QUESTIONS

1. What clotting factors aret he so-called "K factors" & why are they called "K factors?"
    
2. What enzyme do the anticoagulant rodenticides inactivate?
    
3. In anticoagulant rodenticide toxicity, what changes do you expect in:
   
   a) PT
   b) PTT
   c) ACT
    
4. When giving K1 therapeutically, what route is preferred?
    
5. What is meant by "second generation rodenticide?"
    
6. What clotting test should you run prior to discontinuing K1 therapy?
   
   
   
   
    

ANSWERS

1. Factors 10, 9, 7, 2 are the K factors.  They are called the K factors because vitamin K is a cofactor in their carboxylation.  The carboxylation of the K factors is necessary if they are to bind calcium & if they can't bind calcium, they can't participate in blood clotting.  Each K factor protein ought to have 10-16 calcium binding sites on it. No vitamin K, no carboxylation, no calcium binding, no blood clotting.
   
   
   
   
    
2. In order for this to be an intelligent answer, you must understand how vitamin K is "recycled."  K1 is converted to K1 epoxide by K1 epoxidase.  (this is the reaction which carboxylates the K factors)  Next, K1 epoxide is then reduced to K1 quinone via K1 epoxide reductase.  (This is where the anticoagulant dudes act.)  The K1 quinone is taken back to K1 via diaphorase.The stuff you are giving when you treat anticoagulant rodenticide toxicity is K1 quinone.
   
   
   
   
    
3. a) PT tests extrinsic & common clotting pathways
   b) PTT tests intrinsic & common clotting pathways
   c) ACT tests intrinsic & common clotting pathways but not as sensitively as PTT
   
   All tests should be abnormal BUT PT will be abnormal first.  This is because factor 7 is in the extrinsic pathway & has the shortest half life of all the K factors.
   
   A better test is the Thrombotest or PIVKA test which tests for the presence of proteins found in the absence of K1 & for reduction in functional K factor levels.  You can buy this kit from Burroughs wellcome (about 50 tests for $100).
   
   
   
   
    
4. Well, oral is pretty good if your patient is stable enough.  SQ is pretty good if your patient is not stable enough for oral. So what's wrong with IM?  Think about it. Your patient can't clot.  Imagine the hemorrhage after an IM injection! What's wrong w/IV?  High percentage of cases get anaphylaxis after IV K1 treatment.
   
   
   
   
    
5. This refers to rodenticides used by Gene Roddenberry.  No.  Sorry.  Back up.  In the beginning, there was WARFARIN.  The problem with warfarin was that the rats had to come back & nibble on the bait multiple times.  Because of inconsistent nibbling, pretty soon there were warfarin-resistent rats.  The second generation rodenticides were meant to be lethal in one single meal.
   
   What does this mean for a dog or cat?  It's not as relevant as you might think.  The indanediones are a group of first generation rodenticides (diphacinone is a good example) for which the half life is very long (4-5 days).  Brodificoum, a second generation rodenticide also has a very long half life (6 days or so).  When we treat dogs & cats, we don't care so much about the generation of the rodenticide as much as we do about its half life. Both these 2 toxins mentioned here require prolonged treatment w/K1 (like 3 or 4 weeks).
   
   
   
   
    
6. The PT is the best clotting test to run - again, it is because of the short half life of factor 7.