| ANTICOAGULANT THERAPY MONITORING |  Email this article Printer friendly page |
Standard Unfractionated Heparin (UFH)
Heparin-induced Thrombocytopenia with Thrombosis (HIT)
Low Molecular Weight Heparin (LMWH)
Fondaparinux (Arixtra®, pentasaccharide)
Direct Thrombin Inhibitors (DTIs)
Monitoring Using Anti-Xa (download PDF)
Warfarin (CoumadinÒ)
Indications for warfarin
- Treatment of arterial and venous thrombosis to prevent clot propagation
- Prevention of thromboembolic disease in thrombophilia, atrial fibrillation, mechanical heart valves, and high-risk surgery
- Prevents the vitamin K dependent gamma-carboxylation of factors II, VII, IX, and X, proteins C and S, slowing thrombin production
- 5-10 mg/day with no loading dose. Must be monitored due to unpredictable half-life.
Affected by many drugs and dietary variation - Requires 2-7 days to reach therapeutic levels. To achieve immediate anticoagulation, begin with heparin.
- PT generates the international normalized ratio (INR) by this formula:
Target INRsWhere…INR = (Patient PT/MRI PT) ISI
PT = prothrombin time in seconds
MRI = geometric mean of reference interval
ISI = international sensitivity index supplied by reagent manufacturer
- Post-myocardial infarction, most therapy and prophylaxis: INR 2.0-3.0
- Mechanical heart valves: INR 2.5-3.5
- Daily until INR is therapeutic twice at least 24 hours apart
- Twice a week for 2 weeks, then once a month until therapy is complete
| No bleeding |
Warfarin dosage |
| INR 3.5-5 |
Decrease, do not stop drug |
| INR 5-8 |
Decrease, consider 1 mg K PO |
| INR 5-8, bleeding risk high |
Decrease, give 2.5-5 mg K PO or1 mg SQ |
| INR > 8 |
Stop drug, give 2.5-5 mg K PO or 2-3 mg SQ |
| INR > 8, bleeding risk high |
· Stop drug, give 5 mg K PO or 3-5 mg SQ · Consider 10 mL/kg FFP or 25 U/kg PCCs (p. 36) |
| Minor bleeding |
Warfarin dosage |
| INR 2-3.5 |
Decrease, look for site |
| INR 3.5-5 |
Stop drug, reinstitute at lower dose |
| INR 5-8 |
Stop drug, give 2.5 mg K PO or 1 mg SQ |
| INR 5-8, thrombotic risk high |
Stop drug, do not give K |
| INR > 8 |
· Stop drug, give 5 mg K PO or 2-5 SQ · Consider 10 mL/kg FFP or 25 U/kg PCCs (p. 36) |
| Major bleeding |
Warfarin dosage |
| INR 2-3.5 |
Stop drug, give 5 mg SQ K or IV, repeat as necessary, look for bleeding site |
| INR 3.5-5 |
· Stop drug, give 5-10 mg K SQ or IV, repeat · Consider 10-15 mL/kg FFP or 25-50 U/kg PCCs (p. 36) |
| INR 5-8 |
· Stop drug, give 5-10 mg K SQ or IV, repeat · Give 15 mL/kg FFP or 25-50 U/kg PCCs (p. 36) |
| INR >8 |
· Stop drug, give10 mg K SQ or IV, repeat 6h · Give 15 mL/kg FFP or 25-50 U/kg PCCs (p. 36) |
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Standard Unfractionated Heparin (UFH)
Indications for UFH
- Treatment of arterial and venous thrombosis to prevent clot propagation
- Increases the inhibitory effect of antithrombin on the serine proteases thrombin, IXa, Xa, XIa, and XIIa with greatest effect upon thrombin
- UFH clearance varies by individual and requires routine monitoring
- 80 IU/kg bolus, 8 IU/kg/h IV started concurrently with warfarin
- Discontinue after 5 days if the INR has been therapeutic for at least 24 hours
- Assay 4-6 hours after bolus dosage and every 24 hours thereafter; if dose adjustment is needed, 6 hours after changing IV infusion
- UAB target for prophylaxis: 51 - 70 s; based upon anti-Xa of 0.1 to 0.4 U/mL
- UAB target for therapy: 71 - 105 s; based upon anti-Xa of 0.3 to 0.7 U/mL
- Target PTT interval varies with reagent lot; last updated 10/26/12. Contact UAB special coagulation laboratory for current values.
- Check PLT count daily to detect heparin induced thrombocytopenia (HIT)
- If count drops 30-50%, consider HIT, withdraw heparin, start alternative anticoagulant, order confirmatory test for HIT
- Stop heparin and monitor PTT. Heparin half-life is approximately 30 minutes. If bleeding is severe, consider protamine sulfate (1 mg/100 units heparin)
- FFP does not reverse heparin effect
Heparin-induced Thrombocytopenia with Thrombosis (HIT)
From 1-5% of patients receiving unfractionated heparin develop HIT. An antibody to heparin-bound platelet factor 4 (PF4) that activates platelets causes HIT. HIT is a major source of morbidity and mortality, and must be rigorously guarded against. Daily platelet counts throughout and following heparin therapy are the primary defense. A 30-50% decrease, even when the count remains within the normal range, may signal the onset of HIT. Laboratory confirmation consists of an immunoassay for the anti-heparin-PF4 antibody. This assay requires several hours and yields a relatively high false positive rate, thus is considered confirmatory but not diagnostic. When the clinical suspicion is high, heparin should be replaced with one of the direct thrombin inhibitors Lepirudin or Argatroban, until the clinical situation is elucidated.
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Low Molecular Weight Heparin (LMWH)
Enoxaparin, Tinzaparin (Lovenox)
Indications for LMWH
- Prevention or treatment of thromboembolic disease
- Increases the inhibitory effect of antithrombin on the serine proteases thrombin and Xa with greatest effect upon Xa
- LMWH clearance is predictable and requires little monitoring in uncomplicated thrombosis; enoxaparin accumulates in renal insufficiency
- Prophylaxis: 40 mg SQ once a day (for morbidly obese, may need 60 mg)
- Therapeutic: 1 mg/kg q12h (maximum of 150 mg)
Fondaparinux (Arixtra®, pentasaccharide)
Dosage
- Prophylaxis: 2.5 mg SQ once a day
- Therapeutic: Not established
- Use chromogenic anti-Xa heparin assay; PTT is insensitive
- Assay not necessary in uncomplicated treatment situation
- Assay needed for infants, children, obese or underweight patients, or those with renal disease, long-term treatment, pregnancy, or unexpected bleeding or thrombosis
- Collect blood specimen 4 h after a subcutaneous dose
- Pentasaccharide target: 0.14 to 0.19 mg/L
Direct Thrombin Inhibitors (DTIs): Argatroban and Lepirudin
DTI indications
- Substitute for heparin when HIT is suspected or confirmed. Even when HIT's only manifestation is thrombocytopenia and heparin is stopped, risk of thrombosis in subsequent 30 days approaches 50% unless alternative anticoagulant is used.
- Lepirudin: 0.4 mg/kg slowly IV, then 0.15 mg/kg continuous infusion for 2-10 days depending on indication
- Argatroban: 2 µg/kg/min IV
- Lepirudin: 20 minutes
- Argatroban: 39-51 minutes
- PTT is used to prevent bleeding or thrombosis
- Lepirudin: collect blood four (4) hours after initial dosage, adjust dosage to PTT 1.5-3.0 x mean of reference interval
- Argatroban: collect blood two (2) hours after initial dosage, adjust dosage to PTT 1.5-3.0 x mean of reference interval
- Lepirudin accumulates in kidney failure
- Argatroban accumulates in liver failure
- Do not start in patients with PTT longer than 2.5 x mean of reference interval
- In HIT, warfarin may be introduced when platelet count starts to increase but DTIs should be continued until platelet count normalizes. After 4-5 days of warfarin, if platelet count is normal and PT is therapeutic, stop DTI for a few hours and recheck INR. If between 2-3, it is safe to discontinue DTI.
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