QUESTIONS

1. Which type of cardiomyopathy seems to involve the highest predisposition for saddle thrombus?
    
2. If a cat with a saddle thrombus is going to regain function of the rear legs, how long can this be expected to take?
    
3. In cats treated with aspirin for prevention of future episodes what can one expect?
    
4. Aspirin works by inhibiting what enzyme?
   
   This inhibition is (choose one) reversible/irreversible.
    
5. Why is heparin recommended for treatment if the thrombus has already occured?
    
6. What M-mode findings are felt to be predictive of an episode of thromboembolism?
    
7. What kind of recurrence rate is being found for cats on warfarin therapy?
    
8. Why can't the syndrome be re-created by just ligating the aorta?
    
9. In warfarin therapy, what is the significance of the terms INR & ISI?
    
10. A vasodilator is recommended for treatment of the saddle thrombus episode.  Why might hydralazine not be a good choice?
     
11. What is the advantage of t-PA (tissue plasminogen activator) over streptokinase?
     
12. What are the big disadvantages of t-PA in treating saddle thrombus?
    
    
    
    
     

ANSWERS

1. A necropsy study reported the following statistics on cats w/cardiomyopathy showing evidence of saddle thrombus:  48% of cats w/HCM were affected, 29% cats w/RCM, 25% w/DCM, & 14% w/excess moderator bands.
   
   Because this is a post mortem study, real percentages are probably lower but HCM seems to be associated w/the most saddle thrombi.
   
   
   
   
    
2. It can take up to 14 days to begin to see improvement (most are sooner) & up to 6 weeks to see how much function will be recovered (most max out by 3 weeks).  It is estimated that 50% will regain ability to walk.
   
   (Is this correct, Paul?  At what point does the ischemic pain go away?  If it looks like it's going to be a while, at what point can the cat be sent home to recover?)
   
   
   
   
    
3. One can expect a second episode 2-4 months after the first episode.  (Like in 100% of cases?)
   
   
   
   
    
4. Aspirin inhibis cyclooxygenase irreversibly.
   
   
   
   
    
5. Heparin works by activating anti-thrombin III which in turn neutralizes clotting factors 12, 11, 10, & 9.  The homeostasis of the body is thus shifted in favor of thrombolysis.  Heparin does not dissolve the clot itself. 
   
   
   
   
    
6. There are a few findings that are considered predictive. One would be a big old clot in the left atrium (the "mother thrombus" is usually located in the left atrium - the saddle thromus is its "child." :) Another finding would be a highly echogenic swirling pattern in the left atrium (indicates turbulence/blood stasis necessary for clot formation. 
   
   What they get most excited about at Angell is a left atrium: aorta ration of 2 or greater.  They put these guys on warfarin whether or not they've had a previous episode or not.
   
   
   
   
    
7. Angell is still getting 43% recurrence. They also see hemorrhage in 20% of cats (minor & major being lumped together in here.)  They feel that rigorous monitoring (One week hosp w/daily PTs, then 2x weekly PTs after discharge, then weekly, then finally every 8 weeks) will avoid major bleeds.
   
   Goal PT is 1.3-1.6x normal.
   
   
   
   
    
8. Collateral circulation from the epaxial artery & the spinal artery are able to continue circulation if the aorta is ligated. If there is a physical thrombus sitting in the aorta, vasoactive substances are released which constrict the collateral circulation.
   
   
   
   
    
9. In warfarin therapy PTs are the tests used in monitoring therapy.  Because of laboratory variations in the thromboplastins used something called the International Normalizatio Ratio (INR) has been developed.
   
   INR= (PT of the patient - PT control)^ISI
   
   ( The ISI is an exponent)
   
   ISI = International Sensitivity Index of the thromboplastin used. This number comes from the manufacterer & you should use one between 2 & 3 if you are using a kit for PT)
   
   
   
   
    
10. Let's assume we are not treating concurrent CHF - just the thrombus. Hydralazine may be a better dilator of splanchnic, coronary, cerebral & renal vessels than muscular vessels.  It might not vasodilate the area you want.  Hydralazine is an arteriolar dilator & we think it works by inducing an increase in local prostacyclin levels.
    
    
    
    
     
11. When it comes to activating plasminogen, we only want to activate the fibrin bound plasminogen.  Joe Plasminogen circulating around doesn't need activation & the last thing we need is to initiate a cascade that could start DIC.  Streptokinase activates any plasminogen it finds. T-PA only activates the fibrin bound kind.
    
    
    
    
     
12. One very big disadvantage is cost. The stuff costs more than my car.  Another big disadvantage is that eventhough 43% of cats were walking within 48 hours, approx. 50% mortality was seen.  Alot of this was felt to be from reperfusion injury.  Not good.
    
    (So, Paul, how do you personally treat these guys?)