Warfarin

INTRODUCTION

 Their use is challenging because their therapeutic range is narrow and dosing is affected
by many factors including genetic variation, drug interactions, and diet.
 Time spent with a prothrombin time (PT)/international normalized ratio (INR) above the
therapeutic range increases the risk of bleeding, and time spent below the therapeutic
range increases the risk of thromboembolic complications, which these agents were
administered to prevent.

 Coagulation testing may reveal an underlying thrombophilia such as the antiphospholipid

syndrome (APS), which may artifactually increase the PT and/or aPTT, depending on the
assay characteristics.
contraindications to anticoagulation

 Active, clinically significant bleeding.

 Severe bleeding diathesis .
 Severe thrombocytopenia (platelet count <50,000/microL).
 Major trauma.
 Invasive procedure or obstetric delivery (recent, emergency, or planned).
 Previous intracranial hemorrhage.
 Intracranial or spinal tumor.
 Neuraxial anesthesia.
 Severe, uncontrolled hypertension.
Baseline testing

 Prior to starting warfarin, it is appropriate to obtain the following baseline testing, if not
already done:
 Prothrombin time (PT) with an international normalized ratio (INR) and activated partial
thromboplastin time (aPTT), to obtain a baseline value for monitoring and to identify any
underlying abnormalities.
 Complete blood count, including platelet count, to obtain a baseline and identify
thrombocytopenia.
 Serum creatinine, to estimate the glomerular filtration rate (GFR).
 Liver function tests, to identify potential alterations of warfarin metabolism (or hemostasis).
Initial dosing

 For patients starting warfarin therapy, we suggest an initial daily dose of ≤5 mg, rather than
higher doses or "loading" doses, unless the patient is known from previous experience to
require higher doses.
 The rationale for the avoidance of higher initial doses in most patients comes from several
small randomized trials that compared initial doses of 5 versus 10 mg of warfarin, which found
that higher doses generally did not result in more rapid therapeutic anticoagulation or
improved outcomes, but these higher doses were more likely to lead to a supratherapeutic
INR, which can increase the risk of bleeding.
 Additionally, there is a theoretical concern that higher initial doses might cause more
dramatic reductions in the anticoagulant factors protein S and protein C, leading to a
greater transient procoagulant state.
 For an adult who is frail, elderly (e.g., woman >70 years, man >80 years), malnourished, has
liver or kidney disease or heart failure, or is receiving a medication known to increase
warfarin sensitivity (e.g., amiodarone), we use a lower dose (e.g., 2.5 mg daily, 2.5 mg
alternating with 5 mg).
INR-based initial dose adjustment

 Typically, the PT/INR is measured daily in hospitalized patients and starting on or around
day 3 in healthy outpatients, and dosing on day 3 and subsequent days is based on the
PT/INR.