Blood Toxicants

Question 1

What are some non-anticoagulant rodenticides?

Answer 1

• bromethalin
• cholecalciferol
• strychnine
• zinc phosphine

Question 2

What is the pathophysiology of anticoagulant rodenticides?

Answer 2

• 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

Question 3

What is the difference between 1st and 2nd generation anticoagulant rodenticides?

Answer 3

1st = short-acting, less potent, shorter half-life

2nd = long-acting, more potent, longer half-life

Question 4

How long does it take for a toxicant to be cleared from the body?

Answer 4

5 half-lives —> determines length of treatment

LONG-ACTING ACRs take ~30 days to be cleared

Question 5

What does LD50 not give information about?

Answer 5

minimum toxic dose —> there is no good info on MTD and MLD of ACRs

Question 6

What is the rule of tens? Why does this not typically apply to anticoagulant rodenticides?Q

Answer 6

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

Question 7

When do clinical signs of anticoagulant rodenticide toxicity start? What are signs associated with? What do they depend on?

Answer 7

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

Question 8

What diagnostic tests can be used to diagnose anticoagulant rodenticide toxicity?

Answer 8

ACT, aPTT - 95% depletion of intrinsic pathway factors (IX)

OSPT - quick depletion of extrinsic pathway factor VII, which has the shortest half-life

Question 9

What 4 things may be seen on CBC following anticoagulant rodenticide toxicity? What is radiography and ultrasonography used for? Thoracocentesis/abdominocentesis?

Answer 9

1. anemia - mild to severe, regenerative
2. thrombocytopenia
3. neutrophilia
4. hypoproteinemia

locates site of internal bleeding

identifies the type and cause of effusion

Question 10

What in-house analyses can be used to diagnose anticoagulant rodenticide toxicity?

Answer 10

aPTT, OSPT, ACT

Question 11

How does the activated clotting time (ACT) test work?

Answer 11

severe depletion (95%) of vitamin K-dependent anticoagulant factors must occur to observe a prolonged clotting time - takes longer to see effects on test

Question 12

Is treatment indicated for low exposure dose of anticoagulant rodenticide? Why? What should be assumed?

Answer 12

YES - no good MTD information, dogs have died at low doses

worst case scenario - assume ingestion of a possible lethal dose

Question 13

What is the goal to anticoagulant rodenticide toxicity treatment? How is this done? What can increase absorption of the antidote?

Answer 13

activate coagulation factors

oral active vitamin K1 (phytonadione) - NO IV OR IM, causes anaphylaxis, hematomas, and pain

fatty meals

Question 14

How long does it take for vitamin K1 to work?

Answer 14

~24 hr - NOT a clotting agent, will not stop active bleeding right away

Question 15

What is the recommended duration of vitamin K treatment?

Answer 15

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

Question 16

How should vitamin K treatment be done if the type of anticoagulant rodenticide is unknown?

Answer 16

assume it is long-lasting or treat for 10 days, then stop for a few days and retest clotting times

Question 17

What is the major dilemma with vitamin K1 treatment?

Answer 17

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

Question 18

Can multi-vitamin supplements aid in treatment? Vitamin K3?

Answer 18

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

Question 19

If a lung bleed is suspected, what diagnostics are recommended?

Answer 19

• chest radiographs: mild patchy areas of pulmonary infiltrates denser than air
• CBD, biochemical profiles: normal
• coagulation tests: ACT, OSPT, aPTT prolonged

Question 20

What is absolutely necessary for lung bleed treatment? What supportive treatment is recommended?

Answer 20

• 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

Question 21

What diagnostics are recommended in cases of suspected severe anemia and coagulation defects? What 3 differentials should be at the top of the list?

Answer 21

• 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

Question 22

What treatment is necessary for severe anemia and coagulation defects? What supportive care is recommended?

Answer 22

• 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

Question 23

What medications are contraindicated in the event of anticoagulant rodenticide poisoning? What should owners be informed about treatment?

Answer 23

NSAIDs

MUST finish ENTIRE vitamin K1 prescription - early termination can kill the animal

Question 24

Although vitamin K is considered the antidote for anticoagulant rodenticide toxicity, what is the considered the most important treatment of active bleeding?

Answer 24

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

Question 25

What is the recommended treatment of suspected anticoagulant rodenticide toxicity lacking active bleeding? With active bleeding?

Answer 25

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

Question 26

When is decontamination for anticoagulant rodenticide toxicity too late?

Answer 26

if clinical signs are present (3-5 days post-exposure)

Question 27

What are the most significant sources of anticoagulant poisoning in horses and cattle?

Answer 27

HORSES - therapeutic warfarin, rat poison placed in barn

CATTLE - moldy sweet clover (dicoumarol)

Question 28

What is unique about anticoagulant poisoning in horses?

Answer 28

factor IX may be depleted before factor VII, so aPTT may increase first