Evaluation of Maintenance Dosing vs Loading Dosing Upon Restarting Warfarin Therapy: A Prospective Randomized Trial

• re-starting warfarin "loading" dose vs "maintenance" dose [ Time Frame: INR drawn 3 days post-reinitiation and then every 2 days until therapeutic ] [ Designated as safety issue: Yes ]
  To compare the time taken to achieve a therapeutic INR between those patients re-starting warfarin with a "loading" dose and a "maintenance" dosing regimen using linear interpolation of INRs.
  
  

• Compare % of time within, above and below the target INR range [ Time Frame: days ] [ Designated as safety issue: No ]
  To compare the % of time within, above and below the desired INR range between those patients re-starting warfarin with a "loading" dose or "maintenance" dose 6 weeks following restarting warfarin.
  
  
• Compare bleeding/clotting complications between two groups [ Time Frame: 30 days, 90 days ] [ Designated as safety issue: No ]
  To compare the rates of thrombosis (i.e., stroke) / major hemorrhage between those re-starting warfarin with a "loading" dose or "maintenance" dose at 30 days and 90 days following restarting warfarin.
  
  
• Compare the levels of protein C, protein S, and factor II between 2 groups. [ Time Frame: week ] [ Designated as safety issue: No ]
  To compare the levels of protein C, protein S, and factor II between those re-starting warfarin with a "loading" dose or "maintenance" dose.
  
  

Patients will be identified via the University of Alberta Hospital Anticoagulation Management Service. Following the receipt of written, informed consent, patients will be randomized to re-start warfarin at their "maintenance" dose or at a "loading" dose (1.5 times the maintenance dose for 3 days, then resumption of warfarin dosing as per the maintenance dose). Randomization will be performed on-line through the EPICORE Centre.

Assuming Day 1 is the day warfarin is re-started, patients will have INRs done on day 3 and at least every 2 days thereafter until a therapeutic INR is obtained. In addition, protein C, protein S and factor II levels will be obtained while the patient is on stable maintenance dosing of warfarin (i.e., prior to holding warfarin for the procedure), 7 days after re-starting warfarin, and 14 days after re-starting warfarin. Complete blood counts (CBCs) will be done with each INR if the patient is taking a low molecular weight heparin (LMWH). Patients will have their anticoagulant therapy managed by the AMS for 6 weeks and will receive a telephone follow-up by the AMS at 90 days to determine if any bleeding or clotting complications occurred.