Tox: anticoagulants

Question 1

MOA of warfarin

Answer 1

Blocks conversion of vitamin K to its active form, preventing formation of vitamin K dependent clotting factors (2,7,9,10).
Effect is delayed until preformed stores of clotting factors are depleted (~15hrs).
Also blocks formation of antithrombotic proteins C&S so may be prothrombotic until K-dependent factors are depleted.

Question 2

Duration of action of warfarin

Answer 2

up to 6d

Question 3

Potential onset timing of bleeding in the setting of warfarin overdose

Answer 3

PT and INR need to be monitored for 3-4 days.

Question 4

How/when to treat warfarin overdose/elevated INR

Answer 4

AC if within 1hr presentation.
If no clinically significant bleeding:
- INR <5: lower/skip dose, resume once therapeutic.
- INR 5-9: omit next 1-2 doses OR skip dose and give 1-2mg vitamin K PO.
- INR >9: hold warfarin. Higher dose of vitamin K (5-10mg PO). Resume at lower doses once INR therapeutic.

Serious bleeding at any INR: hold warfarin, vitamin K 10mg slow IV, FFP or PCC, or alternatively recombinant factor VIIa

Question 5

Onset of vitamin K for warfarin

Answer 5

Reverses coagulopathy after several hours. Should NOT be administered prophylactically after overdose.

Question 6

Difference between using PCC (octaplex) and FFP for warfarin reversal

Answer 6

FFP: Contains all factors. 10-15mg/kg will restore factors levels to >/30% of normal.

PCC: Contains only vitamin K dependent clotting factors. Allows for complete reversal of anticoagulation.

Question 7

Potential complication of vitamin K therapy

Answer 7

anaphylactoid reaction

Question 8

Describe warfarin induced skin necrosis, how to avoid and how to treat

Answer 8

Occurs 3-8d after initiating warfarin in pts with protein C deficiency (transient hypercoagulable state leads to thrombosis of cutaneous vessels).
Prevented by coadministration of heparin during initiation of warfarin therapy.
Tx with discontinuation warfarin, initiation of heparin.

Question 9

MOA of heparin

Answer 9

binds antithrombin III –> heparin/antithrombin III complex –> inhibition multiple steps in intrinsic and extrinsic pathways.

Question 10

How LMWH is different from reg heparin

Answer 10

Longer half life, greater bioavaialability, greater activity against factor Xa.

Question 11

Expected change to coags/labs with heparin

Answer 11

Elevation of aPTT levels.

May see elevation of anti-Xa levels.

Question 12

Antidote for heparin/LMWH

Answer 12

protamine sulfate

Question 13

When should the antidote for heparin be given?

Answer 13

Severe bleeding complications only in the setting of heparin and LMWH use (although only partially inactivates LMWH)

Question 14

Risk associated with giving the antidote to heparin

Answer 14

anaphylaxis

Question 15

How much antidote should be given for each 100U of UFH

Answer 15

1mg protamine sulfate neutralizes 100U of UFH

Question 16

Describe HIT

Answer 16

Platelet activation/consumption due to antibodies against heparin-platelet complex.
10X more common with UFH.
Onset typically 5-10d after exposure (sooner if previous exposure or up to 3wks after stopping therapy).
Use 4T score to diagnose:
1) Thrombocytopenia: should see plt fall by >50%.
2) Timing: clear onset between heparin exposure and symptoms onset (5-10d if first exposure).
3) Thrombosis/sequelae: New thrombosis or skin necrosis.
4) other causes of thrombocytopenia: apparent or not.