- In patients with
heparin-induced thrombocytopenia (HIT), warfarin should be initiated
only after the platelet count has recovered substantially (e.g., to
>100 x 109/L or to pre-HIT baseline value).
·
Argatroban and warfarin therapy should overlap for
4 or 5 days before warfarin is used as monotherapy in patients with HIT.
- Warfarin
should be initiated with the expected daily dose and high initial
warfarin doses should be avoided in patients with HIT.
- The
INR should be monitored daily while Argatroban and warfarin are
co-administered.
- Traditional
monitoring of warfarin therapy using the International Normalized Ratio
(INR) is elevated and confounded during both monotherapy and concurrent
therapy with direct thrombin inhibitors (DTIs) such as Argatroban.
- The combination of
Argatroban and warfarin does not cause further reduction in the vitamin
K dependent factor Xa activity than that which is seen
with warfarin alone, and the elevated INR that occurs during therapy
with Argatroban does not result in an increased risk of major bleeding
or a difference in efficacy outcomes in patients with HIT.
- The relationship
between INR during combination therapy compared to warfarin alone is
dependent on both the dose of Argatroban and the
thromboplastin reagent used.
- For
commonly used ISI values in the range of 0.88 to 1.78, and doses of
Argatroban < 2 mcg/kg/min, the INR on warfarin alone can be
predicted from the INR on combination therapy. Under these
circumstances, Argatroban can be discontinued when the INR is > 4 on
combined therapy. An INR of 4 on
the combination of Argatroban and warfarin would be expected to
correspond to an INR within the range of 2 to 3 on warfarin monotherapy.
After Argatroban is discontinued, the INR measurement should be repeated
in 4 to 6 hours. If the repeat INR is below the desired therapeutic
range, the infusion of Argatroban should be resumed and the procedure
should be repeated daily until the desired therapeutic INR on warfarin
alone is reached.
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