Abstract

BackgroundDeep vein thrombosis (DVT) and pulmonary emboli (PE), known together as venous thromboembolic (VTE) disease remain major complications following elective hip and knee surgery. This study compares three chemoprophylactic regimens for VTE following elective primary unilateral hip or knee replacement, one of which was designed to minimize risk of post-operative bleeding.MethodsPatients were randomized and stratified for hip vs. knee to receive A: variable dose warfarin (first dose on the night preceding surgery with subsequent target INR 2.0–2.5), B: 2.5 mg fondaparinux daily starting 6–18 h postoperatively, or C: fixed 1.0 mg dose warfarin daily starting 7 days preoperatively. All treatments continued until bilateral leg venous ultrasound day 28 ± 2 or earlier upon a VTE event. The study examined primary endpoints including leg DVT, PE or death due to VTE and secondary endpoints including effects on D-dimer, estimated blood loss (EBL) at surgery and hemorrhagic complications.ResultsThree hundred fifty-five patients were randomized. None was lost to follow-up. Taking 1.0 mg warfarin for seven days preoperatively did not prolong the prothrombin time (PT). Two patients in Arm C had asymptomatic distal DVT. One major bleed occurred in Arm B and one in Arm C (ischemic colitis). Elevated d-dimer did not predict delayed VTE for one year.ConclusionsFixed low dose warfarin started preoperatively is equivalent to two other standards of care under study (95 % CI: -0.0428, 0.0067 for both) as VTE prophylaxis for the patients having elective major joint replacement surgery.Trial registrationClinicalTrials.gov identifier # NCT00767559FDA IND: 103,716

Highlights

  • Deep vein thrombosis (DVT) and pulmonary emboli (PE), known together as venous thromboembolic (VTE) disease remain major complications following elective hip and knee surgery

  • Warfarin when given at 1 mg per day is known to increase serum under-gamma-carboxylated osteocalcin and plasma under-gamma-carboxylated prothrombin, without change of prothrombin times or factor VII activity [15]. It is critical in this pharmacologic format that low dose warfarin be initiated prior to the surgical trauma, allowing time for warfarin to partially suppress the carboxylation of glutamic acid residues attached to the cores of factors II, VII, IX and X [16]

  • This study is a continuum of studies predicated upon the concept that the clotting system can be kept in a homeostatic balance, making it possible to avoid added risk of bleeding while protecting patients from thromboembolism [1,2,3,4,5,6,7,8,9,10,11,12,13,14]

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Summary

Introduction

Deep vein thrombosis (DVT) and pulmonary emboli (PE), known together as venous thromboembolic (VTE) disease remain major complications following elective hip and knee surgery. This study is a continuum of studies predicated upon the concept that the clotting system can be kept in a homeostatic balance, making it possible to avoid added risk of bleeding while protecting patients from thromboembolism [1,2,3,4,5,6,7,8,9,10,11,12,13,14] Among these studies was a prospective pilot study of 100 patients in which patients planning total hip replacement were randomized between two arms, one with warfarin starting with 5.0 mg the night prior to surgery followed by variable dose warfarin (target PT 1.3–1.5 x normal) and the other using 1.0 mg of warfarin beginning seven days prior to surgery, and both continuing for 30–45 days. Of 1,003 patients, only 3 (0.3 %) had symptomatic VTE [11]

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