycophenolate
- transfusion

Question 11

What’s the treatment for secondary IMT?

Answer 11

• removing the inciting agent/ drugs
• treat underlying disease if possible

Question 12

What’s the prognosis for primary IMT?

Answer 12

good with appropriate treatment and supportive care

Question 13

Describe feline IMT.

Answer 13

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

Question 14

What are the 3 types VWF disease?

Answer 14

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)

Question 15

How is VWF disease diagnosed?

Answer 15

• 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

Question 16

How is VWF treated?

Answer 16

• prophylaxis with oral desmopressin (it stimulates release of VWF from endothelial cells)
• blood transfusion (cryoprecipitate = best; fresh whole blood, fresh frozen plasma)

Question 17

What are some causes of acquired VWF?

Answer 17

has been reported with myxomatous mitral valve disease and subaortic stenosis

Question 18

Describe VWF disease in cats.

Answer 18

2 reported cases only
- diagnose and treat like dogs

Question 19

Define Scott’s syndrome.

Answer 19

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

Question 20

Which breed is known to have P2Y12 receptor disorder?

Answer 20

Greater Swiss Mountain Dog

Question 21

What are some causes of acquired platelet dysfunction?

Answer 21

Drugs: starch, NSAID, cephalosporins – implicated, but unclear clinical significance
Thromboembolic drugs: aspirin (irreversible cyclooxygenase inhibitor), clopidogrel (P2Y12 antagonist)

Question 22

How is platelet dysfunction diagnosed?

Answer 22

• 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

Question 23

How is platelet dysfunction treated?

Answer 23

platelet transfusion to control bleeding