Direct Thrombin Inhibitors and Fondaparinux Flashcards
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
Bivalirudin
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
Argatroban
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
