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Part One: Warfarin Dosing Guidelines
Warfarin Dosing Information
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Individualize dose according to patient response
(as indicated by INR)
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Use of large loading dose not recommended*
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May increase hemorrhagic complications
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Does not offer more rapid protection
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Low initiation doses are recommended for elderly/frail/liver-diseased/malnourished
patients
Notes:
Three recommendations designed
to increase the safety of warfarin use are listed on this
slide.
Large loading doses (>10 mg)
are no longer recommended for the initiation of therapy. As
demonstrated in slide 17c, large loading doses cause an abrupt
and dramatic fall in Factor VII levels (close to 0%), but
do not speed up the reduction of Factors IX, X, or II compared
to lower doses. It still takes 4–5 days to get all of the
Vitamin K dependent coagulation factors down to a therapeutic
range, at which time, therapy needs to overlap with heparin
therapy in patients with venous thrombotic disease. Because
Factor VII levels can fall so low with large loading doses,
there is a risk of hemorrhage during the first few days of
therapy. Furthermore, large loading doses cause a precipitous
fall in Protein C (a Vitamin K dependent coagulation inhibitor
that also has a short half life of about six hours), and if
this protein falls significantly during early therapy before
all of the Vitamin K dependent factors are decreased, one
could potentially develop a hypercoagulable state before a
hypocoagulable state develops. Consequently, initiation of
therapy today is recommended to start with 5 mg of warfarin
(in some cases 10 mg may be used initially). Thereafter, subsequent
doses are based on the INR response. For patients who may
already have impaired coagulation (liver disease), who may
have low levels of Vitamin K (malnourishment), or may be at
a greater risk of bleeding, it is recommended to start with
even lower initial doses such as 2.5 mg of warfarin.
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