Direct Thrombin Inhibitors and Fondaparinux

Question 1

Parenteral Direct Thrombin Inhibitors bind to

Answer 1

Thrombin Reversibly

Question 2

Parenteral DTIs prevent

Answer 2

Both initiation of clots and propagation of clots by inhibiting both clot-bound and free -floating thrombin.

Heparin only binds to free-floating thrombin and therefore can only inhibit the initiation of clots.

Also prevent thrombin-mediated platelet activation.

Question 3

Four T’s of the 4 T Score

Answer 3

Thrombocytopenia, oTher cause of thrombocytopenia (ex. sepsis, ventilator), Timing of thrombocytopenia, Thrombosis

Question 4

Drug of choice for PCI anticoagulation in patients with higher risk of bleeding

Answer 4

Bivalirudin > UFH

Question 5

Drug of choice for PCI anticoagulation in patients with NSTEMI

Answer 5

Bivalirudin

Question 6

Drug of choice for PCI anticoagulation in patients with STEMI at higher risk of ischemic events

Answer 6

Unfractionated heparin

Question 7

Drug of choice for PCI anticoagulation in patients with acute MI and HIT

Answer 7

Argatroban

Question 8

When to draw aPTT for DTIs

Answer 8

2 - 4 hours after the start of infusion, every 2 - 4 hours until therapeutic, and after any dose adjustments; monitoring can be decreased to once or twice daily once the patient has two consecutive therapeutic levels

Question 9

When to recheck ACT for DTIs

Answer 9

5 - 10 minutes after dose adjustments

Question 10

ACT goal for Argatroban

Answer 10

300 - 450 seconds

Question 11

ACT goal for Bivalirudin (PCI)

Answer 11

200 - 250 seconds

Question 12

When to start warfarin after HIT

Answer 12

Once the platelet count has recovered to > 150 x 10^3/mcL or to patient’s baseline

Question 13

Overlap of warfarin and DTI post-HIT

Answer 13

> /= 5 days and until INR is within target range for a period of time; INR should be rechecked after DTI discontinuation to know what the INR is solely on warfarin

Question 14

Warfarin and Argatroban overlap post-HIT

Answer 14

> /= 5 days and:
If infusion rate is = 2 mcg/kg/min, continue to overlap until INR is > 4.0
If infusion rate is > 2 mcg/kg/min, first reduce infusion rate to = 2 mcg/kg/min
Better to use chromogenic factor X activity assay with goal 20 - 40% factor X activity (corresponds to INR 2 - 3)

Question 15

Warfarin and Bivalirudin overlap post-HIT

Answer 15

> /= 5 days and until the INR is > 3.0 for at least 24 hours

Question 16

DTI adverse effects

Answer 16

bleeding, hypotension, angina, cardiac arrest, headache, fever, nausea, V-tach, vomiting, infection, coughing

Question 17

Drugs of choice in pregnant patient with HIT

Answer 17

Fondaparinux (danaparoid not available in US, lepirudin not sold)

Question 18

DTIs in breastfeeding

Answer 18

Not recommended

Question 19

Fondaparinux pharmacokinetics and bioavailability (ADM)

Answer 19

Linear pharmacokinetics, 100% bioavailability SQ, peak plasma concentration in 2 - 3 hours, steady state in 3 - 4 doses, not hepatically metabolized, highly protein bound

Question 20

Fondaparinux elimination is dependent on

Answer 20

Renal function, age, body weight

Question 21

Fondaparinux duration for orthopedic surgery VTE prophylaxis

Answer 21

10 - 14 days minimum

Question 22

When to use Fondaparinux for VTE prophylaxis in general and abdominal-pelvic surgery patients

Answer 22

When VTE risk is high, UFH and LMWH are not viable options, and patient is not at high risk for major bleeding

Question 23

ACCP guideline recommendation for Fondaparinux and HIT

Answer 23

Fondaparinux can be used on a patient with a remote history of HIT if non-HIT associated thrombosis

Question 24

If Fondaparinux is being used for ACS

Answer 24

Also use a thrombin inhibitor like UFH (85 units/kg bolus) or GPI (60 units/kg bolus) to avoid catheter related thrombosis

Try to avoid fondaparinux as initial anticoagulation for STEMI patients undergoing PCI

Question 25

Transitioning Fondaparinux to

a. Warfarin
b. other anticoagulants

Answer 25

a. 5 day overlap AND until INR is > 2 for 24 hours

b. 24 hours after the last dose

Question 26

Fondaparinux in breastfeeding

Answer 26

Not recommended

Question 27

ACT goal for Bivalirudin (CABG)

Answer 27

> 300 seconds

Question 28

Factors that can affect aPTT

Answer 28

Lupus anticoagulant, liver disease, consumptive coagulopathy, variations in endogenous factor levels