Heparins and mechanical methods for thromboprophylaxis in ...

Heparins and mechanical methods for thromboprophylaxis incolorectal surgery (Review)Wille-Jørgensen P, Rasmussen MS, Andersen BR, Borly LThis is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library2006, Issue 2http://www.thecochranelibrary.comHeparins and mechanical methods for thromboprophylaxis in colorectal surgery (Review)Copyright © 2006 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd1

Analysis 05.02. Comparison 05 Thromboembolic events (TE). LMWH vs. placebo, Outcome 02 PE, no studies . .Analysis 05.03. Comparison 05 Thromboembolic events (TE). LMWH vs. placebo, Outcome 03 DVT and/or PE.Same as in “DVT”. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Analysis 06.01. Comparison 06 Thromboembolic events (TE). LMWH vs. no treatment or placebo, Outcome 01 DVTAnalysis 06.02. Comparison 06 Thromboembolic events (TE). LMWH vs. no treatment or placebo, Outcome 02 PE,same as LMWH versus no treatment . . . . . . . . . . . . . . . . . . . . . . . . . .Analysis 06.03. Comparison 06 Thromboembolic events (TE). LMWH vs. no treatment or placebo, Outcome 03 DVTand/or PE, same as LMWH versus no treatment or placebo / DVT . . . . . . . . . . . . . . .Analysis 07.01. Comparison 07 Thromboembolic events (TE). LDH or LMWH vs. no treatment or placebo, Outcome01 DVT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Analysis 07.02. Comparison 07 Thromboembolic events (TE). LDH or LMWH vs. no treatment or placebo, Outcome02 PE . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Analysis 07.03. Comparison 07 Thromboembolic events (TE). LDH or LMWH vs. no treatment or placebo, Outcome03 DVT and/or PE. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Analysis 08.01. Comparison 08 Thromboembolic events (TE). LDH vs. LMWH, Outcome 01 DVT . . . . .Analysis 08.02. Comparison 08 Thromboembolic events (TE). LDH vs. LMWH, Outcome 02 PE . . . . . .Analysis 08.03. Comparison 08 Thromboembolic events (TE). LDH vs. LMWH, Outcome 03 DVT and PE. . .Analysis 09.01. Comparison 09 Thromboembolic events (TE). LDH versus IPC, Outcome 01 DVT . . . . . .Analysis 09.02. Comparison 09 Thromboembolic events (TE). LDH versus IPC, Outcome 02 PE, no studies . . .Analysis 09.03. Comparison 09 Thromboembolic events (TE). LDH versus IPC, Outcome 03 DVT and/or PE. Same asin “DVT”. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Analysis 10.01. Comparison 10 Thromboembolic events (TE). LDH vs. LDH+TED, Outcome 01 DVT . . . .Analysis 10.02. Comparison 10 Thromboembolic events (TE). LDH vs. LDH+TED, Outcome 02 PE . . . . .Analysis 10.03. Comparison 10 Thromboembolic events (TE). LDH vs. LDH+TED, Outcome 03 DVT and/or PE.Analysis 11.01. Comparison 11 Thromboembolic events (TE). LDH vs. TED + IPC, Outcome 01 DVT . . . .Analysis 11.02. Comparison 11 Thromboembolic events (TE). LDH vs. TED + IPC, Outcome 02 PE, no studies .Analysis 11.03. Comparison 11 Thromboembolic events (TE). LDH vs. TED + IPC, Outcome 03 DVT and/or PE.Same as in “DVT”. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Analysis 12.01. Comparison 12 Thromboembolic events (TE). IPC vs. no treatment, Outcome 01 DVT . . . .Analysis 12.02. Comparison 12 Thromboembolic events (TE). IPC vs. no treatment, Outcome 02 PE, no studies .Analysis 12.03. Comparison 12 Thromboembolic events (TE). IPC vs. no treatment, Outcome 03 DVT and/or PE.Same as in “DVT”. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2828292930303131323233333434343535363636373737Heparins and mechanical methods for thromboprophylaxis in colorectal surgery (Review)Copyright © 2006 The Cochrane Collaboration. Published by John Wiley & Sons, Ltdii

Heparins and mechanical methods for thromboprophylaxis incolorectal surgery (Review)Wille-Jørgensen P, Rasmussen MS, Andersen BR, Borly LThis record should be cited as:Wille-Jørgensen P, Rasmussen MS, Andersen BR, Borly L. Heparins and mechanical methods for thromboprophylaxis in colorectalsurgery. The Cochrane Database of Systematic Reviews 2004, Issue 1. Art. No.: CD001217. DOI: 10.1002/14651858.CD001217.This version first published online: 26 January 2004 in Issue 1, 2004.Date of most recent substantive amendment: 28 August 2003A B S T R A C TBackgroundColorectal surgery implies higher risk of postoperative thromboembolic complications as deep venous thrombosis (DVT) and pulmonaryembolism (PE) than general surgery. The best prophylaxis in general surgery is heparin and graded compression stockings. No systematicreview on combination prophylaxis or on thrombosis prophylaxis in colorectal surgery has been published.ObjectivesTo compare the incidence of postoperative thromboembolism after colorectal surgery using prophylactic methods focussing on heparinsand mechanical methods alone and in combinations.Search strategyElectronic searches was performed in PUBMED, EMBASE, LILACS and the Cochrane Library. Abstract books from major congresseswere handsearched as were reference lists from previously performed reviews.Selection criteriaRCT or CCT comparing prophylactic interventions and/or placebo. Outcomes were ascending venography, 125 I-fibrinogen uptaketest, ultrasound methods, pulmonary scintigraphy. Studies, using thermographic methods, other isotopic methods, plethysmographicmethods, and purely clinical methods as the only diagnostic measure were excluded. 558 studies were identified - 477 were excluded.Only 3 of the identified studies focused exclusively on colorectal surgery. Studies of general surgery contain considerable numbers ofcolorectal patients. The authors of 66 studies in general and/or abdominal surgery were contacted for retrieving the results from thecolorectal patients. Answers were received from very few. 19 studies entered this review.Data collection and analysisAll studies and all data extraction were performed by at least two of the authors. Outcome was deep venous thrombosis and/or pulmonaryembolism. Analysis of bleeding complications were unfeasible. 12 meaningful outcomes were analysed by means of the fixed effectsmodel with Peto Odds Ratios.Main resultsHeparins versus no treatment: Any kind of heparincompared to no treatment or placebo (comparison 07.03, 11 studies). Heparin isbetter in preventing DVT and/or PE with a Peto Odds ratio at 0.32 (95% Confidence Interval 0.20-0.53)Unfractionated heparin versus low molecular weight heparin (comparison 08.03, 4 studies). The two treatments were found equallyeffective in preventing DVT and/or PE with a Peto Odds ratio 1.01 (95% Confidence Interval 0.67-1.52).Mechanical methods (comparison 10.3, 2 studies).The combination of graded compression stockings and LDH is better than LDHalone in preventing DVT and/or PE with a Peto Odds ratio at 4.17 (95% Confidence Interval 1.37-12.70).Authors’ conclusionsThe optimal prophylaxis in colorectal surgery is the combination of graduated compression stockings and low-dose unfractionatedheparin. The unfractionated heparin can be replaced with low molecular weight heparin.Heparins and mechanical methods for thromboprophylaxis in colorectal surgery (Review)Copyright © 2006 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd1

P L A I N L A N G U A G E S U M M A R YA combination of graduated compression stockings and heparin seems to be the optimal prophylaxis for patients undergoing colorectalsurgery.Patients undergoing surgery of the large bowel and the rectum have a considerable risk of developing vascular complications expressedas venous thrombosis and/or thrombosis in the lungs (pulmonary embolism). These complications can lead to lifelong impaired venousfunction in the legs or occasionally sudden postoperative death. In order to avoid these complications, patients are often treated withblood-thinning medicine (anticoagulation) and graded compression stockings during operation. A combination treatment of Heparinand TED-stockings have been proved effective in general surgery. This review demonstrates that this combined treatment also is effectivewithin the high-risk group of patients undergoing surgery of the large bowel or rectum.B A C K G R O U N DColorectal surgery implies a specific high risk for postoperativethromboembolic complications (TE) in form of deep venousthrombosis (DVT) and pulmonary embolism (PE) as comparedto general surgery (Wille-Jørgensen 1988, Torngren 1982, Wille-Jørgensen 1990, Kjaergaard 1985). The reason for this is unknown.Pelvic dissection and/ or the peroperative positioning ofthe patients has been suggested. The different types of prophylaxishave been very well documented both in respect of many RCT´ sand in systematic and unsystematic reviews (Collins et al 1988,Clagett 1988, Wille-Jørgensen 1991, Leizorovicz 1992, Nurmohammed1992, Jørgensen 1993, Clagett 1995). Most of these reviewshave dealt with the efficacy of various forms of heparin,and the overall conclusions are that low molecular weight heparin(LMWH) is an effective form of prophylaxis and perhaps betterthan unfractionated heparin. The latter question is addressed ina current Cochrane Review Protocol (Leizorovicz 1997). One investigationindicates, that a better prophylaxis can be obtained inpatients with malignant disease, using a higher dose of LMWH(Bergqvist 1995). Mechanical compression in forms of gradedcompression stockings and/or intermittent compression devicesare effective (Wille-Jørgensen 1991), and a systematic CochraneReview on the efficacy of graded compression stockings in all kindof surgery has recently been included in The Cochrane Library(Amarigiri 2000). A better prophylaxis can be obtained by the useof a combination of medical and mechanical prophylaxis (Wille-Jørgensen 1991). The use of this combination has not yet beensubject to a systematic review as well as a systematic review neverpreviously addressed the problems with thromboprophylaxis inthe group of patients undergoing colorectal surgery.O B J E C T I V E STo compare the incidence of postoperative thromboembolism aftercolorectal surgery having used different prophylactic methodsfocussing on various heparins and heparanoids and mechanicalmethods and their combinations.It was the plan to stratify the studies in pre- or postoperative startof prophylaxis, but due to few studies this was not possible.C R I T E R I A F O R C O N S I D E R I N GS T U D I E S F O R T H I S R E V I E WTypes of studiesRCT or CCT comparing minimum two of the mentioned prophylacticinterventions and/or placebo. The randomizations shouldhave taken place before start of treatment. As diagnostic measuresascending venography, 125 I-fibrinogen uptake test, ultrasound/doppler methods, pulmonary scintigraphy, or autopsy should havebeen used for the whole population. Studies, using thermographicmethods, other isotopic methods than the 125 I-fibrinogen uptaketest, plethysmographic methods, and purely clinical methodsas the only diagnostic measure have been excluded.As expected only few of the identified studies exclusively focusedon colorectal surgery. On the other hand most of the studies ingeneral surgery contain a considerable number of patients havingcolorectal surgery performed. The primary authors and/or thesponsoring pharmaceutical companies of studies in general and/orabdominal surgery were contacted in order to make them reportthe results from the colorectal patients exclusively.The start and end (in time) of the prophylaxis must have beenstatedThe studies should have described the mortality within 30 days.If this information is not available, it was sought directly fromauthors, but was very seldom obtained.Types of participantsPatients undergoing major colorectal surgery for cancer or benigndiseases. The participants had to be over 18 years of age. Majorsurgery implied:Resections with or without anastomosis, diverting stomas. Excludedwere endoscopic and/or transanal procedures.Types of interventionA: Unfractionated heparin (5000 IU b.i.d. or t.i.d)Heparins and mechanical methods for thromboprophylaxis in colorectal surgery (Review)Copyright © 2006 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd2

B: Low-molecular weight heparins in different dosesC: Any kind of heparin + graded compression stockingsD: Any kind of heparin + Intermittent pneumatic compressionE: Intermittent compression aloneF: Placebo or untreatedThe comparisons are listed in the tables of comparisons sectionTypes of outcome measuresThe outcome was either DVT, PE, fatal PE or total mortality,evaluated within a standardized postoperative time (preferably 30days for mortality and 7-14 days for DVT/PE).The TE were diagnosed in an objective way using either mandatoryvenography, 125I-fibrinogen-uptake test, or Doppler-ultrasound,pulmonary perfusion/ventilation scans and/or autopsy.The evaluations of the outcomes should at least be blinded againstthe prophylactic treatment given (assessor-blinding), if a doubleblindmethod was not used.It was the intention to include both intention to treat analyses andfulfilled protocol analysis. Due to the collected data, we were onlyable to perform the latter.S E A R C H M E T H O D S F O RI D E N T I F I C A T I O N O F S T U D I E SSee: Colorectal Cancer Group methods used in reviews.See: Collaborative review group search strategy:Electronic searches goes back to 1966 (in PUBMED, 1967 inLILACS and 1980 in EMBASE). The general search strategy,described by the Cochrane Colorectal Cancer Group was used inMEDLINE and The Cochrane Library as well as a comparablesearch strategy in EMBASE-search. A search for randomisedclinical trials (RCT) and controlled clinical trials (CCT) wasdone. The specialised search used the terms:colorectal orcolonic orrectal orgeneral surgery orabdominal surgeryandthrombos* or thromboem*andprophylaxis or preventionThe electronic searches searched up to May 2003.In order to identify more studies, the personal bibliographicregister belonging to Peer Wille-Jørgensen, Denmark, washand searched. The reference-lists form major review articlesfrom 1990 were scrutinized. All references from previouslyperformed meta-analyses were crossed-checked with the othersearches . The abstract books of the Congresses arranged by TheInternational Society on Thrombosis and Haemostasis as well asThe Mediterrenean League aganist Thrombosis were consultedback to 1976.M E T H O D S O F T H E R E V I E WAll identified trials were reviewed independently by two authors inorder to validate the scientific approach and to evaluate, whetherthe trial could be included. Following data were extracted byminimum two authors: Type of prophylaxis, type of endpoint(DVT, PE, TE, and fatal PE), bleeding listed as major and minorbleeding events, bleeding in ml, per- and postoperative transfusionrequirements. The definition of major and minor bleeding eventsfollowed the individual authors.If both authors disagreed on study-validity and/or data extractionconsensus was obtained. This happened in two occasions. Thebleeding episodes were so inhomogeneous described that it wasnot possible to relate these complications to the colorectal patients.An analysis of bleeding exclusively on colorectal patients was thusomitted.The authors of trials on general surgery were contacted by “snailmail”and E-mail (if possible) in order to stratify their individualtrial results in colorectal surgery and other surgery.Following pharmaceutical companies were asked for the colorectaldata from the studies on general surgery and abdominal surgery.- Leo Chemicals (Denmark) (tinzaparine)- Pharmacia (Sweden) (dalteparine)- Aventis (France, USA) (enoxaparine)- Choay (France) (fraxiparine)- Alfa (Italy) (Fluxum)- Knoll (Germany) (reviparine)The process of getting the colorectal data out of the studiesdescribing general surgery was extremely slow with a very modestoutcome. It was thus decided to finish the review with the resultsobtained. Studies from which the results after colorectal surgerycould not be obtained were not excluded, but placed in thecategory: Studies awaiting assessment, giving the authors an extrachance to answer our requests.The results from each trial were entered into the RevMan 4.1module and analysed as binomial data for the thromboembolicendpoints. We used the fixed effects model for the metaanalyses.When performing the analyses studies, different types of lowmolecularweight heparins were only entered into the same analysisif the dose of LMWH was judged to be comparable in anti-Xa units(20 mg enoxaparine equalize 2500 anti-Xa units) and presumingthe control groups were uniform.In studies evaluating the efficacy of mechanical prophylaxis,medical prophylaxis (or none) should be the same in both thetreated group and the control group within one study, but couldvary between studies.Heparins and mechanical methods for thromboprophylaxis in colorectal surgery (Review)Copyright © 2006 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd3

10.3, 2 studies, 111 patients) (observe inverse analysis)) with aPeto Odds ratio at 4.17 (95% Confidence Interval 1.37-12.70).The data on PE alone as outcome parameter were too sparse todraw any conclusions.D I S C U S S I O NDuring the performance of this review, the primary protocol wasviolated several times due to unexpected distribution of and limitedaccess to data. The violations were:- doppler-ultrasound was permitted as screening parameter, as itwas considered that the limited sensitivity of this type of investigationin asymptomatic patients (Mantoni 1997, Dauzat 1997)was equally distributed among the randomised groups.- neiher analysis of total mortality and/or fatal PE nor intentionto treat analyses were performed due to lack of data.- some non-blinded studies were included.No analyses of bleeding complications due to heterogeneity betweenthe method of computing and the fact, that the data wereunaccessible for colorectal patients in most studies, thus loosingthe ability to balance between efficacy and safety.These violations of the protocol might invalidate this review. Somestudies not fulfilling the original selection criteria were included,as the overall scientific methodology were judged to be reasonablefree of bias, and the results were considered to important to leaveout. If we have followed the original crieteria for selection only 10studies had been included, but the overall results and conclusionswould not have been altered.When evaluating the efficacy of thromboprophylaxis it has beena methodological demand to screen all patients with an objectivemethod as most postoperative TE are asymptomatic. One couldargue, that this is evaluating a treatment with a surrogate parameters,as the individual patient do not care, whether he/she experiencean asymptomatic TE. The most relevant endpoint wouldbe symptomatic DVT and/or PE, perhaps even fatal PE and/ortotal mortality. This would demand very large trials (up to 50,000in each treatment arm), but feasible in a multi centre setup. Thelargest thromboprophylactic trial ever performed is to our knowledgeGerman and showed that the incidence of fatal PE and totalmortality was the same after prophylaxis with either unfractionatedheparin or LMWH (Haas 1999). There is although a proportionalitybetween the incidence of fatal PE and asymptomaticTE (Wille-Jørgensen 1991), and it is shown that venous functionoften is impaired after even asymptomatic DVT, giving riseto chronic venous insufficiency (Siragusa 1997, Andersen 1991).Although not optimal, studies using sensitive screening methodscan in our opinion be used in evaluating the efficacy of variousprophylactic methods.There was no significant statistical heterogeneity among the studies,but the meta-analysis performed on all heparins versus notreatment or placebo (comparison 07) should be taken with somereserve, due to methodological heterogeneity between the studies.Also one should account for the different drugs and controlgroups being used in this analysis. As 10 out of 11 studies point inthe same direction the conclusion that heparin works is althoughconsidered valid.The analyses are invalidated by the many missing data, as we wereunable to retrieve data of colorectal patients from the primary authorsbut the results obtained are in agreement with other reviewsdealing with general surgery as a whole (Wille-Jørgensen 1991)except for one point. We were not able to find any differencebetween LMWH and LDH. Nurmohammed (Nurmohammed1992) found LMWH to be more effective in orthopaedic surgerybut not convincingly in general surgery a comprehensive metaanalysis.This analysis is although to be taken with care due tosevere heterogeneity. In a systematic review where meta-analysiswas omitted due to the heterogeneity (Jørgensen 1993), it wasconcluded that the two treatments do not differ substantially. Theefforts in retrieving the inaccessible data will continue and thisreview will be updated whenever new data on colorectal patientsare at hand.In the investigations with the combination regimens (Wille-Jørgensen 1986, Wille-Jorgensen 1991) unfractionated heparinwas used. There are no investigations in general surgery wherethe combination of LMWH and stockings has been investigated,but there is no reason to believe that different results would beobtained, if the unfractionated heparin was replaced by LMWHin the combination regimens. The combination regimen seems tobe the best, but there are limited data available and the data allcome the same author. An investigation in general surgery usinga paired design with stockings on one leg only (randomised toleft or right), thus comparing legs and not persons also showeda significant better effect of the combination as compared withunfractionated heparin alone (Törngren 1980). Due to the designthis study was not included in the analysis, but the result supportsour conclusion. Two of the studies awaiting assessment investigatesthe combination therapy (Borow 1983, Moser 1976). Thefirst find a significant better effect of the combination as comparedto heparin alone and the latter could not show any significancein a small sample size. Although these missing data comprise apublication bias, this is not considered to alter the conclusion.There are other ways to prevent postoperative DVT and/or PEthan heparins and stockings. Aspirin has during the last couple ofyears been shown to be somewhat effective (Collaborative 1994),but seemingly not as effective as heparins. No valid comparisonshave to our knowledge been made between aspirin and heparins.Heparins and mechanical methods for thromboprophylaxis in colorectal surgery (Review)Copyright © 2006 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd5

A U T H O R S ’Implications for practiceC O N C L U S I O N SBoth unfractionated heparin and low molecular weight heparincan be used as effective prophylaxis against postoperative thromboemboliccomplications after colorectal surgery. The optimalprophylaxis in colorectal surgery seems to be the combination ofgraded compression stockings and low-dose unfractionated heparin.The unfractionated heparin can likely be replaced with lowmolecular weight heparin.Implications for researchFurther effort to retrieve colorectal results from the many studieson general surgery should be continued. Large randomised trialsevaluating the use of the combination regime versus monotherapywith fatal pulmonary embolism as outcome should be performed.P O T E N T I A L C O N F L I C T O FI N T E R E S TOne of the reviewers (Morten Schnack Rasmussen) was part timeduring the review process working as a research fellow on longtermthrombosis prophylaxis. His salary was partly paid for by Pharmacia/Upjohn- a company which produces one of the compounds,which potentially occur in this review. The current review has noconnection to his work as a research fellow, despite being in thesame scientific area. The company had no influence on the review.No conflict of interest is considered to exist in this respect.The three other reviewers have no economical connection to thepharmaceutical industry with respect to this review, thus no conflictof interest exists.The primary reviewer has two papers included in the analyses.A C K N O W L E D G E M E N T SThe few primary authors (Maressi 1993, Onarheim 1986) whosupplied us with original data are greatly acknowledged.S O U R C E S O F S U P P O R TExternal sources of support• No sources of support suppliedInternal sources of support• H:S Central Research Fund DENMARKR E F E R E N C E SReferences to studies included in this reviewButson 1981 {published data only}Butson AR. Intermittent pneumatic calf compression for preventionof deep venous thrombosis in general abdominal surgery. Am J Surg1981;142(2):525–7. 82021671.Covey 1975 {published data only}∗ Covey TH, Sherman L, Baue AE. Low-dose heparin in postoperativepatients: a prospective, coded study. Arch Surg 1975;110:1021–1026.Fricker 1988 {published data only}∗ Fricker JP, Vergnes Y, Schach R, Heitz A, Eber M, Grunebaum L,et al. Low dose heparin versus low molecular weight heparin (Kabi2165, Fragmin) in the prophylaxis of thromboembolic complicationsof abdominal oncological surgery. Eur J Clin Invest 1988;18(6):561–567. 89137198.Gallus 1976 {published data only}∗ Gallus AS, Hirsh J, O’Brien SE, McBride JA, Tuttle RJ, Gent M.Prevention of venous thrombosis with small, subcutaneous doses ofheparin. JAMA 1976;235:1980–1982.Ho 1999 {published data only}Ho YH, Seow-Choen F, Leong A, Eu KW, Nyam D, Teoh MK.Randomized, controlled trial of low molecular weight heparin vs. nodeep vein thrombosis prophylaxis for major colon and rectal surgeryin Asian patients. Dis Colon Rectum 1999;42:196–203.Joffe 1976 {published data only}∗ Joffe S. Drug prevention of postoperative deep vein thrombosis.A compararative study of calcium heparinate and sodium pentosanpolysulfate. Arch Surg 1976;111:37–40.Koppenhagen 1992 {published data only}Koppenhagen K, Adolf J, Matthes M, Troster E, Roder JD, Hass S,et al. Low molecular weight heparin and prevention of postoperativethrombosis in abdominal surgery. Thromb Haemost 1992;67(6):627–30. 92376750.Kosir 1996 {published data only}∗ Kosir MA, Kozol RA, Perales A, McGee K, Beleski K, Lange P, etal. Is DVT prophylaxis overemphasized? A randomized prospectivestudy. J-Surg-Res 1996;60:289–92. CN-00006333 - CCTR. MED-LINE 96173505 EMBASE 96068622.Lahnborg 1974 {published data only}∗ Lahnborg G, Bergstrom K, Friman L, Lagergren H. Effect of lowdoseheparin on incidence of postoperative pulmonary embolismdetected by photoscanning. Lancet 1974;1:329–331.Maressi 1993 {published and unpublished data}∗ Maressi A, Balzano G, Mari G, D´ Angelo SV, Valle PD, Di Carlo V,et al. Prevention of Postoperative Deep Vein Thrombosis in CancerPatients. A Randomized Trial with Low Molecular Weight Heparin(CY 216). Int Surg 1993;78:166–70.Heparins and mechanical methods for thromboprophylaxis in colorectal surgery (Review)Copyright © 2006 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd6

Mcleod 2001 {published data only}∗ Mcleod RS, Geerts WH, Sniderman K, Greenwood C, GregoireRC Taylor BM, Silverman RE, Atkinson KG, Burnstein M, MarshallJC, Burul, CJ, Anderson DR, Ross T, Wilson SR, Barton P andother invetigators of the Canadian Colorectal Surgery DVT ProphylaxisTrial. Subcutaneous Heparin Versus Low-Molecular- WeightHeparin as Thromboprophylaxis in patients undergoung ColorectalSurgery. Results of the Canadian Colorectal DVT Prophylaxis Trial:A Randomized, Double-BlindTrial. Annals of Surgery 2001;233(3):438–444.Negus 1980 {published data only}∗ Negus D, Friedgood A. Ultra-low dose intravenous heparin in theprevention of postoperative deep vein thrombosis. Lancet 1980;1:891–894.Nicolaides 1983 {published data only}Nicolaides AN, Miles C, Hoare M, Jury P, Helmis E, Venniker R. Intermittentsequential pneumatic compression of the legs and thromboembolism-deterrentstockings in the prevention of postoperativedeep venous thrombosis. Surgery 1983;94(1):21–5. 83224179.Onarheim 1986 {published and unpublished data}Onarheim H, Lund T, Heimdal A, Arnesjo B. A low molecular weightheparin (KABI 2165) for prophylaxis of postoperative deep venousthrombosis. Acta Chir Scand 1986;152:593–596. 87123126.Rem 1975 {published data only}Rem J, Duckert F, Fridrich R, Gruber UF. Subcutaneous small heparindoses for the prevention of thrombosis in general surgery andurology [Subcutane kleine heparindosen zur thromboseprophylaxein der allgemeinen chirurgie und urologie]. Schweiz Med Wochenschr1975;105(26):827–35. 76129481.Torngren 1978 {published data only}∗ Torngren S, Forsberg K. Concentrated or diluted heparin prophylaxisof postoperative deep venous thrombosis. Acta-Chir-Scand 1978;144:283–285. CN-00202745 - CCTR. MEDLINE79100149 EMBASE 79071859.Valle 1988 {published data only}∗ Valle I, Sola G, Origone A. Controlled clinical study of the efficacyof a new low molecular weight heparin administered subcutaneouslyto prevent post-operative deep venous thrombosis. Curr-Med-Res-Opin 1988;11:80–86. CN-00068595 - CCTR. MEDLINE89120181.Wille-Jørgensen 1986 {published and unpublished data}∗ Wille-Jorgensen P. Lavdosis-heparin kombineret med enten dihyroergotamineller graderede støttestrømper [Low-dosage heparincombined with either dihydroergotamine or graduated supportivestockings. Combined prevention of thrombosis in colonic surgery]].Ugeskr Laeger 1986;148:501–503. 86181188.Wille-Jørgensen 1991 {published data only}∗ Wille-Jorgensen P, Hauch O, Dimo B, Christensen SW, JensenR, Hansen B. Prophylaxis of deep venous thrombosis after acuteabdominal operation. Surg Gynecol Obstet 1991;172:44–48.References to studies excluded from this reviewBounameaux 1993Bounameaux H, Huber O, Khabiri E, Schneider PA, Didier D,Rohner A. Unexpectedly high rate of phlebographic deep venousthrombosis following elective general abdominal surgery among patientsgiven prophylaxis with low-molecular-weight heparin. ArchSurg 1993;128:326–8.Browse 1974∗ Browse NL, Jackson BT, Mayo ME, Negus. The value of mechanicalmethods of preventing postoperative calf vein thrombosis. Br.J.Surg1974;61(3):219–23.Comerota 1986 AComerota AJ. Review of the Multicenter Trial Committee report: aprospective, randomized study on the prophylaxis of postoperativedeep venous thrombosis. Pharmacotherapy 1986;6:18S–22S.Ellis 1982Ellis H, Scurr JH. Prophylaxis of venous thrombosis. Phlebologie1982;35:135–42.Gallus 1993Gallus A, Cade J, Ockelford P, Hepburn S, Maas M, Magnani H,Bucknall T, Stevens J, Porteous F. Orgaran (Org 10172) or heparinfor preventing venous thrombosis after elective surgery for malignantdisease? A double-blind, randomised, multicentre comparison. ANZ-Organon Investigators’ Group. Thromb Haemost 1993;70:562–7.Kakkar 1993Kakkar VV. Multicentre randomized double-blind trial of low molecularweight heparin and standard heparin for prevention of postoperativevenous thromboembolism in major abdominal surgery. BritishJournal Of Surgery 1993;80:S112. CN-00128856.Mcleod 1995Mcleod RS, Geerts WH, Sniderman K, Greenwood C, Gregoire R,Taylor B, et al. Thromboprophylaxis in colorectal surgery - A randomizedtrial comparing low dose heparin and enoxaparin. Thrombosisand Haemostasis 1995;73(6):973, no 309.No author 1984No authors listed. Prophylactic efficacy of low-dose dihydroergotamineand heparin in postoperative deep venous thrombosis followingintra-abdominal operations. J Vasc Surg 1984;1:608–16.85058460.Rasmussen 1988Rasmussen A, Hansen PT, Lindholt J, Poulsen, T, Toftdahl DB,Gram J, Toftgaard C, Jespersen J. Venous thrombosis after abdominalsurgery. A comparison between subcutaneous heparin and antithromboticstockings, or both. J-Med 1988;19(3 and 4):193–201.CN-00068984 - CCTR. MEDLINE 89035909.Strand 1975Strand L, Bank-Mikkelsen OK, Lindewald H. Small heparin dosesas prophylaxis against deep-vein thrombosis in major surgery. Acta-Chir-Scand 1975;141:624–627. CN-00195984 - CCTR. MED-LINE 76108173.Torngren 1982Torngren S, Rieger A. Prophylaxis of deep venous thrombosis incolorectal surgery. Dis Colon Rectum 1982;25(6):563–6.Törngren 1980Torngren S. Low dose heparin and compression stockings in theprevention of postoperative deep venous thrombosis. Br J Surg 1980;67(7):482–4. 81022208.Heparins and mechanical methods for thromboprophylaxis in colorectal surgery (Review)Copyright © 2006 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd7

References to studies awaiting assessmentAdolf 1989Adolf J, Knee H, Roder JD, van de Flierdt E, Siewert JR. Thromboembolismprophylaxis with low molecular weight heparin in abdominalsurgery. Dtsch Med Wochenschr 1989;114:48–53.Bergqvist 1980Bergqvist D, Efsing HO, Hallbook T, Lindblad B. Prevention ofpostoperative thromboembolic complications. A prospective comparisonbetween dextran 70, dihydroergotamin, heparin and a sulphatedpolysaccharid. 146. Acta Chir Scand 1980;556:559–68.Bergqvist 1990 ABergqvist D, Burmark US, Frisell J, Guilbaud O, Hallbook T, HornA, et al. Thromboprophylactic effect of low molecular weight heparinstarted in the evening before elective general abdominal surgery: acomparison with low-dose heparin. Semin Thromb Hemost 1990;16Suppl:19–24.Bergqvist 1986 ABergqvist D. Low molecular weight heparin once daily comparedwith conventional low-dose heparin twice daily. A prosepctive double-blindmulticentre trial on prevention of postoperative thrombosis.Br.J.Surg 1986;73:204–8.Bergqvist 1986 BBergqvist D, Burmark US, Frisell J, Hallbook T, Lindblad B, RisbergB, et al. Prospective double-blind comparison between Fragminand conventional low-dose heparin: thromboprophylactic effect andbleeding complications. Haemostasis 1986;16 Suppl:2:11–8.Bergqvist 1988 BBergqvist D, Matzsch T, Burmark US, Frisell J, Guilbaud O, HallbookT, et al. Low molecular weight heparin given the evening beforesurgery compared with conventional low-dose heparin in preventionof thrombosis [published erratum appears in Br J Surg 1988 Nov;75(11):1077]. Br J Surg 1988;75(11):888–91.Bergqvist 1990 BBergqvist D, Burmark US, Frisell J, Guilbaud O, Hallbook T, HornA, et al. Thromboprophylactic effect of low molecular weight heparinstarted in the evening before elective general abdominal surgery: acomparison with low-dose heparin. Semin Thromb Hemost 1990;16Suppl.:19–24.Bergqvist 1992Bergqvist D, Lindgren B, Matzsch T. Glycosaminnoglycans in prophylaxisagainst venous thromboembolism. Adv Exp Med Biol 1992;313:259–74.Bergqvist 1995Bergqvist D, Burmark US, Flordal PA, Frisell J, Hallbook T, HedbergM, et al. Low molecular weight heparin started before surgery asprophylaxis against deep vein thrombosis: 2500 versus 5000 XaI unitsin 2070 patients. British Journal of Surgery 1995;82:496–501.Bergqvist 1996Bergqvist D, Flordal PA, Friberg B, Frisell J, Hedberg M, LjungstromKG, et al. Thromboprophylaxis with a low molecular weight heparin(tinzaparin) in emergency abdominal surgery. A double-blind multicentertrial. Vasa 1996;25:156–60.Boneu 1993Boneu B. An international multicentre study: Clivarin in the preventionof venous thromboembolism in patients undergoing generalsurgery. Report of the International Clivarin Assessment Group..Blood Coagul Fibrinolysis 1993;4 Suppl 1:S21–2.Borow 1983Borow M, Goldson HJ. Prevention of Postoperative Deep VenousThrombosis and Pulmonary Emboli with Combined Modalities. AmSurg 1983;49:599–605.Breddin 1983Breddin K, Haring R, Koppenhagen K. Prevention of postoperativethrombotic complications with heparin and dihydroergotamine. Arandomized double-blind study. Dtsch Med Wochenschr 1983;108:98–102.Buttermann 1977Buttermann G, Theisinger W, Weidenbach A, Hartung R, WelzelD, Pabst HW. [Quantitative assessment of drug-induced prophylaxisof postoperative thromboembolism. Comparison of frequencies ofdeep vein thrombosis and pulmonary embolism using acetylsalicylicacid,dextran, dihydroergotamine, low-dose heparin and the fixedcombination of heparin and dihydroergotamine (author’s transl)].Med Klin 1977;72:1624–38.Cade 1987Cade JF, Wood M, Magnani HN, Westlake GW. Early clinical experienceof a new heparinoid, Org 10172, in prevention of deep venousthrombosis. Thromb Res 1987;45:497–503.Caen 1988Caen JP. A randomized double-blind study between a low molecularweight heparin Kabi 2165 and standard heparin in the prevention ofdeep vein thrombosis in general surgery. A French multicenter trial.Thromb Haemost 1988;59:216–20.Comerota 1986 BComerota AJ, White JV. The use of dihydroergotamine and heparinin the prophylaxis of deep venous thrombosis. Chest 1986;89:389S–95S.Creperio 1990Creperio G, Marabini M, Ciocia G, Bergonzi M, Fincato M. [Evaluationof the effectiveness and safety of Fragmin (Kabi 2165) versuscalcium heparin in the prevention of deep venous thrombosis ingeneral surgery]. Minerva Chir 1990;45:1101–6.EFS 1988The European Fraxiparin Study (EFS) Group. Comparison of a lowmolecular weight heparin and unfractionated heparin for the preventionof deep vein thrombosis in patients undergoing abdominalsurgery. The European Fraxiparin Study (EFS) Group. Br J Surg1988;75:1058–63.Encke 1988Encke A. Comparison of a low molecular weight heparin and unfractionatedheparin for the prevention of deep vein thrombosis inpatients undergoing abdominal surgery. Br J Surg 1988;75:1058–63.Enoxacan 1997Enoxacan Study Group. Efficacy and safety of enoxaparin versus unfractionatedheparin for prevention of deep vein thrombosis in electivecancer surgery: a double-blind randomized multicentre trial withvenographic assessment. ENOXACAN Study Group. Br J Surg 1997;84:1099–103.Garcea 1992Garcea D, Martuzzi F, Santelmo N, Savoia M, Casertano MG, FurnoA, et al. Post-surgical deep vein thrombosis prevention: evaluationHeparins and mechanical methods for thromboprophylaxis in colorectal surgery (Review)Copyright © 2006 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd8

of the risk/benefit ratio of fractionated and unfractionated heparin.Curr Med Res Opin 1992;12:572–83.Gazzaniga 1993Gazzaniga GM, Angelini G, Pastorino G, Santoro E, Lucchini M,Dal Pra ML. Enoxaparin in the prevention of deep venous thrombosisafter major surgery: multicentric study. The Italian Study Group. IntSurg 1993;78:271–5.Gruber 1977Gruber UF, Duckert F, Fridrich R, Torhorst J, Rem J. Prevention ofpostoperative thromboembolism by dextran 40, low doses of heparin,or xantinol nicotinate. Lancet 1977;1:207–10.Hartl 1990Hartl P, Brucke P, Dienstl E, Vinazzer H. Prophylaxis of thromboembolismin general surgery: comparison between standard heparin andFragming. Thromb Res 1990;57:577–84.Heather 1982Heather BP, Greenhalgh RM. Prophylaxis of early post operative deepvenous thrombosis by monitored heparin infusion. Phlebologie 1982;35:173–85.Kakkar 1972Kakkar VV, Corrigan T, Spindler J, Fossard DP, Flute PT, Crellin RQ.Efficacy of low doses of heparin in prevention of deepvein thrombosisafter major surgery. Lancet 1972;2:101–5.Kakkar 1985Kakkar VV, Murray WJ. Efficacy and safety of low-molecular-weightheparin (CY216) in preventing postoperative venous thrombo-embolism:a co-operative study. Br J Surg 1985;72:786–91.Kakkar 1986Kakkar VV, Kakkar S, Sanderson RM, Peers CE. Efficacy and safetyof two regimens of low molecular weight heparin fragment (Fragmin)in preventing postoperative venous thrombolism. Haemostasis 1986;16 Suppl 2:19–24.Kakkar 1993Kakkar VV, Cohen AT, Edmonson RA, Phillips MJ, Cooper DJ, DasS, et al. Low molecular weight versus standard heparin for preventionof venous thromboembolism after major abdominal surgery. TheThromboprophylaxis Collaborative Group [see comments]. Lancet1993;341:259–65.Kakkar 1997Kakkar VV, Boeckl O, Boneu B, Bordenave L, Brehm OA, Brucke P,et al. Efficacy and safety of a low-molecular-weight heparin and standardunfractionated heparin for prophylaxis of postoperative venousthromboembolism: European multicenter trial. World J Surg 1997;21:2-8; discussion 8-9.Koller 1986Koller M, Schoch U, Buchmann P, Largiader F, von Felten A, FrickPG. Thrombosis prophylaxis in visceral surgery with the low molecularweight heparin fragment Kabi 2165 (7,500 and 2,500 anti-XaIU/day). Haemostasis 1986;16 Suppl 2:69–70.Kosir 1998Kosir MA, Schmittinger L, Barno Winarski L, Duddella P, PoneM, Perales A, et al. Prospective double-arm study of fibrinolysis insurgical patients. J Surg Res 1998;74:96–101.Lahnborg 1975Lahnborg G, Bergstrom K. Clinical and haemostatic parameters relatedto thromboembolism and low-dose heparin prophylaxis in majorsurgery. Acta Chir Scand 1975;141(7):590–5.Lareng 1978Lareng L, Vaysse C, Plante J, Boneu B, Gouzi M. Prevention of postoperativethromboembolic disease in general surgery. A randomizedtrial of two therapeutic procedures evaluated by the method of I labelledfibrinogen. Anaesth Analg (Paris) 1978;35(6):1185–93.Leypold 1984Leypold J, Privara M, Stepankova S. [Prevention of postoperativethromboembolic accidents using small doses of heparin]. Rozhl Chir1984;63(8-9):611–5.Liezorovicz 1991Liezorovicz A, Picolet H, Peyrieux JC, Boissel JP. Prevention of perioperativedeep vein thrombosis in general surgery: a multicentredouble blind study comparing two doses of Logiparin and standardheparin. H.B.P.M. Research Group. Br J Surg 1991;78:412–16.Limmer 1994Limmer J, Ellbruck D, Muller H, et al. Prospective randomized clinicalstudy in general surgery comparing a new low molecular weightheparin with unfractionated heparin in the prevention of thrombosis.Clin Investig 1994;72:913–9.Marassi 1993Marassi A, Balzano G, Mari G, et al. Prevention of postoperativedeep vein thrombosis in cancer patients. A randomized trial with lowmolecular weight heparin (CY 216). Int Surg 1993;78:166–70.McLeod 1996McLeod RS. The risk of thromboembolism in patients undergoingcolorectal surgery. Drugs 1996;52 Suppl 7:38–41.Moreno 1996Moreno Gonzalez E, Fontcuberta J, de la Llama F. Prophylaxis ofthromboembolic disease with RO-11 (ROVI), during abdominalsurgery. EMRO1 (Grupo Fstudio Multicintrico RO-11). Hepatogastroenterology1996;43:744–7.Moser 1976Moser G, Froideveaux A. Prophylaxis of Post-operative deep venousthrombosis using small sub-cutaneous heparin doses, associated ornot with compressive stockings: comparative study and results [Prophylaxxiedes thromboses veineuses profondes postopératoires pardes petites doses d´ Heparin souscutanes associées ou non au port debas compressif: étude comparative et résultats]. Schweiz RundschauMed 1976;65:1015–20..Mühe 1984Mühe E. Intermittent sequential high-pressure compression of theleg. A new method of preventing deep vein thrombosis. Am J Surg1984;147(6):781–5.Negus 1982Negus D, Friedgood A. Ultra-low dose intravenous heparin in theprevention of postoperative deep vein thrombosis. Phlebologie 1982;35:247–58.Nicolaides 1972Nicolaides AN, Dupont P, Douglas N, Lewis JD, Desai S, JamiesonCW. Small doses of subcutaneous hepatin preventing deep.veinthrombosis in major surgery. Br.J.Surg 1972;59:911.Heparins and mechanical methods for thromboprophylaxis in colorectal surgery (Review)Copyright © 2006 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd9

Nurmohamed 1995Nurmohamed MT, Verhaeghe R, Haas S, Iriarte JA, Vogel G, vanRij AM, et al. A comparative trial of a low molecular weight heparin(enoxaparin) versus standard heparin for the prophylaxis of postoperativedeep vein thrombosis in general surgery. Am J Surg 1995;169:567–71.Ockelford 1989Ockelford PA, Patterson J, Johns AS. A double-blind randomizedplacebo controlled trial of thromboprophylaxis in major elective generalsurgery using once daily injections of a low molecular weightheparin fragment (Fragmin). Thromb Haemost 1989;62:1046–9.Pezzuoli 1989Pezzuoli G, Neri Serneri GG, Settembrini P, Coggi G, Olivari N,Buzzetti G, et al. Prophylaxis of fatal pulmonary embolism in generalsurgery using low-molecular weight heparin Cy 216: a multicentre,double-blind, randomized, controlled, clinical trial versus placebo(STEP). STEP-Study Group. Int Surg 1989;74:205–10.Pezzuoli 1990Codemo R, Galli G, Roveri S. Pezzuoli G, Neri-Serneri GG, SettembriniPG, Coggi G, OlivariN, Negri G, Codemo R, Galli G, Roveri S.Effectiveness and safety of the low-molecular-weight heparin CY 216in the prevention of fatal pulmonary embolism and thromboembolicdeath in general surgery. A multicentre, double-blind, randomized,controlled clinical trial versus placebo (STEP). STEP Study Group.Haemostatis 1990;20 Suppl. 1:193–204.Plante 1979Plante J, Boneu B, Vaysse C, Barret A, Gouzi M, Bierme R. Dipyridamole-aspirinversus low doses of heparin in the prophylaxis of deepvenous thrombosis in abdominal surgery. Thromb Res. 14 1979;14:399–403.Roberts 1974Roberts VC CL. Prevention of postoperative deep vein thrombosisin patients with malignant disease. British Medical Journal 1974;1:358–60.Rodiger 1991Rodiger H, Nowak W, Kneist W. [Quality requirements in clinicalstudies in surgery exemplified by prevention of thromboembolism].Zentralbl Chir 1991;116:757–60.Rosenberg 1975Rosenberg IL EMPA. Prophylaxis of postoperative leg vein thrombosisby low dose subcutaneous heparin or perioperative calf musclestimulation: A controlled clinical trial. BMJ 1975;1:649–51.Samama 1988Samama M, Bernard P, Bonnardot JP, Combe-Tamzali S, Lanson Y,Tissot E. Low molecular weight heparin compared with unfractionatedheparin in prevention of postoperative thrombosis. Br J Surg1988;75:128–31.Samama 1989Samama M, Combe-Tamzali S. Prevention of thromboembolic diseasein general surgery with enoxaparin. Br.J.Clin.Pract.suppl 1989;65:9–17.Samama 1990Samama M, Combe S. Prevention of thromboembolic disease ingeneral surgery with enoxaparin (Clexane). Acta Chir Scand Suppl1990;556:91–5.Samama 1994Samama MM. Prevention of postoperative thromboembolism in generalsurgery with enoxaparin. Ann Cardiol Angeiol (Paris) 1994;43:31–3.Schmitz 1984Schmitz Huebner U, Bunte H, Freise G, Reers B, Ruschemeyer C,Scherer R, et al. Clinical efficacy of low molecular weight heparinin postoperative thrombosis prophylaxis. Klin Wochenschr 1984;62:349–53.Torngren 1984Torngren S, Kettunen K, Lahtinen J, Koppenhagen K, Brucke P,Hartl P, et al. A randomized study of a semisynthetic heparin analogueand heparin in prophylaxis of deep vein thrombosis. Br J Surg 1984;71:817–20.Verardi 1988Verardi S, Casciani CU, Nicora E, et al. A multicentre study onLMW-heparin effectiveness in preventing postsurgical thrombosis.Int Angiol 1988;7:19–24.Zawilska 1990Meissner J, Karon J, Lewandowski K, Lopaciuk S, et al. ZawilskaK, Tokarz A, Misiak A, Psuja P, Wislawski S, Szymczak P, MeissnerJ, Karon J, Lewandowski K, Lopaciuk S, et al. Nebulized heparinand anabolic steroid in the prevention of postoperative deep veinthrombosis following elective abdominal surgery. Folia Haematol IntMag Klin Morphol Blutforsch 1990;117:699–707.Additional referencesAmarigiri 2000Amagiri SV, Lees TA. Elastic compression stockings for the preventionof deep vein theombosis (Cochrane Review). In: In. The CochraneLibrary, 3, 2000. Oxford: Update Software.Andersen 1991Andersen M, Wille-Jørgensen P. Late complications of asymptomaticdeep venous thrombosis. Eur J Surg 1991, 157:527-530. AndersenM, Wille-Jørgensen P. Late complications of asymptomatic deep venousthrombosis Late complications of asymptomatic deep venousthrombosis. Eur J Surg Eur J Surg 1991;157:527-530 1991;157 157:527-530.:527–30.Clagett 1995Clagett GP, Anderson FA, Heit J, Levine MN, Wheeler HB. Preventionof venous thromboembolism. Chest 1995. Chest 1995;108:312s–33s.Clagett 1988Clagett GP, Reisch JS. Prevention of venous thromboembolism ingeneral surgical patients. Ann Surg 1988;208:227–40. 88293064.Collaborative 1994Collaborative overview. Collaborative overview of randomised trialsof antoplatelet therapy - III: reduction in venous thrombosis andpulmonary embolism by antiplatelet prophylaxis among surgical andmedical patients. BMJ 1994;308:235–46.Collins et al 1988Collins R, Scrimgeour A, Yusuf S, Peto R. Reduction of fatal pulmonaryembolism and venous thrombosis by perioperative administrationof subcutaneous heparin. N Engl J Med 1988;318:1162–73.CN-00072000 - CCTR. MEDLINE 88202030.Heparins and mechanical methods for thromboprophylaxis in colorectal surgery (Review)Copyright © 2006 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd10

Dauzat 1997Dauzat M, Laroche JP, Deklunder G, Ayoub, J, Quére I, Lopez FM,Janbon C. Diagnosis of acute lower limb deep venous thrombosiswith ultrasound: trends ans controversies. J Clin Ultrasound 1997;25(7):343–58. 97426095.Haas 1999Haas SK, Wolf H, Encke A, Fareed J. Prevention of fatal pulmonaryembolism by low molecular weight heparin - a double blind comparisonof certoparin and unfractionated heparin. Thromb HaemostasAugust 1999;Supplement:491.Jørgensen 1993Jorgensen LN, Wille-Jorgensen P, Hauch O. Prophylaxis of postoperativethrom boembolism with low molecular weight heparins. Br JSurg 1993;80:689–704. 93321028.Kjaergaard 1985Kjaergaard J, Esbensen K, Wille Jorgensen P, Jorgensen T, Thorup J,Berning H, Wold S. A multivariate pattern recognition study of riskfactorsindicating postoperative thromboembolism despite low-doseheparin in major abdominal surgery. Thromb Haemost 1985;54(2):409–12. 86097628.Leizorovicz 1997Leizorovicz A, Haugh MC. Low Molecular weight heparinin preventionof perioperative thrombosis (Protocol). In: Fowkes FGR, JanzonL, Kleijnen J, leng CG (eds.) Pripheral Vascular Diseases Moduleon The Cochrane Database of Systematic Reviews, (updated August1997). Available in The Cochrane Library (database on CDROM).The Cochrane Collaboration; Issue 4. Oxford: Update Software;1997. In: Cochrane Library, 3, 2000. Oxford: Update Software.Leizorovicz 1992Leizorovicz A, Haugh MC, Chapuis FR, Samama MM, BoisselJP. Low molecular weight hepaprin in prevention of perioperativethrombosis. Brit Med J 1992;305:913–20. 93091577.Mantoni 1997Mantoni M, Strandberg C, Neergaard K, Sloth C, Jørgensen PS,Thamsen H, Tørholm C, Paaske BP, Rasmussen SW, ChristensenSW, Wille-Jørgensen P. Triplex US in the diagnosis of asymptomaticdeep venous thrombosis. Acta Radiol 1997;38(2):327–31.97247030.Nurmohammed 1992Nurmohamed MT, Rosendaal FR, Buller HR, et al. Low molecularweight heparin versus standard heparin in general and orthopaedicsurgery: a meta-analysis. Lancet 1992;340:152–56. 92326472.Siragusa 1997Siragusa S, Beltrametti C, Barone M, Piovella F. Clinical course andincidence of post-thrombophlebitic syndrome after profound asymptomaticdeep vein thrombosis. Minerva Cardioangiol 1997;45:57–66.Wille-Jorgensen 1991Wille-Jørgensen, P. Prophylaxis of postoperative thromboembolism.Danish Medical Bulletin 1991;38:203–28.Wille-Jørgensen 1988Wille-Jørgensen P, Kjaergaard J, Jørgensen T, Korsgaard Larsen T.Failure in prophylactic management of thromboembolic disease incolorectal surgery. Dis Colon Rectum 1988;31:384–6. 1988211380.Wille-Jørgensen 1990Wille-Jorgensen P, Ott P. Predicting failure of low.dose prophylacticheparin in general surgical patients. Surg Gynecol Obstet 1990;171:126–30.Wille-Jørgensen 1992Wille-Jørgensen P, Jørgensen LN, Hauch O, Borris LC, Lassen MR,Nehen AM, Kjær L, Jensen R. Potential influence of observer variationon thromboprophylactic studies. Hæmostasis 1992;22:211–5.∗ Indicates the major publication for the studyT A B L E SCharacteristics of included studiesStudy Butson 1981MethodsParticipantsInterventionsOutcomesRCT. Sealed envelopes. Not blinded. (Controlgroup = no treatment). No primary stratification of colorectalpatients.Elective general surgery patients. 119 randomized. Non excluded. Leaving 119 patients in per protocolanalysis as well as in intention to treat analysis. Subgroup of 24 colorectal patients were distributed withrespectively 63 % and 37 % in the two treatment arms.Intermittent compression: Intermittent compression peroperatively and untill ambulant. Most of the patients24 to 48 hours postoperatively.Control: No treatment.Thromboembolic events: DVTBleeding events: Not described.Diagnosis: radiofibrinogen uptake test every day up to 14 days postoperatively or untill discharge. If positivetest then confirmed with venography.Heparins and mechanical methods for thromboprophylaxis in colorectal surgery (Review)Copyright © 2006 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd11

Characteristics of included studies (Continued )NotesAllocation concealmentBoth intention to treat- and per protocol analysis.Unbalanced distribution of colorectal patients.AStudy Covey 1975MethodsParticipantsInterventionsOutcomesNotesAllocation concealmentRCT. Coded vials. Patient-, surgeon- and outcome-assessor blinded. No primary stratification of colorectalpatients.Elective general surgery patients. 105 randomized. Non excluded. Leaving 105 patients in per protocolanalysis as well as in intention to treat analysis. Subgroup of 20 colorectal patients were distributed withrespectively 45% and 55% in the two treatment arms.LDH: 5000 U unfractionated heparin preoperatively and x2 postoperatively for 8 days or until discharge.Control group: PlaceboThromboembolic events: DVTBleeding events: Not described.Diagnosis: radiofibrinogen uptake test, until 8 th day.No missing patients.Balanced distribution of colorectal patients.BStudy Fricker 1988MethodsParticipantsInterventionsOutcomesNotesAllocation concealmentRCT. Unclear randomizing procedure. Not blinded. No primary stratification of colorectal patients.Elective cancer general surgery. 80 randomized patients. Non excluded. Leaving 80 patients in per protocolanalysis as well as in intention to treat analysis. Subgroup of 6 colorectal patients were distributed withrespectively 33% and 67% in the two treatment arms.LDH: 5000 IU unfractionated heparin preoperatively and x3 postoperatively for ten days.LMWH: 2500 anti-Xa units (lowdose) preoperatively and 5000 anti-Xa units (mediumdose) x1 for ten dayspostoperatively.Thromboembolic events: PEBleeding events: Not specified in colorectal patientsDiagnosis: Radiofibrinogen uptake test. Positiv test confirmed by phlebography. PE: Clinically, confirmedby scintigraphy.Both intention to treat- and per protocol analysis.Unbalanced distribution of colorectal patients.BStudy Gallus 1976MethodsParticipantsRCT. Sealed envelopes. Surgeon blinded. Not patient nor outcome-assessor blinded. (Controlgroup = notreatment).No primary stratification of colorectal patients.Elective general surgery patients. 820 randomized patients. Non excluded. Leaving 820 patients in perprotocol analysis as well as in intention to treat analysis. Subgroup of 90 colorectal patients were distributedwith respectively 49 % and 51 % in the two treatment arms.Interventions LDH: 5000 units of unfractionated heparin preoperatively and x3 postoperatively for seven days .Control: No treatmentOutcomesThromboembolic events: DVTBleeding events: Not specified in colorectal patients.Heparins and mechanical methods for thromboprophylaxis in colorectal surgery (Review)Copyright © 2006 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd12

Characteristics of included studies (Continued )Diagnosis: radiofibrinogen uptake test, 1 to 7 th day.NotesAllocation concealmentIntention to treat analysis.Balanced distribution of colorectal patients.AStudy Ho 1999MethodsRCT. Sealed envelopes. Surgeon blinded. Not patient nor outcome-assessor blinded. (Controlgroup = notreatment)Participants Elective surgical colorectal patients. 320 randomized patients. 17 excluded in LMWH group. Leaving 303patients in per protocol-analysis.InterventionsOutcomesLWMH: Enoxaparin 20 mg preoperativelyand 40 mgx1 postoperatively at least 4 days or until ambulant.Control: No treatment.Thromboembolic:DVT, PE, Fatal PE, overall mortality.Bleeding: Intraoperativly bloodlosses, drainage output, number of bloodtransfusions and postoperativelyrelated complications.Diagnosis: Clinical every day and doppler ultrasound on 3 th and 5 th post- operative dayNotesAllocation concealment17 patients missing. No intention to treat analysisAStudy Joffe 1976MethodsParticipantsInterventionsOutcomesNotesAllocation concealmentRCT. Computer generated list. Not blinded. No primary stratification of colorectal patients.Elective general surgery patients. 220 randomized patients. 17 excluded. Leaving 203 patients in per protocolanalysis. Subgroup of 17 colorectal patients were distributed with respectively 47%, 18 % and 35% inthe three treatment arms. Treatment arm with pentosan excluded from this analysis. Leaving 14 colorectalpatients in analysis.LDH:5000 units of unfractionated heparin preoperatively and x3 postoperatively for seven days.Pentosan: 50 mg preoperatively and x2 postoperatively for seven days.Control group: No treatment.Thromboembolic events: DVT.Bleeding events:Not specified in colorectal patients.Diagnosis: Radiofibrinogen uptake test17 patients missing. No intention to treat analysis.Unbalanced distribution of colorectal patients.BStudy Koppenhagen 1992MethodsParticipantsInterventionsOutcomesRCT. Unclear randomizing procedure. Patient, surgeon and outcome-assessor blinded.No primary stratification of colorectal patients.Elective surgical abdominal patients. 673 randomized patients. 20 excluded. Leaving 653 in per protocolanalysis.Subgroup of 195 colorectal patients distributed with respectively 53% and 47% in the two treatmentarms.LWMH: 3000 anti Xa units (medium dose) pre- operatively and 3000 anti Xa units plus two placeboinjections daily for a mean of 7.5 postoperative days.LDH: 5000 units of unfractionated heparin pre- operatively and x3 postoperatively for a mean of 7.4 days.Thromboembolic: DVT. PE, fatal PE and overall mortality not described in colorectal patients.Bleeding: not specified in colorectal patients.Heparins and mechanical methods for thromboprophylaxis in colorectal surgery (Review)Copyright © 2006 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd13

Characteristics of included studies (Continued )NotesAllocation concealmentDiagnosis: Either radiofibrinogen uptake test or phlebography. Daily.20 patients missing. No intention to treat analysis.Balanced distribution of colorectal patients.BStudy Kosir 1996MethodsParticipantsInterventionsOutcomesNotesAllocation concealmentRCT. Unclear randomizing procedure. Not blinded. No primary stratification of colorectal patients.Elective general surgery patients. Subgroup of 12 colorectal patients. 137 randomized patients. 29 excluded.Leaving 108 in per protocol analysis. Subgroup of Colorectal patients were distributed with respectively 17% , 25% and 58 % in the three treatment group.Intermittent compression: Intermittent compression peroperatively and for 48 hours postoperatively.LDH: 5000 units of unfractionated heparin preoperatively and x2 postoperatively for seven days.Control: No treatment.Thromboembolic events: DVTBleeding events: Not described.Diagnosis: Doppler ultrasound at 1 th, 3 th and 30 th day.29 missing patients. No intention to treat analysis. Unbalanced distribution of colorectal patients.BStudy Lahnborg 1974MethodsParticipantsInterventionsOutcomesNotesAllocation concealmentRCT. Coded vials. Patient-, surgeon- and outcome-assessor blinded. No primary stratification of colorectalpatients.Elective general surgery patients. 112 randomized patients. Non excluded. Leaving 112 patients in perprotocol analysis as well as in intention to treat analysis. Subgroup of 19 colorectal patients were distributedwith respectively 58 % and 42 % in the two treatment arms.LDH: 5000 U unfractionated heparin preoperatively and x2 postoperatively for five days.Control: Placebo injection.Thromboembolic events: DVT, PE and TE.Bleeding events: Not described.Diagnosis: Radiofibrinogen uptake test.No missing patients.Balanced distribution of colorectal patients.AStudy Maressi 1993MethodsRCT. Unclear randomization procedure. Open studyParticipantsElective gastrointestinal patientsInterventions LMWH: 3,825 I aXa Units preoperativelyControl: No treatmentOutcomesDVT defined as positive FUTNotesHalf of postive FUT were verified by venographyAllocation concealment BStudy Mcleod 2001MethodsRCT. Computer generated randomization. Patient-, surgeon- and outcome-assesor blinded. Multicentricstudie.Heparins and mechanical methods for thromboprophylaxis in colorectal surgery (Review)Copyright © 2006 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd14

Characteristics of included studies (Continued )ParticipantsInterventionsOutcomesNotesAllocation concealmentElective colorectal patients. 1349 patients randomized. 413 excluded. Leaving 936 patients in per protocolanalysis.LDH: 5000 U unfractionated heparin preoperatively and x2 postoperatively. Duration not stated.LMWH: 40 mg enoxaparin X 1 plus saline injection X 1. Duration was up to 10 days.Thromboembolic events: DVT or PEBleeding events: Major bleeding events.Diagnosis: Venography on 5 th to 9 th day.413 missing patients. No intention to treat analysis.AStudy Negus 1980MethodsParticipantsInterventionsOutcomesNotesAllocation concealmentRCT. Sealed envelopes. Patient-, surgeon- and outcome-assessor blinded. No primary stratification of colorectalpatients.Elective general surgery patients. 105 enrolled, 95 randomized patients. 10 patients excluded before randomizingprocedure. Leaving 95 patients in per protocol analysis. Subgroup of 33 colorectal patients weredistributed with respectively 42 % and 58 % in the two treatment arms.Heparin: Iv. heparin 1IU/kgxh peroperatively, the first 48 hours and uptil five days postoperatively.Control group: Iv. salineThromboembolic events: TE. Covering both DVT and PE.Bleeding events: Not specified in colorectal patients.Diagnosis: Radiofibrinogen uptake test, every second day until 6 th or 8 th postoperative day.10 patients missing. No intention to treat analysis.Balanced distribution of colorectal patients.AStudy Nicolaides 1983MethodsParticipantsInterventionsOutcomesNotesAllocation concealmentRCT. Sealed envelopes. Not blinded. No primary stratification of colorectal patients.Elective surgical abdominal patients. 150 randomized patients. Non excluded. Leaving 150 patients in perprotocolanalysis as well as in intention to treat analysis. Subgroup of 31 colorectal patients were distributedwith respectively 26%, 35% and 39 % in the three treatment arms.Electrical calf stimulation: Peroperatively.LDH: 5000 units of unfractionated heparin preoperatively and x2 postoperatively untill discharge.Intermittent compression/stockings: Intermittent compression peroperatively and at least for 72 hours postoperatively.When ambulant; TED- stockings.Thromboembolic events: DVT. PE, fatal PE and overall mortality not described.Bleeding: Not described.Diagnosis: Radiofibrinogen uptake test, dailyNo missing patients. 3 treatmentgroups.Balanced distribution of colorectal patients.AStudy Onarheim 1986MethodsRCT. Unclear randomizing procedure. Patient-, surgeon- and outcome-assessor blinded. No primary stratificationof colorectal patients.Heparins and mechanical methods for thromboprophylaxis in colorectal surgery (Review)Copyright © 2006 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd15

Characteristics of included studies (Continued )ParticipantsInterventionsOutcomesNotesAllocation concealmentElective surgical abdominal patients. 52 randomized patients. 1 patient excluded. Leaving 51 in per protocolanalysis. Subgroup of 46 colorectal patients were distributed with respectively 48% and 52% in the twotreatment arms.LMWH: 5000 anti-x-activated (medium dose) units preoperatively and x1 plus placebo x1 postoperativelyfor six days.LDH: 5000 U unfractionated heparin preoperatively and eigth o´ cloc p.m. at the day of surgery and x2postoperatively for six days.Thromboembolic events: DVTBleeding events: Not specified in colorectal patients.Diagnosis: Radiofibrinogen uptake test every day or every second day for at least 7 days.1 missing patient.Balanced distribution of colorectal patients.BStudy Rem 1975MethodsParticipantsInterventionsOutcomesNotesAllocation concealmentRCT. Sealed envelopes. Surgeon blinded. Not patient nor outcome-assessor blinded. (Control group = notreatment).No primary stratification of colorectal patients.Elective surgical abdominal- and urological patients. 212 randomized patients. 22 excluded patients in LDHarm and 12 excluded patients in no treatment arm. Leaving 178 patients in per protocol analysis. Subgroupof 31 colorectal patients were distributed with respectively 61% and 39% in the two treatment arms.LDH: 5000 units of unfractionated heparin preoperatively and x3 postoperatively for at least 7 days.Control: No treatment.Thromboembolic events: DVT.Bleeding: Not specified in colorectal patientsDiagnosis: Rradiofibrinogen uptake test, daily34 patients missing. No intention to treat analysis.Unbalanced distribution of colorectal patients.AStudy Torngren 1978MethodsParticipantsInterventionsOutcomesNotesAllocation concealmentRCT. Coded vials. Patient-, surgeon- and outcome-assessor blinded. No primary stratification of colorectalpatients.Elective surgical abdominal patients. 175 randomized patients. From the three arm were respectively excluded3, 4 and 1 patient. Leaving 167 patients in per protocol analysis. Subgroup of 107 colorectal patients weredistributed with respectively 38%, 30% and 32 % in the three arms.LDH: 5000 u unfrationated heparin preoperatively and x2 postoperatively for 6 to 8 days.HDH: 25000 u unfrationated heparin preoperatively and x2 postoperatively for 6 to 8 days.Control group: PlaceboThromboembolic events: DVTBleeding events: Not specified in colorectal patients.Diagnosis: Radiofrbinogen uptake test performed at a mean of 10.5 days.8 missing patients. No intention to treat analysis.Balanced distribution of colorectal patients.AHeparins and mechanical methods for thromboprophylaxis in colorectal surgery (Review)Copyright © 2006 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd16

Characteristics of included studies (Continued )Study Valle 1988MethodsParticipantsInterventionsOutcomesNotesAllocation concealmentRCT. Unclear randomizing procedure. Patient-, surgeon- and outcome-assessor blinded. No primary stratificationof colorectal patients.Elective general surgery patients. 100 randomized patients. Non excluded. Leaving 100 patiens in per protocolanalysis as well as in intention to treat analysis. Subgroup of 11 colorectal patients were distributed withrespectively 55 % and 45 % in the two arms.LMWH: 7500 anti-x-activated (highdose) preoperatively and x1 postoperatively for seven days.Control group: PlaceboThromboembolic events:DVTBleeding events: Not specified in colorectal patients.Diagnosis: Clinically and doppler sonography.Balanced distribution of colorectal patients.BStudy Wille-Jørgensen 1986MethodsParticipantsInterventionsOutcomesNotesAllocation concealmentRCT. Computergenerated list. Not blinded.Elective colorectal patients. 86 patients randomized. 5 excluded in LDH - and 3 excluded in LDH+TEDgroup. Leaving 78 patients in per protocol analysis.LDH: 5000 U unfractionated heparin preoperatively and x2 for seven days postoperatively.LDH+TED stockings: Same as above. Also stockings until ambulant.Tromboembolic events: DVT, PE and TEBleeding events: Not described.Diagnosis: Radiofibrinogen uptake test on 1,3, 5 and 7 th postoperative day. If positive then confirmed withphlebography.8 patients missing. No intention to treat analysis.AStudy Wille-Jørgensen 1991MethodsParticipantsInterventionsOutcomesNotesAllocation concealmentRCT. Sealed envelopes. Not consecutive. Not blinded. No primary stratification of colorectal patients.Acute abdominal patients. 276 randomized patients. 3 excluded in LDH arm, 15 excluded in LDH+TEDarm and 13 excluded in Dextran+TED arm. Leaving 244 patients in per protocol analysis. Subgroup of51 colorectal patients were distributed with respectively 31%, 33 % and 35% in the three treatment arms.Treatment arm with Dextran+TED were excluded from this analysis. Leaving 33 colorectal patients inanalysis.One arm with dextran is excluded from this analysis. Leaving 160 patients for this analysis. Of these 18 wereexcluded. Subgroup of 33 colorectal patients were distributed with respectively 49 % and 51 % in the tworemaining treatment arms.LDH: 5000 U unfractionated heparin preoperatively and x2 for seven days postoperatively.LDH+TED stockings: Same as above. Also stockings until ambulant.Tromboembolic events: TEBleeding events: Not specified in colorectal patients.Diagnosis: Radiofibrinogen uptake test on 1,3, 5 and 7 th postoperative day. If positive then confirmed withphlebography.18 patients missing. No intention to treat analysis.Balanced distribution of colorectal patients.AHeparins and mechanical methods for thromboprophylaxis in colorectal surgery (Review)Copyright © 2006 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd17

Characteristics of included studies (Continued )Characteristics of excluded studiesBounameaux 1993Browse 1974Comerota 1986 AEllis 1982Gallus 1993Kakkar 1993Mcleod 1995No author 1984Rasmussen 1988Strand 1975Torngren 1982Törngren 1980Colorectal patients not specified. Author contacted. Unable to help.Alternate leg. Not possible to include in meta-analysis.Colorectal patients not specified. Author contacted. Answered that it was not possible to recollect data. Datamore than 15 years old.Colorectal patients not specified. Author contacted. Answered that colorectal data was never specified.Colorectal patients not specified. Author contacted. Answered that it was not possible to recollect data.Double-publication.Possible that some of the patients in the abstract are reused in; Mcleod RS, Geerts WH, Sniderman K et al.Thromboprophylaxis after colorectal surgery - results of a randomized, double-blind comparison of low doseheparin and enoxaparin. Thrombosis and Haemostasis. juni, suppl. 1997:753 no PD3078.May contain patients from other studies.Not possible to identify colorectal patients.Fullfill all criteria but not valid diagnostic methods. Tc-plasmin test.The per protocol analysis operates with 102 surgical procedures in 100 patients. It is not possible to identify thepatient/patients which act as duplicatesHistorical controlgroup.Alternate leg. Not possible to include in meta-analysis.A N A L Y S E SComparison 01. Thromboembolic events (TE). LDH vs. no treatment.Outcome titleNo. ofstudiesNo. ofparticipants Statistical method Effect size01 DVT 4 145 Peto Odds Ratio 95% CI 0.30 [0.14, 0.67]02 PE, no studies 0 0 Peto Odds Ratio 95% CI Not estimable03 DVT and/or PE. Same as in“DVT”.0 0 Peto Odds Ratio 95% CI Not estimableComparison 02. Thromboembolic events (TE). LDH vs. placeboOutcome titleNo. ofstudiesNo. ofparticipants Statistical method Effect size01 DVT 3 114 Peto Odds Ratio 95% CI 0.55 [0.22, 1.36]02 PE 1 19 Peto Odds Ratio 95% CI 0.39 [0.05, 2.91]03 DVT and/or PE. 4 147 Peto Odds Ratio 95% CI 0.46 [0.21, 0.98]Comparison 03. Thromboembolic events (TE). LDH vs. no treatment or placeboOutcome titleNo. ofstudiesNo. ofparticipants Statistical method Effect size01 DVT 7 259 Peto Odds Ratio 95% CI 0.39 [0.22, 0.71]02 PE, same as LDH versus no 0 0 Peto Odds Ratio 95% CI Not estimabletreat/placeboHeparins and mechanical methods for thromboprophylaxis in colorectal surgery (Review)Copyright © 2006 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd18

03 DVT and/or PE. 8 292 Peto Odds Ratio 95% CI 0.35 [0.20, 0.62]Comparison 04. Thromboembolic events (TE). LMWH vs. no treatment.Outcome titleNo. ofstudiesNo. ofparticipants Statistical method Effect size01 DVT 2 338 Peto Odds Ratio 95% CI 0.18 [0.05, 0.59]02 PE 1 303 Peto Odds Ratio 95% CI 0.16 [0.02, 1.62]03 DVT and/or PE. 2 338 Peto Odds Ratio 95% CI 0.18 [0.05, 0.59]Comparison 05. Thromboembolic events (TE). LMWH vs. placeboOutcome titleNo. ofstudiesNo. ofparticipants Statistical method Effect size01 DVT 1 11 Peto Odds Ratio 95% CI 0.11 [0.00, 5.68]02 PE, no studies 0 0 Peto Odds Ratio 95% CI Not estimable03 DVT and/or PE. Same as in“DVT”.0 0 Peto Odds Ratio 95% CI Not estimableComparison 06. Thromboembolic events (TE). LMWH vs. no treatment or placeboOutcome titleNo. ofstudiesNo. ofparticipants Statistical method Effect size01 DVT 3 349 Peto Odds Ratio 95% CI 0.17 [0.05, 0.54]02 PE, same as LMWH versus no 0 0 Peto Odds Ratio 95% CI Not estimabletreatment03 DVT and/or PE, same asLMWH versus no treatment orplacebo / DVT0 0 Peto Odds Ratio 95% CI Not estimableComparison 07. Thromboembolic events (TE). LDH or LMWH vs. no treatment or placeboOutcome titleNo. ofstudiesNo. ofparticipants Statistical method Effect size01 DVT 10 608 Peto Odds Ratio 95% CI 0.33 [0.20, 0.56]02 PE 2 322 Peto Odds Ratio 95% CI 0.27 [0.06, 1.21]03 DVT and/or PE. 11 641 Peto Odds Ratio 95% CI 0.32 [0.20, 0.53]Comparison 08. Thromboembolic events (TE). LDH vs. LMWHOutcome titleNo. ofstudiesNo. ofparticipants Statistical method Effect size01 DVT 3 1177 Peto Odds Ratio 95% CI 1.01 [0.67, 1.52]02 PE 2 942 Peto Odds Ratio 95% CI 0.14 [0.00, 6.82]03 DVT and PE. 4 1183 Peto Odds Ratio 95% CI 1.01 [0.67, 1.52]Heparins and mechanical methods for thromboprophylaxis in colorectal surgery (Review)Copyright © 2006 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd19

Comparison 09. Thromboembolic events (TE). LDH versus IPCOutcome titleNo. of No. ofstudies participants Statistical method Effect size01 DVT 1 5 Peto Odds Ratio 95% CI Not estimable02 PE, no studies 0 0 Peto Odds Ratio 95% CI Not estimable03 DVT and/or PE. Same as in“DVT”.0 0 Peto Odds Ratio 95% CI Not estimableComparison 10. Thromboembolic events (TE). LDH vs. LDH+TEDOutcome titleNo. of No. ofstudies participants Statistical method Effect size01 DVT 2 111 Peto Odds Ratio 95% CI 4.62 [1.33, 16.01]02 PE 2 111 Peto Odds Ratio 95% CI 3.01 [0.64, 14.16]03 DVT and/or PE. 2 111 Peto Odds Ratio 95% CI 4.17 [1.37, 12.70]Comparison 11. Thromboembolic events (TE). LDH vs. TED + IPCOutcome titleNo. of No. ofstudies participants Statistical method Effect size01 DVT 1 23 Peto Odds Ratio 95% CI 9.97 [0.93, 107.33]02 PE, no studies 0 0 Peto Odds Ratio 95% CI Not estimable03 DVT and/or PE. Same as in“DVT”.0 0 Peto Odds Ratio 95% CI Not estimableComparison 12. Thromboembolic events (TE). IPC vs. no treatmentOutcome titleNo. of No. ofstudies participants Statistical method Effect size01 DVT 1 24 Peto Odds Ratio 95% CI 0.57 [0.03, 10.69]02 PE, no studies 0 0 Peto Odds Ratio 95% CI Not estimable03 DVT and/or PE. Same as in“DVT”.0 0 Peto Odds Ratio 95% CI Not estimableMedical Subject Headings (MeSH)I N D E XT E R M SAnticoagulants [ ∗ therapeutic use]; Bandages; ∗ Colorectal Surgery; Confidence Intervals; Heparin [ ∗ therapeutic use]; Heparin, Low-Molecular-Weight [therapeutic use]; Odds Ratio; Postoperative Complications [ ∗ prevention & control]; Pulmonary Embolism[ ∗ prevention & control]; Venous Thrombosis [ ∗ prevention & control]MeSH check wordsHumansTitleAuthorsContribution of author(s)C O V E RS H E E THeparins and mechanical methods for thromboprophylaxis in colorectal surgeryWille-Jørgensen P, Rasmussen MS, Andersen BR, Borly LPeer Wille-Jørgensen came with the idea, structured the work, extracted data and made thefinal manuscript. Bettina R. Andersen and Morten S. Rasmussen did the literature-searchHeparins and mechanical methods for thromboprophylaxis in colorectal surgery (Review)Copyright © 2006 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd20

and extracted data. Lars Borly retrieved extra data from authors, made the data-entry, andthe analysis. Morten S. Rasmussen and Lisbeth S. G. Mathiesen did the literature searchand latest update. Peer Wille-Jørgensen did the final editing work.Issue protocol first published 1998/3Review first published 2001/3Date of most recent amendment 15 August 2005Date of most recentSUBSTANTIVE amendment28 August 2003What’s New Review title changed in agreement with author (19/8/99)New co-author, Lars Borly (24/8/99)Revised after peer-reviewing (8/1/2001)The reference McLeod 2001 substitutes the former abstract McLeod 1997.Updated (01/09/2003)Date new studies sought butnone found30 April 2003Date new studies found but notyet included/excludedInformation not supplied by authorDate new studies found andincluded/excludedInformation not supplied by authorDate authors’ conclusionssection amendedContact addressDOICochrane Library numberEditorial groupEditorial group codeInformation not supplied by authorPeer Wille-JørgensenConsultant SurgeonDepartment of Surgical Gastroenterology KH:S Bispebjerg HospitalBispebjerg BakkeCopenhagen NVDK-2400DENMARKE-mail: pwj01@bbh.hosp.dkTel: +45 3531 308610.1002/14651858.CD001217CD001217Cochrane Colorectal Cancer GroupHM-COLOCAHeparins and mechanical methods for thromboprophylaxis in colorectal surgery (Review)Copyright © 2006 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd21

G R A P H S A N D O T H E R T A B L E SAnalysis 01.01. Comparison 01 Thromboembolic events (TE). LDH vs. no treatment., Outcome 01 DVTReview: Heparins and mechanical methods for thromboprophylaxis in colorectal surgeryComparison: 01 Thromboembolic events (TE). LDH vs. no treatment.Outcome: 01 DVTStudy LDH No treatment Peto Odds Ratio Weight Peto Odds Ration/N n/N 95% CI (%) 95% CIGallus 1976 5/44 13/46 58.4 0.35 [ 0.13, 0.98 ]Joffe 1976 2/8 3/6 13.6 0.36 [ 0.04, 3.06 ]x Kosir 1996 0/3 0/7 0.0 Not estimableRem 1975 4/19 7/12 27.9 0.21 [ 0.05, 0.91 ]Total (95% CI) 74 71 100.0 0.30 [ 0.14, 0.67 ]Total events: 11 (LDH), 23 (No treatment)Test for heterogeneity chi-square=0.36 df=2 p=0.83 I² =0.0%Test for overall effect z=2.97 p=0.0030.1 0.2 0.5 1 2 5 10Favours treatmentFavours controlAnalysis 01.02.Review:Comparison:Outcome:Comparison 01 Thromboembolic events (TE). LDH vs. no treatment., Outcome 02 PE, nostudiesHeparins and mechanical methods for thromboprophylaxis in colorectal surgery01 Thromboembolic events (TE). LDH vs. no treatment.02 PE, no studiesStudy LDH No treatment Peto Odds Ratio Weight Peto Odds Ration/N n/N 95% CI (%) 95% CITotal (95% CI) 0 0 0.0 Not estimableTotal events: 0 (LDH), 0 (No treatment)Test for heterogeneity: not applicableTest for overall effect: not applicable0.1 0.2 0.5 1 2 5 10Favours treatmentFavours controlHeparins and mechanical methods for thromboprophylaxis in colorectal surgery (Review)Copyright © 2006 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd22

Analysis 01.03.Review:Comparison:Outcome:Comparison 01 Thromboembolic events (TE). LDH vs. no treatment., Outcome 03 DVTand/or PE. Same as in “DVT”.Heparins and mechanical methods for thromboprophylaxis in colorectal surgery01 Thromboembolic events (TE). LDH vs. no treatment.03 DVT and/or PE. Same as in ”DVT”.Study LDH No treatment Peto Odds Ratio Weight Peto Odds Ration/N n/N 95% CI (%) 95% CITotal (95% CI) 0 0 0.0 Not estimableTotal events: 0 (LDH), 0 (No treatment)Test for heterogeneity: not applicableTest for overall effect: not applicable0.1 0.2 0.5 1 2 5 10Favours treatmentFavours controlAnalysis 02.01. Comparison 02 Thromboembolic events (TE). LDH vs. placebo, Outcome 01 DVTReview: Heparins and mechanical methods for thromboprophylaxis in colorectal surgeryComparison: 02 Thromboembolic events (TE). LDH vs. placeboOutcome: 01 DVTStudy LDH Placebo Peto Odds Ratio Weight Peto Odds Ration/N n/N 95% CI (%) 95% CICovey 1975 3/9 1/11 17.6 4.22 [ 0.49, 36.09 ]Lahnborg 1974 0/11 2/8 9.7 0.08 [ 0.00, 1.45 ]Torngren 1978 7/41 11/34 72.6 0.44 [ 0.15, 1.26 ]Total (95% CI) 61 53 100.0 0.55 [ 0.22, 1.36 ]Total events: 10 (LDH), 14 (Placebo)Test for heterogeneity chi-square=5.33 df=2 p=0.07 I² =62.5%Test for overall effect z=1.29 p=0.20.1 0.2 0.5 1 2 5 10Favours treatmentFavours controlHeparins and mechanical methods for thromboprophylaxis in colorectal surgery (Review)Copyright © 2006 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd23

Analysis 02.02. Comparison 02 Thromboembolic events (TE). LDH vs. placebo, Outcome 02 PEReview: Heparins and mechanical methods for thromboprophylaxis in colorectal surgeryComparison: 02 Thromboembolic events (TE). LDH vs. placeboOutcome: 02 PEStudy LDH Placebo Peto Odds Ratio Weight Peto Odds Ration/N n/N 95% CI (%) 95% CILahnborg 1974 2/11 3/8 100.0 0.39 [ 0.05, 2.91 ]Total (95% CI) 11 8 100.0 0.39 [ 0.05, 2.91 ]Total events: 2 (LDH), 3 (Placebo)Test for heterogeneity: not applicableTest for overall effect z=0.92 p=0.40.1 0.2 0.5 1 2 5 10Favours treatmentFavours controlAnalysis 02.03. Comparison 02 Thromboembolic events (TE). LDH vs. placebo, Outcome 03 DVT and/or PE.Review: Heparins and mechanical methods for thromboprophylaxis in colorectal surgeryComparison: 02 Thromboembolic events (TE). LDH vs. placeboOutcome: 03 DVT and/or PE.Study LDH Placebo Peto Odds Ratio Weight Peto Odds Ration/N n/N 95% CI (%) 95% CICovey 1975 3/9 1/11 12.9 4.22 [ 0.49, 36.09 ]Lahnborg 1974 2/11 3/8 14.7 0.39 [ 0.05, 2.91 ]Negus 1980 0/14 6/19 19.2 0.13 [ 0.02, 0.74 ]Torngren 1978 7/41 11/34 53.2 0.44 [ 0.15, 1.26 ]Total (95% CI) 75 72 100.0 0.46 [ 0.21, 0.98 ]Total events: 12 (LDH), 21 (Placebo)Test for heterogeneity chi-square=6.16 df=3 p=0.10 I² =51.3%Test for overall effect z=2.00 p=0.050.1 0.2 0.5 1 2 5 10Favours treatmentFavours controlHeparins and mechanical methods for thromboprophylaxis in colorectal surgery (Review)Copyright © 2006 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd24

Analysis 03.01. Comparison 03 Thromboembolic events (TE). LDH vs. no treatment or placebo, Outcome 01DVTReview:Comparison:Outcome:Heparins and mechanical methods for thromboprophylaxis in colorectal surgery03 Thromboembolic events (TE). LDH vs. no treatment or placebo01 DVTStudy LDH No treat./placebo Peto Odds Ratio Weight Peto Odds Ration/N n/N 95% CI (%) 95% CICovey 1975 3/9 1/11 7.6 4.22 [ 0.49, 36.09 ]Gallus 1976 5/44 13/46 33.2 0.35 [ 0.13, 0.98 ]Joffe 1976 2/8 3/6 7.7 0.36 [ 0.04, 3.06 ]x Kosir 1996 0/3 0/7 0.0 Not estimableLahnborg 1974 0/11 2/8 4.2 0.08 [ 0.00, 1.45 ]Rem 1975 4/19 7/12 15.9 0.21 [ 0.05, 0.91 ]Torngren 1978 7/41 11/34 31.4 0.44 [ 0.15, 1.26 ]Total (95% CI) 135 124 100.0 0.39 [ 0.22, 0.71 ]Total events: 21 (LDH), 37 (No treat./placebo)Test for heterogeneity chi-square=6.65 df=5 p=0.25 I² =24.8%Test for overall effect z=3.08 p=0.0020.1 0.2 0.5 1 2 5 10Favours treatmentFavours controlAnalysis 03.02. Comparison 03 Thromboembolic events (TE). LDH vs. no treatment or placebo, Outcome 02PE, same as LDH versus no treat/placeboReview:Comparison:Outcome:Heparins and mechanical methods for thromboprophylaxis in colorectal surgery03 Thromboembolic events (TE). LDH vs. no treatment or placebo02 PE, same as LDH versus no treat/placeboStudy LDH No treat/placebo Peto Odds Ratio Weight Peto Odds Ration/N n/N 95% CI (%) 95% CITotal (95% CI) 0 0 0.0 Not estimableTotal events: 0 (LDH), 0 (No treat/placebo)Test for heterogeneity: not applicableTest for overall effect: not applicable0.1 0.2 0.5 1 2 5 10Favours treatmentFavours controlHeparins and mechanical methods for thromboprophylaxis in colorectal surgery (Review)Copyright © 2006 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd25

Analysis 03.03. Comparison 03 Thromboembolic events (TE). LDH vs. no treatment or placebo, Outcome 03DVT and/or PE.Review:Comparison:Outcome:Heparins and mechanical methods for thromboprophylaxis in colorectal surgery03 Thromboembolic events (TE). LDH vs. no treatment or placebo03 DVT and/or PE.Study LDH No treat/placebo Peto Odds Ratio Weight Peto Odds Ration/N n/N 95% CI (%) 95% CICovey 1975 3/9 1/11 6.8 4.22 [ 0.49, 36.09 ]Gallus 1976 5/44 13/46 29.8 0.35 [ 0.13, 0.98 ]Joffe 1976 2/8 3/6 7.0 0.36 [ 0.04, 3.06 ]x Kosir 1996 0/3 0/7 0.0 Not estimableLahnborg 1974 0/11 2/8 3.8 0.08 [ 0.00, 1.45 ]Negus 1980 0/14 6/19 10.1 0.13 [ 0.02, 0.74 ]Rem 1975 4/19 7/12 14.3 0.21 [ 0.05, 0.91 ]Torngren 1978 7/41 11/34 28.2 0.44 [ 0.15, 1.26 ]Total (95% CI) 149 143 100.0 0.35 [ 0.20, 0.62 ]Total events: 21 (LDH), 43 (No treat/placebo)Test for heterogeneity chi-square=8.07 df=6 p=0.23 I² =25.6%Test for overall effect z=3.65 p=0.00030.1 0.2 0.5 1 2 5 10Favours treatmentFavours controlAnalysis 04.01. Comparison 04 Thromboembolic events (TE). LMWH vs. no treatment., Outcome 01 DVTReview: Heparins and mechanical methods for thromboprophylaxis in colorectal surgeryComparison: 04 Thromboembolic events (TE). LMWH vs. no treatment.Outcome: 01 DVTStudy LMWH No treatment Peto Odds Ratio Weight Peto Odds Ration/N n/N 95% CI (%) 95% CIHo 1999 0/134 5/169 45.8 0.16 [ 0.03, 0.96 ]Maressi 1993 1/17 6/18 54.2 0.19 [ 0.04, 0.97 ]Total (95% CI) 151 187 100.0 0.18 [ 0.05, 0.59 ]Total events: 1 (LMWH), 11 (No treatment)Test for heterogeneity chi-square=0.01 df=1 p=0.90 I² =0.0%Test for overall effect z=2.83 p=0.0050.1 0.2 0.5 1 2 5 10Favours treatmentFavours controlHeparins and mechanical methods for thromboprophylaxis in colorectal surgery (Review)Copyright © 2006 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd26

Analysis 04.02. Comparison 04 Thromboembolic events (TE). LMWH vs. no treatment., Outcome 02 PEReview: Heparins and mechanical methods for thromboprophylaxis in colorectal surgeryComparison: 04 Thromboembolic events (TE). LMWH vs. no treatment.Outcome: 02 PEStudy LMWH No treatment Peto Odds Ratio Weight Peto Odds Ration/N n/N 95% CI (%) 95% CIHo 1999 0/134 3/169 100.0 0.16 [ 0.02, 1.62 ]Total (95% CI) 134 169 100.0 0.16 [ 0.02, 1.62 ]Total events: 0 (LMWH), 3 (No treatment)Test for heterogeneity: not applicableTest for overall effect z=1.55 p=0.10.1 0.2 0.5 1 2 5 10Favours treatmentFavours controlAnalysis 04.03.Review:Comparison:Comparison 04 Thromboembolic events (TE). LMWH vs. no treatment., Outcome 03 DVTand/or PE.Heparins and mechanical methods for thromboprophylaxis in colorectal surgery04 Thromboembolic events (TE). LMWH vs. no treatment.Outcome: 03 DVT and/or PE.Study LMWH No treatment Peto Odds Ratio Weight Peto Odds Ration/N n/N 95% CI (%) 95% CIHo 1999 0/134 5/169 45.8 0.16 [ 0.03, 0.96 ]Maressi 1993 1/17 6/18 54.2 0.19 [ 0.04, 0.97 ]Total (95% CI) 151 187 100.0 0.18 [ 0.05, 0.59 ]Total events: 1 (LMWH), 11 (No treatment)Test for heterogeneity chi-square=0.01 df=1 p=0.90 I² =0.0%Test for overall effect z=2.83 p=0.0050.1 0.2 0.5 1 2 5 10Favours treatmentFavours controlHeparins and mechanical methods for thromboprophylaxis in colorectal surgery (Review)Copyright © 2006 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd27

Analysis 05.01. Comparison 05 Thromboembolic events (TE). LMWH vs. placebo, Outcome 01 DVTReview: Heparins and mechanical methods for thromboprophylaxis in colorectal surgeryComparison: 05 Thromboembolic events (TE). LMWH vs. placeboOutcome: 01 DVTStudy LMWH Placebo Peto Odds Ratio Weight Peto Odds Ration/N n/N 95% CI (%) 95% CIValle 1988 0/6 1/5 100.0 0.11 [ 0.00, 5.68 ]Total (95% CI) 6 5 100.0 0.11 [ 0.00, 5.68 ]Total events: 0 (LMWH), 1 (Placebo)Test for heterogeneity: not applicableTest for overall effect z=1.10 p=0.30.1 0.2 0.5 1 2 5 10Favours treatmentFavours controlAnalysis 05.02. Comparison 05 Thromboembolic events (TE). LMWH vs. placebo, Outcome 02 PE, no studiesReview: Heparins and mechanical methods for thromboprophylaxis in colorectal surgeryComparison: 05 Thromboembolic events (TE). LMWH vs. placeboOutcome: 02 PE, no studiesStudy LMWH Placebo Peto Odds Ratio Weight Peto Odds Ration/N n/N 95% CI (%) 95% CITotal (95% CI) 0 0 0.0 Not estimableTotal events: 0 (LMWH), 0 (Placebo)Test for heterogeneity: not applicableTest for overall effect: not applicable0.1 0.2 0.5 1 2 5 10Favours treatmentFavours controlAnalysis 05.03.Review:Comparison:Outcome:Comparison 05 Thromboembolic events (TE). LMWH vs. placebo, Outcome 03 DVT and/orPE. Same as in “DVT”.Heparins and mechanical methods for thromboprophylaxis in colorectal surgery05 Thromboembolic events (TE). LMWH vs. placebo03 DVT and/or PE. Same as in ”DVT”.Study LMWH Placebo Peto Odds Ratio Weight Peto Odds Ration/N n/N 95% CI (%) 95% CITotal (95% CI) 0 0 0.0 Not estimableTotal events: 0 (LMWH), 0 (Placebo)Test for heterogeneity: not applicableTest for overall effect: not applicable0.1 0.2 0.5 1 2 5 10Favours treatmentFavours controlHeparins and mechanical methods for thromboprophylaxis in colorectal surgery (Review)Copyright © 2006 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd28

Analysis 06.01.Review:Comparison:Outcome:Comparison 06 Thromboembolic events (TE). LMWH vs. no treatment or placebo, Outcome01 DVTHeparins and mechanical methods for thromboprophylaxis in colorectal surgery06 Thromboembolic events (TE). LMWH vs. no treatment or placebo01 DVTStudy LMWH No treat/placebo Peto Odds Ratio Weight Peto Odds Ration/N n/N 95% CI (%) 95% CIHo 1999 0/134 5/169 41.9 0.16 [ 0.03, 0.96 ]Maressi 1993 1/17 6/18 49.6 0.19 [ 0.04, 0.97 ]Valle 1988 0/6 1/5 8.5 0.11 [ 0.00, 5.68 ]Total (95% CI) 157 192 100.0 0.17 [ 0.05, 0.54 ]Total events: 1 (LMWH), 12 (No treat/placebo)Test for heterogeneity chi-square=0.06 df=2 p=0.97 I² =0.0%Test for overall effect z=3.03 p=0.0020.1 0.2 0.5 1 2 5 10Favours treatmentFavours controlAnalysis 06.02.Review:Comparison:Outcome:Comparison 06 Thromboembolic events (TE). LMWH vs. no treatment or placebo, Outcome02 PE, same as LMWH versus no treatmentHeparins and mechanical methods for thromboprophylaxis in colorectal surgery06 Thromboembolic events (TE). LMWH vs. no treatment or placebo02 PE, same as LMWH versus no treatmentStudy LMWH No treatment Peto Odds Ratio Weight Peto Odds Ration/N n/N 95% CI (%) 95% CITotal (95% CI) 0 0 0.0 Not estimableTotal events: 0 (LMWH), 0 (No treatment)Test for heterogeneity: not applicableTest for overall effect: not applicable0.1 0.2 0.5 1 2 5 10Favours treatmentFavours controlHeparins and mechanical methods for thromboprophylaxis in colorectal surgery (Review)Copyright © 2006 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd29

Analysis 06.03.Review:Comparison:Outcome:Comparison 06 Thromboembolic events (TE). LMWH vs. no treatment or placebo, Outcome03 DVT and/or PE, same as LMWH versus no treatment or placebo / DVTHeparins and mechanical methods for thromboprophylaxis in colorectal surgery06 Thromboembolic events (TE). LMWH vs. no treatment or placebo03 DVT and/or PE, same as LMWH versus no treatment or placebo / DVTStudy LMWH No treatment Peto Odds Ratio Weight Peto Odds Ration/N n/N 95% CI (%) 95% CITotal (95% CI) 0 0 0.0 Not estimableTotal events: 0 (LMWH), 0 (No treatment)Test for heterogeneity: not applicableTest for overall effect: not applicable0.1 0.2 0.5 1 2 5 10Favours treatmentFavours controlAnalysis 07.01.Review:Comparison:Outcome:Comparison 07 Thromboembolic events (TE). LDH or LMWH vs. no treatment or placebo,Outcome 01 DVTHeparins and mechanical methods for thromboprophylaxis in colorectal surgery07 Thromboembolic events (TE). LDH or LMWH vs. no treatment or placebo01 DVTStudy LDH or LMWH No treat. and Placeb Peto Odds Ratio Weight Peto Odds Ration/N n/N 95% CI (%) 95% CICovey 1975 3/9 1/11 6.0 4.22 [ 0.49, 36.09 ]Gallus 1976 5/44 13/46 26.3 0.35 [ 0.13, 0.98 ]Ho 1999 0/134 5/169 8.8 0.16 [ 0.03, 0.96 ]Joffe 1976 2/8 3/6 6.1 0.36 [ 0.04, 3.06 ]x Kosir 1996 0/3 0/7 0.0 Not estimableLahnborg 1974 0/11 2/8 3.3 0.08 [ 0.00, 1.45 ]Maressi 1993 1/17 6/18 10.4 0.19 [ 0.04, 0.97 ]Rem 1975 4/19 7/12 12.6 0.21 [ 0.05, 0.91 ]Torngren 1978 7/41 11/34 24.8 0.44 [ 0.15, 1.26 ]Valle 1988 0/6 1/5 1.8 0.11 [ 0.00, 5.68 ]Total (95% CI) 292 316 100.0 0.33 [ 0.20, 0.56 ]Total events: 22 (LDH or LMWH), 49 (No treat. and Placeb)Test for heterogeneity chi-square=8.35 df=8 p=0.40 I² =4.2%Test for overall effect z=4.12 p=0.000040.1 0.2 0.5 1 2 5 10Favours treatmentFavours controlHeparins and mechanical methods for thromboprophylaxis in colorectal surgery (Review)Copyright © 2006 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd30

Analysis 07.02.Review:Comparison:Outcome:Comparison 07 Thromboembolic events (TE). LDH or LMWH vs. no treatment or placebo,Outcome 02 PEHeparins and mechanical methods for thromboprophylaxis in colorectal surgery07 Thromboembolic events (TE). LDH or LMWH vs. no treatment or placebo02 PEStudy LDH or LMWH No treat/placebo Peto Odds Ratio Weight Peto Odds Ration/N n/N 95% CI (%) 95% CIHo 1999 0/134 3/169 43.7 0.16 [ 0.02, 1.62 ]Lahnborg 1974 2/11 3/8 56.3 0.39 [ 0.05, 2.91 ]Total (95% CI) 145 177 100.0 0.27 [ 0.06, 1.21 ]Total events: 2 (LDH or LMWH), 6 (No treat/placebo)Test for heterogeneity chi-square=0.31 df=1 p=0.58 I² =0.0%Test for overall effect z=1.71 p=0.090.1 0.2 0.5 1 2 5 10Favours treatmentFavours controlAnalysis 07.03.Review:Comparison:Outcome:Comparison 07 Thromboembolic events (TE). LDH or LMWH vs. no treatment or placebo,Outcome 03 DVT and/or PE.Heparins and mechanical methods for thromboprophylaxis in colorectal surgery07 Thromboembolic events (TE). LDH or LMWH vs. no treatment or placebo03 DVT and/or PE.Study LDH or LMWH No treat/placebo Peto Odds Ratio Weight Peto Odds Ration/N n/N 95% CI (%) 95% CICovey 1975 3/9 1/11 5.3 4.22 [ 0.49, 36.09 ]Gallus 1976 5/44 13/46 23.3 0.35 [ 0.13, 0.98 ]Ho 1999 0/134 5/169 7.8 0.16 [ 0.03, 0.96 ]Joffe 1976 2/8 3/6 5.4 0.36 [ 0.04, 3.06 ]x Kosir 1996 0/3 0/7 0.0 Not estimableLahnborg 1974 2/11 3/8 6.1 0.39 [ 0.05, 2.91 ]Maressi 1993 1/17 6/18 9.2 0.19 [ 0.04, 0.97 ]Negus 1980 0/14 6/19 7.9 0.13 [ 0.02, 0.74 ]Rem 1975 4/19 7/12 11.2 0.21 [ 0.05, 0.91 ]Torngren 1978 7/41 11/34 22.0 0.44 [ 0.15, 1.26 ]Valle 1988 0/6 1/5 1.6 0.11 [ 0.00, 5.68 ]Total (95% CI) 306 335 100.0 0.32 [ 0.20, 0.53 ]Total events: 24 (LDH or LMWH), 56 (No treat/placebo)Test for heterogeneity chi-square=8.58 df=9 p=0.48 I² =0.0%Test for overall effect z=4.47 p

Analysis 08.01. Comparison 08 Thromboembolic events (TE). LDH vs. LMWH, Outcome 01 DVTReview: Heparins and mechanical methods for thromboprophylaxis in colorectal surgeryComparison: 08 Thromboembolic events (TE). LDH vs. LMWHOutcome: 01 DVTStudy LDH LMWH Peto Odds Ratio Weight Peto Odds Ration/N n/N 95% CI (%) 95% CIKoppenhagen 1992 6/92 6/103 12.1 1.13 [ 0.35, 3.62 ]Mcleod 2001 44/468 44/468 85.8 1.00 [ 0.64, 1.55 ]Onarheim 1986 1/24 1/22 2.1 0.91 [ 0.06, 15.13 ]Total (95% CI) 584 593 100.0 1.01 [ 0.67, 1.52 ]Total events: 51 (LDH), 51 (LMWH)Test for heterogeneity chi-square=0.04 df=2 p=0.98 I² =0.0%Test for overall effect z=0.06 p=10.1 0.2 0.5 1 2 5 10Favours treatmentFavours controlAnalysis 08.02. Comparison 08 Thromboembolic events (TE). LDH vs. LMWH, Outcome 02 PEReview: Heparins and mechanical methods for thromboprophylaxis in colorectal surgeryComparison: 08 Thromboembolic events (TE). LDH vs. LMWHOutcome: 02 PEStudy LDH LMWH Peto Odds Ratio Weight Peto Odds Ration/N n/N 95% CI (%) 95% CIx Fricker 1988 0/2 0/4 0.0 Not estimableMcleod 2001 0/468 1/468 100.0 0.14 [ 0.00, 6.82 ]Total (95% CI) 470 472 100.0 0.14 [ 0.00, 6.82 ]Total events: 0 (LDH), 1 (LMWH)Test for heterogeneity: not applicableTest for overall effect z=1.00 p=0.30.1 0.2 0.5 1 2 5 10Favours treatmentFavours controlHeparins and mechanical methods for thromboprophylaxis in colorectal surgery (Review)Copyright © 2006 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd32

Analysis 08.03. Comparison 08 Thromboembolic events (TE). LDH vs. LMWH, Outcome 03 DVT and PE.Review: Heparins and mechanical methods for thromboprophylaxis in colorectal surgeryComparison: 08 Thromboembolic events (TE). LDH vs. LMWHOutcome: 03 DVT and PE.Study LDH LMWH Peto Odds Ratio Weight Peto Odds Ration/N n/N 95% CI (%) 95% CIx Fricker 1988 0/2 0/4 0.0 Not estimableKoppenhagen 1992 6/92 6/103 12.1 1.13 [ 0.35, 3.62 ]Mcleod 2001 44/468 44/468 85.8 1.00 [ 0.64, 1.55 ]Onarheim 1986 1/24 1/22 2.1 0.91 [ 0.06, 15.13 ]Total (95% CI) 586 597 100.0 1.01 [ 0.67, 1.52 ]Total events: 51 (LDH), 51 (LMWH)Test for heterogeneity chi-square=0.04 df=2 p=0.98 I² =0.0%Test for overall effect z=0.06 p=10.1 0.2 0.5 1 2 5 10Favours treatmentFavours controlAnalysis 09.01. Comparison 09 Thromboembolic events (TE). LDH versus IPC, Outcome 01 DVTReview: Heparins and mechanical methods for thromboprophylaxis in colorectal surgeryComparison: 09 Thromboembolic events (TE). LDH versus IPCOutcome: 01 DVTStudy LDH Inter. compre. Peto Odds Ratio Weight Peto Odds Ration/N n/N 95% CI (%) 95% CIx Kosir 1996 0/3 0/2 0.0 Not estimableTotal (95% CI) 3 2 0.0 Not estimableTotal events: 0 (LDH), 0 (Inter. compre.)Test for heterogeneity: not applicableTest for overall effect: not applicable0.1 0.2 0.5 1 2 5 10Favours treatmentFavours controlHeparins and mechanical methods for thromboprophylaxis in colorectal surgery (Review)Copyright © 2006 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd33

Analysis 09.02. Comparison 09 Thromboembolic events (TE). LDH versus IPC, Outcome 02 PE, no studiesReview: Heparins and mechanical methods for thromboprophylaxis in colorectal surgeryComparison: 09 Thromboembolic events (TE). LDH versus IPCOutcome: 02 PE, no studiesStudy LDH Inter. compre. Peto Odds Ratio Weight Peto Odds Ration/N n/N 95% CI (%) 95% CITotal (95% CI) 0 0 0.0 Not estimableTotal events: 0 (LDH), 0 (Inter. compre.)Test for heterogeneity: not applicableTest for overall effect: not applicable0.1 0.2 0.5 1 2 5 10Favours treatmentFavours controlAnalysis 09.03.Review:Comparison:Outcome:Comparison 09 Thromboembolic events (TE). LDH versus IPC, Outcome 03 DVT and/or PE.Same as in “DVT”.Heparins and mechanical methods for thromboprophylaxis in colorectal surgery09 Thromboembolic events (TE). LDH versus IPC03 DVT and/or PE. Same as in ”DVT”.Study LDH IPC Peto Odds Ratio Weight Peto Odds Ration/N n/N 95% CI (%) 95% CITotal (95% CI) 0 0 0.0 Not estimableTotal events: 0 (LDH), 0 (IPC)Test for heterogeneity: not applicableTest for overall effect: not applicable0.1 0.2 0.5 1 2 5 10Favours treatmentFavours controlAnalysis 10.01. Comparison 10 Thromboembolic events (TE). LDH vs. LDH+TED, Outcome 01 DVTReview: Heparins and mechanical methods for thromboprophylaxis in colorectal surgeryComparison: 10 Thromboembolic events (TE). LDH vs. LDH+TEDOutcome: 01 DVTStudy LDH LDH+TED stockings Peto Odds Ratio Weight Peto Odds Ration/N n/N 95% CI (%) 95% CIWille-Jørgensen 1986 5/36 1/42 56.1 4.95 [ 0.94, 26.04 ]Wille-Jørgensen 1991 4/16 1/17 43.9 4.23 [ 0.65, 27.58 ]Total (95% CI) 52 59 100.0 4.62 [ 1.33, 16.01 ]Total events: 9 (LDH), 2 (LDH+TED stockings)Test for heterogeneity chi-square=0.02 df=1 p=0.90 I² =0.0%Test for overall effect z=2.41 p=0.020.1 0.2 0.5 1 2 5 10Favours treatmentFavours controlHeparins and mechanical methods for thromboprophylaxis in colorectal surgery (Review)Copyright © 2006 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd34

Analysis 10.02. Comparison 10 Thromboembolic events (TE). LDH vs. LDH+TED, Outcome 02 PEReview: Heparins and mechanical methods for thromboprophylaxis in colorectal surgeryComparison: 10 Thromboembolic events (TE). LDH vs. LDH+TEDOutcome: 02 PEStudy LDH LDH+TED stockings Peto Odds Ratio Weight Peto Odds Ration/N n/N 95% CI (%) 95% CIWille-Jørgensen 1986 5/36 2/42 100.0 3.01 [ 0.64, 14.16 ]x Wille-Jørgensen 1991 0/16 0/17 0.0 Not estimableTotal (95% CI) 52 59 100.0 3.01 [ 0.64, 14.16 ]Total events: 5 (LDH), 2 (LDH+TED stockings)Test for heterogeneity: not applicableTest for overall effect z=1.40 p=0.20.1 0.2 0.5 1 2 5 10Favours treatmentFavours controlAnalysis 10.03.Review:Comparison 10 Thromboembolic events (TE). LDH vs. LDH+TED, Outcome 03 DVT and/orPE.Heparins and mechanical methods for thromboprophylaxis in colorectal surgeryComparison: 10 Thromboembolic events (TE). LDH vs. LDH+TEDOutcome:03 DVT and/or PE.Study LDH LDH+TED stockings Peto Odds Ratio Weight Peto Odds Ration/N n/N 95% CI (%) 95% CIWille-Jørgensen 1986 7/36 2/42 64.7 4.14 [ 1.04, 16.52 ]Wille-Jørgensen 1991 4/16 1/17 35.3 4.23 [ 0.65, 27.58 ]Total (95% CI) 52 59 100.0 4.17 [ 1.37, 12.70 ]Total events: 11 (LDH), 3 (LDH+TED stockings)Test for heterogeneity chi-square=0.00 df=1 p=0.99 I² =0.0%Test for overall effect z=2.51 p=0.010.1 0.2 0.5 1 2 5 10Favours treatmentFavours controlHeparins and mechanical methods for thromboprophylaxis in colorectal surgery (Review)Copyright © 2006 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd35

Analysis 11.01. Comparison 11 Thromboembolic events (TE). LDH vs. TED + IPC, Outcome 01 DVTReview: Heparins and mechanical methods for thromboprophylaxis in colorectal surgeryComparison: 11 Thromboembolic events (TE). LDH vs. TED + IPCOutcome: 01 DVTStudy LDH TED+ IPC Peto Odds Ratio Weight Peto Odds Ration/N n/N 95% CI (%) 95% CINicolaides 1983 3/11 0/12 100.0 9.97 [ 0.93, 107.33 ]Total (95% CI) 11 12 100.0 9.97 [ 0.93, 107.33 ]Total events: 3 (LDH), 0 (TED+ IPC)Test for heterogeneity: not applicableTest for overall effect z=1.90 p=0.060.1 0.2 0.5 1 2 5 10Favours treatmentFavours controlAnalysis 11.02.Review:Comparison:Outcome:Comparison 11 Thromboembolic events (TE). LDH vs. TED + IPC, Outcome 02 PE, nostudiesHeparins and mechanical methods for thromboprophylaxis in colorectal surgery11 Thromboembolic events (TE). LDH vs. TED + IPC02 PE, no studiesStudy LDH TED stockings Peto Odds Ratio Weight Peto Odds Ration/N n/N 95% CI (%) 95% CITotal (95% CI) 0 0 0.0 Not estimableTotal events: 0 (LDH), 0 (TED stockings)Test for heterogeneity: not applicableTest for overall effect: not applicable0.1 0.2 0.5 1 2 5 10Favours treatmentFavours controlAnalysis 11.03.Review:Comparison:Outcome:Comparison 11 Thromboembolic events (TE). LDH vs. TED + IPC, Outcome 03 DVT and/orPE. Same as in “DVT”.Heparins and mechanical methods for thromboprophylaxis in colorectal surgery11 Thromboembolic events (TE). LDH vs. TED + IPC03 DVT and/or PE. Same as in ”DVT”.Study LDH TED stockings + IPC Peto Odds Ratio Weight Peto Odds Ration/N n/N 95% CI (%) 95% CITotal (95% CI) 0 0 0.0 Not estimableTotal events: 0 (LDH), 0 (TED stockings + IPC)Test for heterogeneity: not applicableTest for overall effect: not applicable0.1 0.2 0.5 1 2 5 10Favours treatmentFavours controlHeparins and mechanical methods for thromboprophylaxis in colorectal surgery (Review)Copyright © 2006 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd36

Analysis 12.01. Comparison 12 Thromboembolic events (TE). IPC vs. no treatment, Outcome 01 DVTReview: Heparins and mechanical methods for thromboprophylaxis in colorectal surgeryComparison: 12 Thromboembolic events (TE). IPC vs. no treatmentOutcome: 01 DVTStudy Intermittent compres No treatment Peto Odds Ratio Weight Peto Odds Ration/N n/N 95% CI (%) 95% CIButson 1981 1/15 1/9 100.0 0.57 [ 0.03, 10.69 ]Total (95% CI) 15 9 100.0 0.57 [ 0.03, 10.69 ]Total events: 1 (Intermittent compres), 1 (No treatment)Test for heterogeneity: not applicableTest for overall effect z=0.37 p=0.70.1 0.2 0.5 1 2 5 10Favours treatmentFavours controlAnalysis 12.02.Review:Comparison:Outcome:Comparison 12 Thromboembolic events (TE). IPC vs. no treatment, Outcome 02 PE, nostudiesHeparins and mechanical methods for thromboprophylaxis in colorectal surgery12 Thromboembolic events (TE). IPC vs. no treatment02 PE, no studiesStudy IPC No treatment Peto Odds Ratio Weight Peto Odds Ration/N n/N 95% CI (%) 95% CITotal (95% CI) 0 0 0.0 Not estimableTotal events: 0 (IPC), 0 (No treatment)Test for heterogeneity: not applicableTest for overall effect: not applicable0.1 0.2 0.5 1 2 5 10Favours treatmentFavours controlAnalysis 12.03.Review:Comparison:Outcome:Comparison 12 Thromboembolic events (TE). IPC vs. no treatment, Outcome 03 DVT and/orPE. Same as in “DVT”.Heparins and mechanical methods for thromboprophylaxis in colorectal surgery12 Thromboembolic events (TE). IPC vs. no treatment03 DVT and/or PE. Same as in ”DVT”.Study IPC No treatment Peto Odds Ratio Weight Peto Odds Ration/N n/N 95% CI (%) 95% CITotal (95% CI) 0 0 0.0 Not estimableTotal events: 0 (IPC), 0 (No treatment)Test for heterogeneity: not applicableTest for overall effect: not applicable0.1 0.2 0.5 1 2 5 10Favours treatmentFavours controlHeparins and mechanical methods for thromboprophylaxis in colorectal surgery (Review)Copyright © 2006 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd37