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Timing of Initial Administration of Low-Molecular-Weight Heparin Prophylaxis Against Deep Vein Thrombosis in Patients Following Elective Hip Arthroplasty
A Systematic Review
Russell D. Hull, MBBS;
Graham F. Pineo, MD;
Paul D. Stein, MD;
Andrew F. Mah, BSc;
Susan M. MacIsaac, MSc;
Ola E. Dahl, MD, PhD;
William A. Ghali, MD, MPH;
Matthew S. Butcher, BSc;
Rollin F. Brant, PhD;
David Bergqvist, MD, PhD;
Karly Hamulyák, MD;
Charles W. Francis, MD;
Victor J. Marder, MD;
Gary E. Raskob, PhD
Arch Intern Med. 2001;161:1952-1960.
Background Perioperative and postoperative venous thrombosis are common in patients
undergoing elective hip surgery. Prophylactic regimens include subcutaneous
low-molecular-weight heparin 12 hours or more before or after surgery and
oral anticoagulants. Recent clinical trials suggest that low-molecular-weight
heparin initiated in closer proximity to surgery is more effective than the
present clinical practice. We performed a systematic review of the literature
to assess the efficacy and safety of low-molecular-weight heparin administered
at different times in relation to surgery vs oral anticoagulant prophylaxis.
Methods Reviewers (A.F.M. and S.M.M.) identified studies by searching MEDLINE,
reviewing references from retrieved articles, scanning abstracts from conference
proceedings, and contacting investigators and pharmaceutical companies. Randomized
trials comparing low-molecular-weight heparin administered at different times
relative to surgery with oral anticoagulants in patients undergoing elective
hip arthroplasty, evaluated using contrast phlebography, were selected. Two
reviewers (A.F.M. and S.M.M.) extracted data independently.
Results The literature review identified 4 randomized trials meeting predefined
inclusion criteria. The results indicate that low-molecular-weight heparin
initiated in close proximity to surgery resulted in absolute risk reductions
of 11% to 13% for deep vein thrombosis, corresponding to relative risk reductions
of 43% to 55% compared with oral anticoagulants. Low-molecular-weight heparin
initiated 12 hours before surgery or 12 to 24 hours postoperatively was not
more effective than oral anticoagulants. Low-molecular-weight heparin initiated
postoperatively in close proximity to surgery at half the usual dose was not
associated with a clinically or statistically significant increase in major
bleeding rates (P = .16).
Conclusions The timing of initiating low-molecular-weight heparin significantly
influences antithrombotic effectiveness. The practice of delayed initiation
of low-molecular-weight heparin prophylaxis results in suboptimal antithrombotic
effectiveness without a substantive safety advantage.
From the Thrombosis Research Unit (Drs Hull, Pineo, and Brant; and
the Department of Medicine (Dr Ghali), University of Calgary, Calgary, Alberta;
St Joseph Mercy Oakland, Pontiac, Mich; the Research Forum, Department of
Orthopaedics, Ullevaal University Hospital, Oslo, Norway (Dr Dahl); Uppsala
University, Uppsala, Sweden (Dr Bergqvist); the Department of Haemotology,
University Hospital Maastricht, Maastricht, the Netherlands (Dr Hamulyák);
the Vascular Medicine Unit, University of Rochester Medical Center, Rochester,
NY; Vascular Medicine Program, Los Angeles Orthopaedic Hospital/University
of California, Los Angeles (Dr Marder); and the University of Oklahoma Health
Sciences Center, Oklahoma City (Dr Raskob).
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