Arterial Thromboembolism

Question 1

What’s virchows triangle?

Answer 1

1. Endothelial damage
2. Blood stasis
3. Hyper coagulable state

Question 2

Which hormone contributes to the lack of collateral blood supply?

Answer 2

Serotonin

Question 3

What are the clinicians signs of saddle thrombus?

Answer 3

Ischemic neuromyopathy

Question 4

What’s the 2nd most common place for ATE in cats with heart disease?

Answer 4

R subclavian artery

Question 5

Where does the serotonin and theomboxane come from?

Answer 5

Platelets

Question 6

How is collateral blood supplied improved?

Answer 6

Clopidogrel: helps with vasodilation (reduces the effects of vasoconstriction)

• anti-thromboxane in cats
• anti- serotonin in cats
• good vasodilation

Aspirin- effective anti-serotonin in cats but need dose high enough that can cause toxicity

Question 7

What other clinical signs can be noted based on different underlying conditions?

Answer 7

• generalized
• IMHA
• nephrotic syndrome
• Cushing’s
• heart disease

Question 8

What are the treatment goals for ATE?

Answer 8

1. Reduce thrombus formation
2. Improve collateral blood supply
3. Pain management
4. Addressing underlying condition
5. Supportive therapy

Question 9

What can be used to reduce thrombi formation?

Answer 9

1. Unfractionated heparin
   - deactivates IIa, Xa, XIa, XIIa, also V & XIII
   - can deactivate platelet function as well
   - watch for thrombocytopenia
   - should do baseline PT, PTT, TEG
2. Low molecular weight heparin is another option but less studied

Question 10

What’s the likelihood of reperfusion injury in cats?

Answer 10

• 40-70%
• the risk of mortality is up to 40%
• not all ATE need thrombolytic treatment
• but its very important for cerebral, renal and splenic infarcts

Question 11

Which drugs can be used to dissolve thrombus?

Answer 11

1. Streptokinase
   - forms complex with plasminogen to deactivate plasminogen, plasmin, fibrin, fibrinogen, and coagulation factors
   - repeated dosing leads to antigenic stimulation
   - not available in the states
   - one study had high mortality rate in cats
2. Urokinase
   - more specific plasmin activator than streptokinase (goes to the thrombus rather than circulation as well)
   - high mortality in dogs in one study (100%)
   - also not available in the states
3. Tissue plasminogen activator
   - also more thrombus specific
   - at high dose can lead to systemic effects and bleeding
   - ok efficacy
   - only one approved for human use on the states

Question 12

What are some options for pain managemnet?

Answer 12

Opioids!
- buprenorphine
- hydromorphone
- fentanyl

Question 13

What’s the survival of ATE in cats related to CE?

Answer 13

• there is no difference between conservative vs thrombolytic therapy (35-39%, vs 33%) for survival
• cause of death is similar for treatment vs euthanasia (28-40% natural vs 25-35% euth)
• prognosis is better for single pelvic (68-93%) vs bilateral pelvic (15-36%)
• long term survival after initial CE ranged from 50-345 days

Question 14

How is ATE prevented in cats?

Answer 14

Primary preventions:
- cats with echo evidence of left atrial enlargement: L atrium > 1.7cm in diameter or the La/Aorta ratio is >2.

Secondary preventions:
- to prevent more ATE in the future –> clopidogrel
- 1 year recurrence rate (general) 25-50%

Question 15

What is the goal of ATE prevention?

Answer 15

For patients with underlying disease such as heart disease or nephrotic syndrome, complete prevention of ATE is unrealistic.
Goal should be to prolong the time to the next ATE or to reduce the severity/ minimize the clinical signs

Question 16

What are some anti-platelet agents used for prevention of ATE?

Answer 16

1. aspirin
2. clopidogrel

Question 17

How does Aspirin work?

Answer 17

It’s the anti-thromboxane
- irreversibly acetylates platelet cyclo-oxygenase, preventing the formation of thromboxane A2
- Thromboxane A2 = potent pro-aggregation and vasoconstrictive properties
- aspirin prevents secondary platelet aggregation
- use in cats = watch for GI signs, low dose no less effective but less side effects. Recurrence rate = 17-75%
- less well established in dogs

Question 18

How does clopidogrel work?

Answer 18

• it’s a potent and irreversible antagonist of ADP receptor
• inhibits both primary and secondary platelet activation
• the conformational change of the ADP complex inhibits binding of fibrinogen and von Willebrand factor
• also impairs platelet release reaction, decreasing the release of pro-aggregating and vasoconstrictive agents
• requires hepatic metabolism to be active
• no GI toxicity in cats
• very bitter

Question 19

What are some anti-coagulants that can be used to prevent ATE?

Answer 19

1. Warfarin
2. low molecular weight heparin
3. new anticoagulants (not as well studied right now, but not inferior to warfarin)

Question 20

How does warfarin work?

Answer 20

• it antagonizes vitamin K dependent coagulation factors: II, VII, IX, X, as well as anti-coagulant proteins C & S
• so initially will be hypercoagulable (with inhibition of protein C), so administer heparin at the same time
• bleeding is possible
• needs dedication on monitoring and $
• recurrence rate in cats 42-53%
• bleeding risk 13-20%, 13% = fatal

Question 21

How does low molecular weight heparin work as a preventative for ATE?

Answer 21

• it inhibits Xa, and not much IIa, so checking the PTT or TEG is not helpful –> need to monitor Xa levels
• comparable results with warfarin in cats with ATE due to heart issues
• but no bleeding noted