Blood Toxicants Flashcards
What are some non-anticoagulant rodenticides?
- bromethalin
- cholecalciferol
- strychnine
- zinc phosphine
What is the pathophysiology of anticoagulant rodenticides?
- inhibits vitamin K epoxide reductase in the liver, which is responsible for activating vitamin K
- this inhibits the production vitamin K-dependent clotting factors (II, VII, IX, X) using vitamin K-dependent carboxylase
- depletion of the remaining existing factors causes bleeding within 3-5 days post-exposure
What is the difference between 1st and 2nd generation anticoagulant rodenticides?
1st = short-acting, less potent, shorter half-life
2nd = long-acting, more potent, longer half-life
How long does it take for a toxicant to be cleared from the body?
5 half-lives —> determines length of treatment
LONG-ACTING ACRs take ~30 days to be cleared
What does LD50 not give information about?
minimum toxic dose —> there is no good info on MTD and MLD of ACRs
What is the rule of tens? Why does this not typically apply to anticoagulant rodenticides?Q
assumes minimum lethal dose is 1/10 the LD50 and minimum toxic dose is 1/10 the MLD
very unscientific, often incorrect - death is often determined by where bleeding occurs and animals have died after ingesting much less than 1/10 the LD50
When do clinical signs of anticoagulant rodenticide toxicity start? What are signs associated with? What do they depend on?
DELAYED - 3-5 days post-ingestion caused by the depletion of the remaining circulating active factors
bleeding - can occur anywhere
where the bleeding is occuring - internal vs. external, location
What diagnostic tests can be used to diagnose anticoagulant rodenticide toxicity?
ACT, aPTT - 95% depletion of intrinsic pathway factors (IX)
OSPT - quick depletion of extrinsic pathway factor VII, which has the shortest half-life
What 4 things may be seen on CBC following anticoagulant rodenticide toxicity? What is radiography and ultrasonography used for? Thoracocentesis/abdominocentesis?
- anemia - mild to severe, regenerative
- thrombocytopenia
- neutrophilia
- hypoproteinemia
locates site of internal bleeding
identifies the type and cause of effusion
What in-house analyses can be used to diagnose anticoagulant rodenticide toxicity?
aPTT, OSPT, ACT
How does the activated clotting time (ACT) test work?
severe depletion (95%) of vitamin K-dependent anticoagulant factors must occur to observe a prolonged clotting time - takes longer to see effects on test
Is treatment indicated for low exposure dose of anticoagulant rodenticide? Why? What should be assumed?
YES - no good MTD information, dogs have died at low doses
worst case scenario - assume ingestion of a possible lethal dose
What is the goal to anticoagulant rodenticide toxicity treatment? How is this done? What can increase absorption of the antidote?
activate coagulation factors
oral active vitamin K1 (phytonadione) - NO IV OR IM, causes anaphylaxis, hematomas, and pain
fatty meals
How long does it take for vitamin K1 to work?
~24 hr - NOT a clotting agent, will not stop active bleeding right away
What is the recommended duration of vitamin K treatment?
depends on the type and half-life of the anticoagulant - treat until ACR is eliminated from the body:
- 4 weeks or longer for long-acting anticoagulants
- 10 days to 2 weeks for warfarin
How should vitamin K treatment be done if the type of anticoagulant rodenticide is unknown?
assume it is long-lasting or treat for 10 days, then stop for a few days and retest clotting times
What is the major dilemma with vitamin K1 treatment?
treatment for large dogs is very expensive - if exposure dose it low and decontamination appears successful, is treatment necessary?
- recheck clotting profile in 48-72 hr
Can multi-vitamin supplements aid in treatment? Vitamin K3?
no - concentration of K1 is not high enough
no - not active, takes time and many adverse signs have been documented: renal failure, Heinz body anemia, methemoglobinemia
If a lung bleed is suspected, what diagnostics are recommended?
- chest radiographs: mild patchy areas of pulmonary infiltrates denser than air
- CBD, biochemical profiles: normal
- coagulation tests: ACT, OSPT, aPTT prolonged
What is absolutely necessary for lung bleed treatment? What supportive treatment is recommended?
- immediate transfusion with coagulation factors in fresh frozen plasma, frozen plasma, or fresh whole blood
- high dose vitamin K1 treatment for ~ 1 month
oxygen, cage rest, monitor lungs/breathing, chest taps
What diagnostics are recommended in cases of suspected severe anemia and coagulation defects? What 3 differentials should be at the top of the list?
- biochemistry profile: normal
- CBC: severe anemia (PCV <10%), macrocytosis, reticulocytosis, polychromasia (regenerative), leukocytosis, increased platelets
- coagulation tests: ACT, aPTT, OSPT dramatically prolonged
- radiographs: NSF
blood loss, hemolytic anemia, ehrlichiosis
What treatment is necessary for severe anemia and coagulation defects? What supportive care is recommended?
- blood transfusion with coagulation factors AND RBCs from fresh whole blood or packed RBCs + plasma
- vitamin K1: assume treatment for 1 month
oxygen, rest, gentle handling
What medications are contraindicated in the event of anticoagulant rodenticide poisoning? What should owners be informed about treatment?
NSAIDs
MUST finish ENTIRE vitamin K1 prescription - early termination can kill the animal
Although vitamin K is considered the antidote for anticoagulant rodenticide toxicity, what is the considered the most important treatment of active bleeding?
blood transfusion containing active clotting factors
- vitamin K1 does NOT provide immediate active clotting factors, it enables the body to produce the factors in ~ 24 hrs
What is the recommended treatment of suspected anticoagulant rodenticide toxicity lacking active bleeding? With active bleeding?
early case - vitamin K1 until ACR is eliminated completely (5 half-lives)
vitamin K1 AND transfusion - allows production of new clotting factors and stops active bleeding by providing clotting factors and RBCs
When is decontamination for anticoagulant rodenticide toxicity too late?
if clinical signs are present (3-5 days post-exposure)
What are the most significant sources of anticoagulant poisoning in horses and cattle?
HORSES - therapeutic warfarin, rat poison placed in barn
CATTLE - moldy sweet clover (dicoumarol)
What is unique about anticoagulant poisoning in horses?
factor IX may be depleted before factor VII, so aPTT may increase first
