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Review Article |

Preoperative or Postoperative Start of Prophylaxis for Venous Thromboembolism With Low-Molecular-Weight Heparin in Elective Hip Surgery? FREE

Niklaus Strebel, MD; Martin Prins, MD; Giancarlo Agnelli, MD; Harry R. Büller, MD
[+] Author Affiliations

From the Departments of Vascular Medicine (Drs Strebel and Büller) and Clinical Epidemiology and Biostatistics (Dr Prins), Academic Medical Center, Amsterdam, the Netherlands; and the Department of Medicine, Section of Internal and Cardiovascular Medicine, Universita di Perugia, Perugia, Italy (Dr Agnelli).


Arch Intern Med. 2002;162(13):1451-1456. doi:10.1001/archinte.162.13.1451.
Text Size: A A A
Published online

Background  Prophylaxis of venous thromboembolism with low-molecular-weight heparins in patients undergoing major orthopedic surgery is currently initiated according to at least 3 different regimens. In Europe, traditionally, prophylaxis is started 12 hours before surgery, whereas in North America it is initiated 12 to 48 hours postoperatively. The third regimen (perioperative) begins prophylaxis either earlier than 12 hours before or 12 hours after surgery. Unfortunately, the optimal regimen is uncertain because direct comparisons among these regimens with sufficiently large sample sizes are not available.

Objective  To assess, in a systematic review, the relative efficacy and safety of the 3 low-molecular-weight heparin regimens used to prevent thrombosis after total hip replacement. The incidence of postoperative thrombosis detected by contrast venography was used as the measure of efficacy and the rate of major bleeding was used as the measure of safety.

Methods  We pooled the results of all published studies, which met the following criteria: (1) inclusion of in at least 1 arm of the study of a dose of low-molecular-weight heparin that is approved for both preoperative and postoperative initiation of prophylaxis; (2) the use of mandatory bilateral contrast venography, performed between days 6 and 15 postoperatively; (3) thromboprophylaxis continued until venography; (4) independent reading of venograms; and (5) assessment of clinically overt major bleeding by predefined criteria. Articles were excluded if no separate data could be obtained for patients undergoing elective hip surgery (in case of patient mix), or if they were reported more than once.

Results  In the 1926 patients who used a preoperative regimen, the incidence of postoperative deep vein thrombosis was 19.2% (95% confidence interval [CI], 17%-21%). In the cohort of 925 patients who received a perioperative regimen, the rate of deep vein thrombosis was 12.4% (95% CI, 10%-14%), whereas in the group of 694 patients who received a postoperative regimen, it was 14.4% (95% CI, 12%-17%). The rate of major bleeding was 1.4% (95% CI, 1%-2%) in the preoperative group, 6.3% (95% CI, 5%-7%) in the perioperative group, and 2.5% (95% CI, 1%-3%) in the postoperative group.

Conclusions  We find no convincing evidence that starting prophylaxis preoperatively is associated with a lower incidence of venous thromboembolism than starting postoperatively. Perioperative regimens may lower the risk of postoperative thrombosis, but if so, this positive effect is offset by an increase in postoperative major bleeding.

MULTIPLE RANDOMIZED clinical trials have established that treatment with low-molecular-weight heparin (LMWH) is an effective and safe method for preventing venous thromboembolism after elective orthopedic surgery. It is believed that the surgical procedure itself (and the associated immobility) is the primary initiator of the thrombotic process. This notion of pathogenesis has led to the widely held European view that, to be optimally effective, prophylaxis should be initiated preoperatively. On the other hand, concerns about the risk of bleeding during surgery and the interference with regional anesthesia led to the North American approach of initiating LMWH after surgery. Therefore, for years, clinical practice relating to the time of initiation of prophylaxis has differed in Europe and North America. In the typical European regimen, prophylaxis is started 12 hours prior to surgery, whereas in North America, prophylaxis is usually started 12 to 24 hours after the operation. An alternative approach, which has recently been reinvestigated, is to start prophylaxis several hours before or shortly after surgery with adapted doses. All 3 regimens have been shown to be effective in preventing postoperative deep vein thrombosis (DVT), but there are no definitive data about the relative efficacy and safety of these 3 strategies.

In the absence of clinical trials with adequate sample sizes comparing the 3 regimens directly, we conducted a systematic review to assess the rate of venous thrombosis (as assessed by mandatory venography) and the occurrence of major hemorrhage with each of these LMWH regimens in patients undergoing elective hip surgery. Our aim was to determine whether starting prophylaxis prior to surgery is advantageous. To allow a fair comparison, we limited the analysis to studies using the same dose of LMWH preoperatively or postoperatively.

SEARCH STRATEGY

We searched for randomized controlled trials reporting on the incidence of venous thrombosis and bleeding in patients undergoing elective hip surgery with LMWH prophylaxis. Studies were identified through MEDLINE (Medical Subject Headings of the National Library of Medicine keywords: hip prosthesis, venous thrombosis, and low molecular weight heparins). The reference lists of the identified articles were then manually checked for additional publications.

ELIGIBILITY CRITERIA FOR STUDIES

Included in the systematic review were all trials that met the following criteria: (1) at least 1 arm of the study should have included a currently recommended dose of LMWH that is approved for both preoperative and postoperative initiation; (2) mandatory bilateral contrast venography, performed between days 6 and 15 postoperatively; (3) continuation of thromboprophylaxis until venography; (4) independent reading of venogram; and (5) assessment of clinically overt major bleeding by predefined criteria. Articles were excluded if separate data could not be obtained for patients undergoing elective hip surgery (in case of patient mix), or if they were reported more than once.

CLASSIFICATION OF THE PROPHYLACTIC REGIMENS

Studies were divided into 3 groups according to the time of the initiation of prophylaxis. Preoperative regimens had to start prophylaxis at least 12 hours before the operation, usually defined as the evening before surgery. The perioperative group included all trials that began prophylaxis 2 hours before or up to 4 hours after surgery. In the group using postoperative regimens, prophylaxis was started 12 to 48 hours after the surgical procedure.

OUTCOMES

Efficacy was assessed by the incidence of venographically documented DVT between 6 and 15 days postoperatively, or documented symptomatic DVT that occurred earlier. Safety was assessed by documenting the number of major bleeding episodes. No attempt was made to compare the frequency of minor bleeding because of the large variation in definitions used.

STATISTICAL ANALYSIS

The incidences of DVT and major bleeding were pooled for trials in each of the 3 regimens. Pooling was weighted based on sample size, and 95% confidence intervals (CIs) were calculated.

LITERATURE SEARCH AND TRIAL SELECTION

Of the 49 identified trials, 14 were not eligible (4 trials used doses of LMWH that are currently not recommended for preoperative and postoperative use;14) venography was not mandatory in 5 trials59; in 3 other studies, the time of venography was outside the 6- to 15-day postoperative window1012; in 1 trial, venography was only unilateral13; and in 1 study, bleeding was not systematically documented.14

Of the 35 potentially eligible studies, another 21 had to be excluded. Of these, 13 were published more than once,1527 6 studies investigated patients with hip and/or knee arthroplasty where the data could not be analyzed separately,2833 and 2 studies included patients with hip fractures.34,35 Thus, a total of 14 trials that reported on 19 cohorts of patients were included.3649

INCIDENCE OF POSTOPERATIVE DVT

Eleven trials were included for analysis of efficacy of the preoperative regimens; 9 with enoxaparin sodium, 1 with dalteparin sodium, and 1 with tinzaparin sodium (Table 1). Three studies were included for the perioperative regimen, 1 with enoxaparin and 2 with dalteparin, whereas 4 studies used a postoperative regimen, all using enoxaparin.

Table Graphic Jump LocationTable 1. Characteristics of the Studies Included in the Overview

The overall incidence of DVT, as well as that for proximal and distal DVT separately, for the study cohorts is presented in Table 2.

Table Graphic Jump LocationTable 2. Frequency of Venography-Detected Deep Vein Thrombosis and Incidence of Major Bleeding for the Various Low-Molecular-Weight Heparin Regimens*

In the preoperative group of trials, a total of 1926 patients (Table 3) were available with an incidence of thrombosis of 19.2% (95% CI, 17%-21%). The perioperative group included 925 patients (Table 3) and showed an incidence of postoperative DVT of 12.4% (95% CI, 10%-14%). In the postoperative group, a total of 694 patients were studied. The incidence of postoperative DVT was 14.4% (95% CI, 12%-17%). The incidence of proximal DVT was 7.6% for the preoperative group, 2% for the perioperative group, and 5% for the postoperative group. The majority of patients in both the preoperative and postoperative groups were treated with enoxaparin. If we limit the analysis to this LMWH only, the incidence of thrombosis for the preoperative group is 18% (95% CI, 16%-20%) and 14.4% (95% CI, 12%-17%) for the postoperative group (Table 2).

Table Graphic Jump LocationTable 3. Pooled Analysis of the Frequencies of Deep Vein Thrombosis and Major Bleeding Episodes of the 3 Low-Molecular-Weight Heparin Regimens*
INCIDENCE OF MAJOR BLEEDING

The incidence of major bleeding in each of the cohorts is summarized in Table 2. In the preoperative group (2785 patients), the incidence of major bleeding was 1.4% (95% CI, 1%-2%), in the perioperative group (1315 patients), the incidence was 6.3% (95% CI, 5%-7%), and in the postoperative group (751 patients) it was 2.5% (95% CI, 1%-3%) (Table 3).

The main conclusion of our pooled analysis across different studies with a preoperative, perioperative, or postoperative initiation of thromboprophylaxis with LMWH is that there is no convincing evidence that starting prophylaxis approximately 12 hours before surgery is more effective in preventing venography-detected DVT than starting 12 to 48 hours postoperatively (total DVT rate preoperatively and postoperatively; 19.2% [95% CI, 17%-21%] and 14.4% [95%CI, 12%-17%], respectively). Similarly, there is no evidence that the postoperative regimen is safer than the preoperative regimen. In contrast, when thromboprophylaxis is started either soon before (2 hours) or after (4 hours) surgery, even with reduced doses, there is a trend for a lower risk of venous thrombosis, but this benefit appears to be counterbalanced by a marked increase in the risk of major bleeding in comparison with the 2 other regimens (major bleeding rate was 6.3% [95% CI, 5%-7%] in the perioperative group compared with 1.4% [95% CI, 1%-2%] and 2.5% [95% CI, 1%-3%] in the preoperative and postoperative groups, respectively).

Since the across-study comparisons used in our analysis has obvious limitations, it is important to compare our findings with those of the few studies that have compared several regimens directly, as well as with an earlier overview on this topic. The only published study that compared a 12-hour preoperative regimen with a perioperative regimen (1 hour after induction of anesthesia) and a postoperative regimen (12 hours) was performed by Planes et al23—it found no statistical difference in efficacy. This study was performed to evaluate the safety of combining LMWH with various types of anesthesia and only about 60 patients were included in each of the 3 groups.

Recently, Hull and colleagues41 compared an early preoperative regimen (2 hours preoperatively) with an early postoperative regimen (4 hours postoperatively) with reduced doses of an LMWH (dalteparin, 2500 IU, 2 hours preoperatively, 4 hours postoperatively, respectively, followed by 5000 IU/d). There were about 300 patients in each group. The incidence of postoperative thrombosis was 11% in the group that started prophylaxis 2 hours preoperatively and 13% in the 4 hours postoperative group. This relatively low incidence of thrombosis is offset by a relatively high rate of major bleeding of 8.8% in the early preoperative group and 6.8% in the early postoperative group. The rates of bleeding in both of these perioperative groups are higher than those observed in our pooled postoperative and preoperative groups as well as in the 2 other perioperative groups reported by Planes et al23 and Francis et al.40 Comparisons of major bleeding in our analysis with the study reported by Hull et al41 are limited both because they are indirect and because they did not use identical definitions of major bleeding.

Our conclusions also differ from those reported in a meta-analysis published in 1999 in which the efficacy and safety of preoperative and postoperative initiation of a single LMWH was compared.50 This earlier meta-analysis concluded that the preoperative regimen was more effective and as safe as the postoperative regimen. The major differences between the 2 meta-analyses are that we included more studies, allowed the inclusion of different LMWHs, and did not exclude the large study by Eriksson et al.39 We limited our analysis to one and the same dose regimen used preoperatively and postoperatively so as not to introduce bias due to larger doses used postoperatively. If, however, we limit the analysis to the same LMWH that was studied in the other meta-analysis, our overall conclusions do not change.

The optimal timing for initiating postoperative thromboprophylaxis remains controversial. For example, the recent pentasaccharide study4 initiated prophylaxis subcutaneously 6 hours after surgery with a major reduction in the rate of venous thrombosis without an apparent increase in clinically important bleeding. In another dose-finding study with a compound directed against the tissue factor VIIa complex, prophylaxis using the subcutaneous route51 was started within 1 hour after surgery, without an apparent increase in major bleeding.

It is likely that with the increasing use of regional anesthesia, the preoperative initiation of thromboprophylaxis will gradually disappear and that future research will be directed toward the optimal timing of postoperative prophylaxis. It is also possible that the optimal timing might differ depending on the mechanism of action of the agent in question.

We conclude that for the currently used LMWHs, there is no convincing evidence that starting prophylaxis 12 hours preoperatively is associated with a lower risk of venous thrombosis than when prophylaxis is started 12 to 24 hours postoperatively. Perioperative thromboprophylactic regimens require further investigation before their role can be defined.

Accepted for publication December 6, 2001.

We highly appreciated the critical review of the manuscript by J. Hirsh, MD, Hamilton, Ontario.

Levine  MNHirsh  JGent  M  et al.  Prevention of deep vein thrombosis after elective hip surgery: a randomized trial comparing low molecular weight heparin with standard unfractionated heparin. Ann Intern Med. 1991;114545- 551
Link to Article
Ofosu  FALevine  MCraven  SDewar  LShafai  SBlajchman  MA Prophylactically equivalent doses of enoxaparin and unfractionated heparin inhibit in vivo coagulation to the same extent. Br J Haematol. 1992;82400- 405
Link to Article
Turpie  AG Enoxaparin prophylaxis in elective hip surgery. Acta Chir Scand Suppl. 1990;556103- 107
Turpie  AGGallus  ASHoek  JA A Synthetic pentasaccharide for the prevention of deep-vein thrombosis after total hip replacement. N Engl J Med. 2001;344619- 625
Link to Article
Torholm  CBroeng  LJorgensen  PS  et al.  Thromboprophylaxis by low-molecular-weight heparin in elective hip surgery: a placebo controlled study. J Bone Joint Surg Br. 1991;73434- 438
Kovacs  MJWeir  KMacKinnon  KKeeney  MBrien  WFCruickshank  MK Body weight does not predict for anti-Xa levels after fixed dose prophylaxis with enoxaparin after orthopedic surgery. Thromb Res. 1998;91137- 142
Link to Article
Avikainen  Vvon Bonsdorff  HPartio  E  et al.  Low molecular weight heparin (enoxaparin) compared with unfractionated heparin in prophylaxis of deep venous thrombosis and pulmonary embolism in patients undergoing hip replacement. Ann Chir Gynaecol. 1995;8485- 90
Rader  CPKramer  CKonig  AGohlke  FEulert  J Comparison between low-molecular and unfractionated heparin in the prevention of thrombosis in patients with total endoprosthetic replacement of hip and knee joint [in German]. Z Orthop Ihre Grenzgeb. 1997;13552- 57
Link to Article
Warwick  DBannister  GCGlew  D  et al.  Perioperative low-molecular-weight heparin: is it effective and safe? J Bone Joint Surg Br. 1995;77715- 719
Nilsson  PEBergqvist  DBenoni  G  et al.  The post-discharge prophylactic management of the orthopedic patient with low-molecular-weight heparin: enoxaparin. Orthopedics. 1997;20(suppl)22- 25
Bergqvist  DBenoni  GBjorgell  O  et al.  Low-molecular-weight heparin (enoxaparin) as prophylaxis against venous thromboembolism after total hip replacement. N Engl J Med. 1996;335696- 700
Link to Article
Lassen  MRBorris  LCAnderson  BS  et al.  Efficacy and safety of prolonged thromboprophylaxis with a low molecular weight heparin (dalteparin) after total hip arthroplasty—the Danish Prolonged Prophylaxis (DaPP) Study. Thromb Res. 1998;89281- 287
Link to Article
Warwick  DHarrison  JGlew  DMitchelmore  APeters  TJDonovan  J Comparison of the use of a foot pump with the use of low-molecular-weight heparin for the prevention of deep-vein thrombosis after total hip replacement: a prospective, randomized trial. J Bone Joint Surg Am. 1998;801158- 1166
Dahl  OEAndreassen  GAspelin  T  et al.  Prolonged thromboprophylaxis following hip replacement surgery—results of a double-blind, prospective, randomised, placebo-controlled study with dalteparin (Fragmin). Thromb Haemost. 1997;7726- 31
Bara  LPlanes  ASamama  MM Occurrence of thrombosis and haemorrhage, relationship with anti-Xa, anti-IIa activities, and D-dimer plasma levels in patients receiving a low molecular weight heparin, enoxaparin or tinzaparin, to prevent deep vein thrombosis after hip surgery. Br J Haematol. 1999;104230- 240
Link to Article
Colwell  CW  JrSpiro  TETrowbridge  AA  et al. for the Enoxaparin Clinical Trial Group, Use of enoxaparin, a low-molecular-weight heparin, and unfractionated heparin for the prevention of deep venous thrombosis after elective hip replacement: a clinical trial comparing efficacy and safety. J Bone Joint Surg Am. 1994;763- 14
Dahl  OEAspelin  TArnesen  H  et al.  Increased activation of coagulation and formation of late deep venous thrombosis following discontinuation of thromboprophylaxis after hip replacement surgery. Thromb Res. 1995;80299- 306
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Hull  RDPineo  GFFrancis  C  et al. for the North American Fragmin Trial Investigators, Low-molecular-weight heparin prophylaxis using dalteparin extended out-of-hospital vs in-hospital warfarin/out-of-hospital placebo in hip arthroplasty patients: a double-blind, randomized comparison. Arch Intern Med. 2000;1602208- 2215
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Planes  AVochelle  N The post-hospital discharge venous thrombosis risk of the orthopedic patient. Orthopedics. 1997;20(suppl)18- 21
Planes  AVochelle  NDarmon  JY  et al.  Efficacy and safety of postdischarge administration of enoxaparin in the prevention of deep venous thrombosis after total hip replacement: a prospective randomised double-blind placebo-controlled trial. Drugs. 1996;5247- 54
Link to Article
Planes  AVochelle  NDarmon  JYFagola  MBellaud  MHuet  Y Risk of deep-venous thrombosis after hospital discharge in patients having undergone total hip replacement: double-blind randomised comparison of enoxaparin versus placebo. Lancet. 1996;348224- 228
Link to Article
Planes  AVochelle  NFagola  MBellaud  Mfor the Reviparin Study Group, Comparison of two low-molecular-weight heparins for the prevention of postoperative venous thromboembolism after elective hip surgery. Blood Coagul Fibrinolysis. 1998;9499- 505
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Planes  AVochelle  NFagola  M  et al.  Efficacy and safety of a perioperative enoxaparin regimen in total hip replacement under various anesthesias. Am J Surg. 1991;161525- 531
Link to Article
Planes  AVochelle  NMazas  F  et al.  Double-blind randomized comparative study of enoxaparin and standard heparin in the prevention of thromboembolic disease during insertion of total hip replacement [in French]. Rev Med Interne. 1988;9327- 333
Link to Article
Planes  AVochelle  NMazas  F  et al.  The use of enoxaparine in preventing deep venous thrombosis following total hip prosthesis: randomized multicenter prospective trial [in French]. Rev Chir Orthop Reparatrice Appar Mot. 1988;74215- 218
Turpie  AG Efficacy of a postoperative regimen of enoxaparin in deep vein thrombosis prophylaxis. Am J Surg. 1991;161532- 536
Link to Article
Turpie  AGLevine  MNHirsh  J  et al.  A randomized controlled trial of a low-molecular-weight heparin (enoxaparin) to prevent deep-vein thrombosis in patients undergoing elective hip surgery. N Engl J Med. 1986;315925- 929
Link to Article
Della Valle  CJJazrawi  LMIdjadi  J  et al.  Anticoagulant treatment of thromboembolism with intravenous heparin therapy in the early postoperative period following total joint arthroplasty. J Bone Joint Surg Am. 2000;82207- 212
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Leclerc  JRGent  MHirsh  JGeerts  WHGinsberg  JSfor the Canadian Collaborative Group, The incidence of symptomatic venous thromboembolism during and after prophylaxis with enoxaparin: a multi-institutional cohort study of patients who underwent hip or knee arthroplasty. Arch Intern Med. 1998;158873- 878
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Shaieb  MDWatson  BNAtkinson  RE Bleeding complications with enoxaparin for deep venous thrombosis prophylaxis. J Arthroplasty. 1999;14432- 438
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Barsotti  JGruel  YRosset  P  et al.  Comparative double-blind study of two dosage regimens of low-molecular weight heparin in elderly patients with a fracture of the neck of the femur. J Orthop Trauma. 1990;4371- 375
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Magnusson  MEriksson  BIKalebo  PSivertsson  R Is colour Doppler ultrasound a sensitive screening method in diagnosing deep vein thrombosis after hip surgery? Thromb Haemost. 1996;75242- 245
Boris  LHauch  OJorgensen  LHansen  Bfor the Danish Enoxaparin Study Group, Low-molecular-weight heparin (enoxaparin) vs dextran 70: the prevention of postoperative deep vein thrombosis after total hip replacement. Arch Intern Med. 1991;1511621- 1624
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Colwell  CW  JrSpiro  TE Efficacy and safety of enoxaparin to prevent deep vein thrombosis after hip arthroplasty. Clin Orthop. 1995;(319)215- 222
Eriksson  BIKalebo  PAnthymyr  BAWadenvik  HTengborn  LRisberg  B Prevention of deep-vein thrombosis and pulmonary embolism after total hip replacement: comparison of low-molecular-weight heparin and unfractionated heparin. J Bone Joint Surg Am. 1991;73484- 493
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Hull  RDPineo  GFFrancis  C  et al. for the North American Fragmin Trial Investigators, Low-molecular-weight heparin prophylaxis using dalteparin in close proximity to surgery vs warfarin in hip arthroplasty patients: a double-blind, randomized comparison. Arch Intern Med. 2000;1602199- 2207
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Kalodiki  EPHoppensteadt  DANicolaides  AN  et al.  Deep venous thrombosis prophylaxis with low molecular weight heparin and elastic compression in patients having total hip replacement: a randomised controlled trial. Int Angiol. 1996;15162- 168
Planes  A Comparison of antithrombotic efficacy and haemorrhagic side-effects of clivarin versus enoxaparin in patients undergoing total hip replacement surgery. Blood Coagul Fibrinolysis. 1993;4(suppl 1)S33- S38
Planes  ASamama  MMLensing  AW  et al.  Prevention of deep vein thrombosis after hip replacement—comparison between two low-molecular heparins, tinzaparin and enoxaparin. Thromb Haemost. 1999;8122- 25
Planes  AVochelle  NFagola  M  et al.  Once-daily dosing of enoxaparin (a low molecular weight heparin) in prevention of deep vein thrombosis after total hip replacement. Acta Chir Scand Suppl. 1990;556108- 115
Planes  AVochelle  NFagola  MFeret  JBellaud  M Prevention of deep vein thrombosis after total hip replacement: the effect of low-molecular-weight heparin with spinal and general anaesthesia. J Bone Joint Surg Br. 1991;73418- 422
Planes  AVochelle  NMazas  F  et al.  Prevention of postoperative venous thrombosis: a randomized trial comparing unfractionated heparin with low molecular weight heparin in patients undergoing total hip replacement. Thromb Haemost. 1988;60407- 410
Samama  CMClergue  FBarre  JMontefiore  AIll  PSamii  Kfor the Arar Study Group, Low molecular weight heparin associated with spinal anaesthesia and gradual compression stockings in total hip replacement surgery. Br J Anaesth. 1997;78660- 665
Link to Article
Spiro  TEJohnson  GJChristie  MJ  et al. for the Enoxaparin Clinical Trial Group, Efficacy and safety of enoxaparin to prevent deep venous thrombosis after hip replacement surgery. Ann Intern Med. 1994;12181- 89
Link to Article
Hull  RDBrant  RFPineo  GFStein  PDRaskob  GEValentine  KA Preoperative vs postoperative initiation of low-molecular-weight heparin prophylaxis against venous thromboembolism in patients undergoing elective hip replacement. Arch Intern Med. 1999;159137- 141
Link to Article
Lee  AAgnelli  GBüller  H  et al.  A dose-response study of the factor VIIa/ tissue factor inhibitor rNAPc2 in the prevention of postoperative venous thrombosis in patients undergoing total knee arthroplasty. Blood. 2000;96491

Figures

Tables

Table Graphic Jump LocationTable 1. Characteristics of the Studies Included in the Overview
Table Graphic Jump LocationTable 2. Frequency of Venography-Detected Deep Vein Thrombosis and Incidence of Major Bleeding for the Various Low-Molecular-Weight Heparin Regimens*
Table Graphic Jump LocationTable 3. Pooled Analysis of the Frequencies of Deep Vein Thrombosis and Major Bleeding Episodes of the 3 Low-Molecular-Weight Heparin Regimens*

References

Levine  MNHirsh  JGent  M  et al.  Prevention of deep vein thrombosis after elective hip surgery: a randomized trial comparing low molecular weight heparin with standard unfractionated heparin. Ann Intern Med. 1991;114545- 551
Link to Article
Ofosu  FALevine  MCraven  SDewar  LShafai  SBlajchman  MA Prophylactically equivalent doses of enoxaparin and unfractionated heparin inhibit in vivo coagulation to the same extent. Br J Haematol. 1992;82400- 405
Link to Article
Turpie  AG Enoxaparin prophylaxis in elective hip surgery. Acta Chir Scand Suppl. 1990;556103- 107
Turpie  AGGallus  ASHoek  JA A Synthetic pentasaccharide for the prevention of deep-vein thrombosis after total hip replacement. N Engl J Med. 2001;344619- 625
Link to Article
Torholm  CBroeng  LJorgensen  PS  et al.  Thromboprophylaxis by low-molecular-weight heparin in elective hip surgery: a placebo controlled study. J Bone Joint Surg Br. 1991;73434- 438
Kovacs  MJWeir  KMacKinnon  KKeeney  MBrien  WFCruickshank  MK Body weight does not predict for anti-Xa levels after fixed dose prophylaxis with enoxaparin after orthopedic surgery. Thromb Res. 1998;91137- 142
Link to Article
Avikainen  Vvon Bonsdorff  HPartio  E  et al.  Low molecular weight heparin (enoxaparin) compared with unfractionated heparin in prophylaxis of deep venous thrombosis and pulmonary embolism in patients undergoing hip replacement. Ann Chir Gynaecol. 1995;8485- 90
Rader  CPKramer  CKonig  AGohlke  FEulert  J Comparison between low-molecular and unfractionated heparin in the prevention of thrombosis in patients with total endoprosthetic replacement of hip and knee joint [in German]. Z Orthop Ihre Grenzgeb. 1997;13552- 57
Link to Article
Warwick  DBannister  GCGlew  D  et al.  Perioperative low-molecular-weight heparin: is it effective and safe? J Bone Joint Surg Br. 1995;77715- 719
Nilsson  PEBergqvist  DBenoni  G  et al.  The post-discharge prophylactic management of the orthopedic patient with low-molecular-weight heparin: enoxaparin. Orthopedics. 1997;20(suppl)22- 25
Bergqvist  DBenoni  GBjorgell  O  et al.  Low-molecular-weight heparin (enoxaparin) as prophylaxis against venous thromboembolism after total hip replacement. N Engl J Med. 1996;335696- 700
Link to Article
Lassen  MRBorris  LCAnderson  BS  et al.  Efficacy and safety of prolonged thromboprophylaxis with a low molecular weight heparin (dalteparin) after total hip arthroplasty—the Danish Prolonged Prophylaxis (DaPP) Study. Thromb Res. 1998;89281- 287
Link to Article
Warwick  DHarrison  JGlew  DMitchelmore  APeters  TJDonovan  J Comparison of the use of a foot pump with the use of low-molecular-weight heparin for the prevention of deep-vein thrombosis after total hip replacement: a prospective, randomized trial. J Bone Joint Surg Am. 1998;801158- 1166
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