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Anticoagulant
Therapy
Warfarin
(Coumadin®)
Unfractionated Heparin (UFH)
Low Molecular Weight Heparin (LMWH)
Argatroban or Lepirudin
Warfarin
(Coumadin®)
Indications
for Warfarin
* Treatment of arterial and venous thrombosis to prevent clot
propagation.
* Prevention of venous thromboembolic disease in various conditions.
*
Treatment may be short- or long-term.
Mechanism
of Action
Prevents the vitamin K dependent gamma-carboxylation of factors
II, VII, IX, and X, proteins C and S. This slows thrombin
production.
Dosage
* 5-10 mg/day with no loading dose. Must be monitored due
to unpredictable half-life.
* Affected by many drug and dietary interferences.
* Requires 5 days to reach therapeutic or prophylactic levels.
For immediate anticoagulant effect, begin with simultaneous
heparin.
Laboratory
Monitoring: The INR
Prothrombin time test generates the international normalized
ratio (INR) by this formula:
| INR
= |
(Patient
PT/MRI PT)E ISI |
Where…
PT = prothrombin time in seconds
MRI = geometric mean of reference interval
ISI = international sensitivity index supplied by manufacturer
of PT reagent
Target
Dosages
* Most therapy and prophylaxis: INR 2.0-3.0
* Post-MI and mechanical heart valves: INR 2.5-3.5
Laboratory
Monitoring Interval
* Daily until INR is therapeutic twice at least 24 hours apart
* Two times a week for 2 weeks
* Once monthly until therapy is complete
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Unfractionated
Heparin (UFH)
Indications
for UFH Same as Warfarin
* Treatment of arterial and venous thrombosis to prevent clot
propagation.
* Prevention of thromboembolic disease in atrial fibrillation,
mechanical heart valves, and high-risk surgery.
Mechanism
of Action
* Activates plasma antithrombin, which immediately binds and
inactivates serine proteases thrombin, IXa, Xa, XIa, and XIIa
with greatest effect upon thrombin.
* UFH clearance varies by the individual and requires routine
monitoring.
Dosage
* 80 IU/kg bolus, 8 IU/kg/h IV with warfarin
* Discontinue after 5 days if goal INR reached
Laboratory
Monitoring: PTT and Platelet count
* Assay 4-6 hours after bolus, then every 24 hours
* UAB target for prophylaxis: 50-85 s
* UAB target for therapy: 75-120 s
* Platelet count once a day; if count drops 50%, consider
HIT, withdraw UFH, switch to Argatroban or Lepirudin
Overdose
*Stop UFH; give protamine sulfate 1 mg/100 U heparin in circulation
by anti-Xa assay
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Low
Molecular Weight Heparin (LMWH)
Indications
for LMWH
Prevention of thromboembolic disease in thrombophilia, high-risk
surgery and other conditions.
Mechanism of Action
* Upregulates plasma antithrombin, which immediately binds
and inactivates serine proteases thrombin, IXa, Xa, XIa, and
XIIa with greatest effect upon Xa.
* LMWH clearance is predictable and requires little monitoring
in uncomplicated thrombosis.
Dosage
* Prophylaxis: 40 mg SC once a day
* Treatment: 1 mg/kg q12h
Laboratory
Monitoring: Chromogenic anti-Xa
* Assay only for infants, children, obese or underweight,
renal disease, long-term, pregnancy unexpected bleeding, or
thrombosis
* Target for prophylaxis: 0.2 to 0.4 anti-Xa heparin U
* Target for therapy: 0.5-1.0 anti-Xa heparin U
* Platelet count once a day
* If count drops 50%, consider HIT, withdraw LMWH, switch
to Argatroban or Lepirudin
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Argatroban
or Lepirudin
Indications
for LMWH
Substitute for heparin when heparin-induced thrombocytopenia
with thrombosis is suspected.
Mechanism of Action
* Direct antithrombin
Dosage
* Lepirudin: 0.4 mg/kg slowly IV, then 0.15 mg/kg continuous
2-10 days
* Argatroban: 2 µg/kg/min
Laboratory
Monitoring: PTT
* Lepirudin: collect blood 4 hours after initial dosage, adjust
dosage to PTT 1.5-3.0 x mean of reference interval
* Argatroban: collect blood 2 hours after initial dosage,
adjust dosage to PTT 1.5-3.0 x mean of reference interval
* Do not start in patients with baseline PTT longer than 2.5
x mean of reference interval.
* Continue with once daily PTT or more often if there is renal
impairment.
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