Direct Thrombin Inhibitors and Fondaparinux Flashcards Preview

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Parenteral Direct Thrombin Inhibitors bind to

Thrombin Reversibly


Parenteral DTIs prevent

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.


Four T's of the 4 T Score

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


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

Bivalirudin > UFH


Drug of choice for PCI anticoagulation in patients with NSTEMI



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

Unfractionated heparin


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



When to draw aPTT for DTIs

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


When to recheck ACT for DTIs

5 - 10 minutes after dose adjustments


ACT goal for Argatroban

300 - 450 seconds


ACT goal for Bivalirudin (PCI)

200 - 250 seconds


When to start warfarin after HIT

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


Overlap of warfarin and DTI post-HIT

>/= 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


Warfarin and Argatroban overlap post-HIT

>/= 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)


Warfarin and Bivalirudin overlap post-HIT

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


DTI adverse effects

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


Drugs of choice in pregnant patient with HIT

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


DTIs in breastfeeding

Not recommended


Fondaparinux pharmacokinetics and bioavailability (ADM)

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


Fondaparinux elimination is dependent on

Renal function, age, body weight


Fondaparinux duration for orthopedic surgery VTE prophylaxis

10 - 14 days minimum


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

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


ACCP guideline recommendation for Fondaparinux and HIT

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


If Fondaparinux is being used for ACS

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


Transitioning Fondaparinux to
a. Warfarin
b. other anticoagulants

a. 5 day overlap AND until INR is > 2 for 24 hours
b. 24 hours after the last dose


Fondaparinux in breastfeeding

Not recommended


ACT goal for Bivalirudin (CABG)

> 300 seconds


Factors that can affect aPTT

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