Prospective Genotyping For Total Hip or Knee Replacement Patients Receiving Warfarin (Coumadin)

Several human genes affect how medications are metabolized by the body. It is believed that knowledge of variations of these genes can help health care providers better manage an anticoagulation medicine called warfarin (Coumadin®)and as a result decrease patient problems with bleeding or the development of blood clots. This study is designed to evaluate if genetic testing can improve warfarin initiation better than usual care.

• Venous Thromboembolism
• Major Bleeding

• Genetic: Pharmacogenetic-based warfarin dosing

  Prior to elective joint replacement surgery a blood sample is collected for genetic information(genotyping)which will be used for calculating warfarin doses for patients randomized to the cytochrome arm. Outcomes in terms of efficacy, safety, and management of warfarin will be compared between this group and the group in which warfarin doses are determined per usual care.

  NOTE: Standard of care for elective knee and hip replacement at our institution is to receive post-operative warfarin thromboprophylaxis. Administration of warfarin is not specific to this study, nor is the duration of prophylaxis, however, warfarin dosing will be influenced by the study arm as noted above.

• Other: Usual care warfarin dosing

  For patients in arm 2, the control group, warfarin dosing is per usual care. Outcomes in terms of safety, efficacy, and warfarin management will be compared to that of patients in the other arm, who receive warfarin dosing based on genotyping.

  NOTE: Standard of care for elective knee and hip replacement at our institution is to receive post-operative warfarin thromboprophylaxis. Administration of warfarin is not specific to this study, nor is the duration of prophylaxis, however, warfarin dosing will be influenced by the study arm as noted above.

• Experimental: 1

  Pharmacogenetic-based warfarin dosing: Warfarin dosing based on formula that incorporates genetic testing results.

  NOTE: Standard of care for elective knee and hip replacement at our institution is to receive post-operative warfarin thromboprophylaxis. Administration of warfarin is not specific to this study, nor is the duration of prophylaxis, however, warfarin dosing will be influenced by the study arm, as noted above.

  Intervention: Genetic: Pharmacogenetic-based warfarin dosing
• Active Comparator: 2

  Control or "usual care" warfarin dosing

  NOTE: Standard of care for elective knee and hip replacement at our institution is to receive post-operative warfarin thromboprophylaxis. Administration of warfarin is not specific to this study, nor is the duration of prophylaxis, however, warfarin dosing will be influenced by the study arm, as noted above.

  Intervention: Other: Usual care warfarin dosing

Inclusion Criteria:

• Participants will be otherwise healthy adults (≥ 18 years of age) who are planning total hip or knee replacement or revision surgery at the University of Utah Hospital, and schedule a pre-operative office visit at the University of Utah Orthopaedic Center.

Exclusion Criteria:

• Blood transfusion in previous two weeks
• Participant is already taking warfarin
• Pre-operative INR > 4.0
• Pre-operative bilirubin > 2.4 mg/dL
• Current active cancer diagnosis with ongoing treatment
• Concomitant medications known to exert a major interaction with warfarin such as septra, metronidazole, tramadol, amiodarone, ciprofloxacin, or cimetidine.