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Meta-Analysis
. 2018 Jul 11;7(7):CD009447.
doi: 10.1002/14651858.CD009447.pub3.

Anticoagulation for perioperative thromboprophylaxis in people with cancer

Charbel F Matar  1 , Lara A Kahale, Maram B Hakoum, Ibrahim G Tsolakian, Itziar Etxeandia-Ikobaltzeta, Victor Ed Yosuico, Irene Terrenato, Francesca Sperati, Maddalena Barba, Holger Schünemann, Elie A Akl
Affiliations
Meta-Analysis

Anticoagulation for perioperative thromboprophylaxis in people with cancer

Charbel F Matar et al. Cochrane Database Syst Rev. .

Abstract

Background: The choice of the appropriate perioperative thromboprophylaxis for people with cancer depends on the relative benefits and harms of different anticoagulants.

Objectives: To systematically review the evidence for the relative efficacy and safety of anticoagulants for perioperative thromboprophylaxis in people with cancer.

Search methods: This update of the systematic review was based on the findings of a comprehensive literature search conducted on 14 June 2018 that included a major electronic search of Cochrane Central Register of Controlled Trials (CENTRAL, 2018, Issue 6), MEDLINE (Ovid), and Embase (Ovid); handsearching of conference proceedings; checking of references of included studies; searching for ongoing studies; and using the 'related citation' feature in PubMed.

Selection criteria: Randomized controlled trials (RCTs) that enrolled people with cancer undergoing a surgical intervention and assessed the effects of low-molecular weight heparin (LMWH) to unfractionated heparin (UFH) or to fondaparinux on mortality, deep venous thrombosis (DVT), pulmonary embolism (PE), bleeding outcomes, and thrombocytopenia.

Data collection and analysis: Using a standardized form, we extracted data in duplicate on study design, participants, interventions outcomes of interest, and risk of bias. Outcomes of interest included all-cause mortality, PE, symptomatic venous thromboembolism (VTE), asymptomatic DVT, major bleeding, minor bleeding, postphlebitic syndrome, health related quality of life, and thrombocytopenia. We assessed the certainty of evidence for each outcome using the GRADE approach (GRADE Handbook).

Main results: Of 7670 identified unique citations, we included 20 RCTs with 9771 randomized people with cancer receiving preoperative prophylactic anticoagulation. We identified seven reports for seven new RCTs for this update.The meta-analyses did not conclusively rule out either a beneficial or harmful effect of LMWH compared with UFH for the following outcomes: mortality (risk ratio (RR) 0.82, 95% confidence interval (CI) 0.63 to 1.07; risk difference (RD) 9 fewer per 1000, 95% CI 19 fewer to 4 more; moderate-certainty evidence), PE (RR 0.49, 95% CI 0.17 to 1.47; RD 3 fewer per 1000, 95% CI 5 fewer to 3 more; moderate-certainty evidence), symptomatic DVT (RR 0.67, 95% CI 0.27 to 1.69; RD 3 fewer per 1000, 95% CI 7 fewer to 7 more; moderate-certainty evidence), asymptomatic DVT (RR 0.86, 95% CI 0.71 to 1.05; RD 11 fewer per 1000, 95% CI 23 fewer to 4 more; low-certainty evidence), major bleeding (RR 1.01, 95% CI 0.69 to 1.48; RD 0 fewer per 1000, 95% CI 10 fewer to 15 more; moderate-certainty evidence), minor bleeding (RR 1.01, 95% CI 0.76 to 1.33; RD 1 more per 1000, 95% CI 34 fewer to 47 more; moderate-certainty evidence), reoperation for bleeding (RR 0.93, 95% CI 0.57 to 1.50; RD 4 fewer per 1000, 95% CI 22 fewer to 26 more; moderate-certainty evidence), intraoperative transfusion (mean difference (MD) -35.36 mL, 95% CI -253.19 to 182.47; low-certainty evidence), postoperative transfusion (MD 190.03 mL, 95% CI -23.65 to 403.72; low-certainty evidence), and thrombocytopenia (RR 3.07, 95% CI 0.32 to 29.33; RD 6 more per 1000, 95% CI 2 fewer to 82 more; moderate-certainty evidence). LMWH was associated with lower incidence of wound hematoma (RR 0.70, 95% CI 0.54 to 0.92; RD 26 fewer per 1000, 95% CI 39 fewer to 7 fewer; moderate-certainty evidence). The meta-analyses found the following additional results: outcomes intraoperative blood loss (MD -6.75 mL, 95% CI -85.49 to 71.99; moderate-certainty evidence); and postoperative drain volume (MD 30.18 mL, 95% CI -36.26 to 96.62; moderate-certainty evidence).In addition, the meta-analyses did not conclusively rule out either a beneficial or harmful effect of LMWH compared with Fondaparinux for the following outcomes: any VTE (DVT or PE, or both; RR 2.51, 95% CI 0.89 to 7.03; RD 57 more per 1000, 95% CI 4 fewer to 228 more; low-certainty evidence), major bleeding (RR 0.74, 95% CI 0.45 to 1.23; RD 8 fewer per 1000, 95% CI 16 fewer to 7 more; low-certainty evidence), minor bleeding (RR 0.83, 95% CI 0.34 to 2.05; RD 8fewer per 1000, 95% CI 33 fewer to 52 more; low-certainty evidence), thrombocytopenia (RR 0.35, 95% CI 0.04 to 3.30; RD 14 fewer per 1000, 95% CI 20 fewer to 48 more; low-certainty evidence), any PE (RR 3.13, 95% CI 0.13 to 74.64; RD 2 more per 1000, 95% CI 1 fewer to 78 more; low-certainty evidence) and postoperative drain volume (MD -20.00 mL, 95% CI -114.34 to 74.34; low-certainty evidence) AUTHORS' CONCLUSIONS: We found no difference between perioperative thromboprophylaxis with LMWH versus UFH and LMWH compared with fondaparinux in their effects on mortality, thromboembolic outcomes, major bleeding, or minor bleeding in people with cancer. There was a lower incidence of wound hematoma with LMWH compared to UFH.

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Conflict of interest statement

CFM: declares no conflicts of interests LAK: declares no conflicts of interests MBH: declares no conflicts of interests. IGT: declares no conflicts of interests. IEI: declares no conflicts of interests VY: declares no conflicts of interests. IT: declares no conflicts of interests FS: declares conflicts of interests MB: declares conflicts of interests HS: panel member of the ASH VTE in Cancer patients, Vice‐Chair of the ASH VTE guidelines and played various leadership roles from 1999 until 2014 with ACCP VTE guidelines. EAA served on the executive committee the ACCP Antithrombotic Therapy Guidelines published in 2016.

Figures

1
1
Study flow diagram. CVC: central venous catheter; LMWH: low‐molecular weight heparin; RCT: randomized controlled trial; UFH: unfractionated heparin; VTE: venous thromboembolism.
2
2
Risk of bias graph: review authors' judgments about each risk of bias item presented as percentages across all included studies.
3
3
Risk of bias summary: review authors' judgments about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1 Low‐molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 1 All‐cause mortality.
1.2
1.2. Analysis
Comparison 1 Low‐molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 2 Pulmonary embolism (PE).
1.3
1.3. Analysis
Comparison 1 Low‐molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 3 Symptomatic deep venous thrombosis (DVT).
1.4
1.4. Analysis
Comparison 1 Low‐molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 4 Asymptomatic DVT.
1.5
1.5. Analysis
Comparison 1 Low‐molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 5 Major bleeding.
1.6
1.6. Analysis
Comparison 1 Low‐molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 6 Minor bleeding.
1.7
1.7. Analysis
Comparison 1 Low‐molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 7 Wound hematoma.
1.8
1.8. Analysis
Comparison 1 Low‐molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 8 Reoperation for bleeding.
1.9
1.9. Analysis
Comparison 1 Low‐molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 9 Intraoperative transfusion.
1.10
1.10. Analysis
Comparison 1 Low‐molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 10 Postoperative transfusion.
1.11
1.11. Analysis
Comparison 1 Low‐molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 11 Intraoperative blood loss.
1.12
1.12. Analysis
Comparison 1 Low‐molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 12 Postoperative drain volume.
1.13
1.13. Analysis
Comparison 1 Low‐molecular weight heparin (LMWH) versus unfractionated heparin (UFH), Outcome 13 Thrombocytopenia.
2.1
2.1. Analysis
Comparison 2 Low molecular weight heparin (LMWH) versus Fondaparinux, Outcome 1 Any pulmonary embolism.
2.2
2.2. Analysis
Comparison 2 Low molecular weight heparin (LMWH) versus Fondaparinux, Outcome 2 Any venous thromboembolism (VTE).
2.3
2.3. Analysis
Comparison 2 Low molecular weight heparin (LMWH) versus Fondaparinux, Outcome 3 Major Bleeding.
2.4
2.4. Analysis
Comparison 2 Low molecular weight heparin (LMWH) versus Fondaparinux, Outcome 4 Minor Bleeding.
2.5
2.5. Analysis
Comparison 2 Low molecular weight heparin (LMWH) versus Fondaparinux, Outcome 5 Postoperative drain volume.
2.6
2.6. Analysis
Comparison 2 Low molecular weight heparin (LMWH) versus Fondaparinux, Outcome 6 Thrombocytopenia.
See this image and copyright information in PMC

Update of

References

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Agnelli 2015 (AMPLIFY) {published data only}
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Auer 2011a {published data only}
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Auer 2011b {published data only}
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Bergqvist 1988 {published data only}
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Bergqvist 2006 {published data only}
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Bigg 1992 {published data only}
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Boneu 1993 {published data only}
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Borstad 1988 {published data only}
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Cade 1983 {published data only}
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Caprini 2003 {published data only}
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Chodri 2002 {published data only}
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Ciftci 2012 {published data only}
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Clarke‐Pearson 1983 {published data only}
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Clarke‐Pearson 1984 {published data only}
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Clarke‐Pearson 1993 {published data only}
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Clark‐Pearson 1990a {published data only}
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Clark‐Pearson 1990b {published data only}
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Cohen 2006 {published data only}
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Cohen 2007 (PREVENT) {published data only}
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Couban 2005 {published data only}
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Dickinson 1998 {published data only}
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Dindelli 1990 {published data only}
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Di Somma 1992 {published data only}
    1. Somma C, Canepa G, Gipponi M, Frascio M. The postoperative prevention of deep venous thrombosis and pulmonary embolism with defibrotide versus heparin‐calcium: a randomized clinical multicenter study of 1296 patients undergoing major abdominal surgery. Annali Italiani di Chirurgia 1992;63(1):83‐8. - PubMed
Gondret 1995 {published data only}
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Haas 2011 {published data only}
    1. Bauersachs R, Schellong SM, Haas S, Tebbe U, Gerlach HE, Abletshauser, et al. CERTIFY: prophylaxis of venous thromboembolism in patients with severe renal insufficiency. Thrombosis and Haemostasis 2011;105(6):981‐8. - PubMed
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Harenberg 1996 {published data only}
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Ho 1999 {published data only}
    1. Ho YH, Seow‐Choen F, Leong A, Eu KW, Nyam D, Teoh MK. Randomized, controlled trial of low molecular weight heparin vs. no deep vein thrombosis prophylaxis for major colon and rectal surgery in Asian patients. Diseases of the Colon & Rectum 1999;42(2):196‐202. - PubMed
Jorgensen 2002 {published data only}
    1. Jorgensen LN, Lausen I, Rasmussen MS, Willie Jorgensen P, Bergqvist D. Prolonged thromboprophylaxis with low‐molecular weight heparin following major general surgery: an individual patient data meta‐analysis. Blood 2002;100:1952.
Kakkar 1985 {published data only}
    1. Kakkar VV, Murray WJ. Efficacy and safety of low‐molecular‐weight heparin (CY216) in preventing postoperative venous thrombo‐embolism: a co‐operative study. British Journal of Surgery 1985;72:786‐91. - PubMed
Kakkar 1989 {published data only}
    1. Kakkar VV, Stringer MD, Hedges AR, Parker CJ, Welzel D, Ward VP, et al. Fixed combinations of low‐molecular weight or unfractionated heparin plus dihydroergotamine in the prevention of postoperative deep vein thrombosis. American Journal of Surgery 1989;157:413‐8. - PubMed
Kakkar 2009 {published data only}
    1. Kakkar VV, Balibrea J, Martinez‐Gonzalez J, Prandoni P. Late breaking clinical trial: a randomised double blind trial to evaluate the efficacy and safety of prolonging the thromboprophylaxis with bemiparin in patients undergoing cancer abdominal or pelvic surgery (the CANBESURE study). International Society on Thrombosis and Haemostasis 2009;7(Suppl 2):1‐1204.
Kakkar 2010 (CANBESURE) {published data only}
    1. Kakkar VV, Balibrea J, Martinez‐Gonzalez J, Prandoni P. Late breaking clinical trial: a randomised double blind trial to evaluate the efficacy and safety of prolonging the thromboprophylaxis with bemiparin in patients undergoing cancer abdominal or pelvic surgery (the CANBESURE study). International Society on Thrombosis and Haemostasis 2009;7(Suppl 2):1202, LB‐MO‐002.
    1. Kakkar VV, Balibrea JL, Martinez‐Gonzalez J, Prandoni P. Extended prophylaxis with bemiparin for the prevention of venous thromboembolism after abdominal or pelvic surgery for cancer: the CANBESURE randomized study. Journal of Thrombosis and Haemostasis 2010;8(6):1223‐9. - PubMed
Kakkar 2010a {published data only}
    1. Kakkar VV, Balibrea JL, Martínez‐González J, Prandoni P, CANBESURE Study Group. Extended prophylaxis with bemiparin for the prevention of venous thromboembolism after abdominal or pelvic surgery for cancer: the CANBESURE randomized study. Journal of Thrombosis and Haemostasis 2010;8:1223‐9. - PubMed
Kakkar 2010b {published data only}
    1. Kakkar AK, Agnelli G, Fisher WD, George D, Mouret P, Lassen MR, et al. The ultra‐low‐molecular‐weight heparin semuloparin for prevention of venous thromboembolism in patients undergoing major abdominal surgery. Blood 2010;116:188.
Kakkar 2014 (SAVE‐ABDO) {published data only}
    1. Kakkar AK, Agnelli G, Fisher W, George D, Lassen MR, Mismetti P, et al. SAVE‐ABDO Investigators. Preoperative enoxaparin versus postoperative semuloparin thromboprophylaxis in major abdominal surgery: a randomized controlled trial. Annals of Surgery 2014;259(6):1073‐9. - PubMed
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Khorana 2017 (PHACS) {published data only}
    1. Khorana AA, Francis CW, Kuderer N, Carrier M, Ortel TL, Wun T, et al. Dalteparin thromboprophylaxis in cancer patients at high risk for venous thromboembolism: a randomized trial. Blood 2015;126(23):427. - PubMed
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Larocca 2012 {published data only}
    1. Larocca A, Cavallo F, Bringhen S, Raimondo FD, Falanga A, Evangelista A, et al. Aspirin or enoxaparin thromboprophylaxis for patients with newly diagnosed multiple myeloma treated with lenalidomide. Blood 2012;119:933‐9. - PubMed
Lausen 1998 {published data only}
    1. Lausen I, Jensen R, Jorgensen LN, Rasmussen MS, Lyng KM, Andersen M, et al. Incidence and prevention of deep venous thrombosis occurring late after general surgery: randomised controlled study of prolonged thromboprophylaxis. European Journal of Surgery 1998;164:657‐63. - PubMed
Lee 2015 (CATCH) {published data only}
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Liezorovicz 1991 {published data only}
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    1. Limmer J, Ellbruck D, Muller H, Eisele E, Rist J, Schutze F, et al. Prospective randomized clinical study in general surgery comparing a new low molecular weight heparin with unfractionated heparin in the prevention of thrombosis. Clinical Investigator 1994;72:913‐9. - PubMed
Macbeth 2016 (FRAGMATIC) {published data only}
    1. Griffiths GO, Burns S, Noble SI, Macbeth FR, Cohen D, Maughan TS. FRAGMATIC: a randomised phase III clinical trial investigating the effect of Fragmin® added to standard therapy in patients with lung cancer. BMC Cancer 2009;9(1):1. - PMC - PubMed
    1. Macbeth F, Noble S, Evans J, Ahmed S, Cohen D, Hood K, et al. Randomized phase III trial of standard therapy plus low molecular weight heparin in patients with lung cancer: FRAGMATIC trial. Journal of Clinical Oncology 2016;34(5):488‐94. - PubMed
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    1. Noble S, Robbins A, Alikhan R, Hood K, Macbeth F. Prediction of venous thromboembolism in lung cancer patients receiving chemotherapy. Journal of Thrombosis and Haemostasis 2015;13:143.
Macdonald 2003 {published data only}
    1. Macdonald RL, Amidei C, Baron J, Weir B, Brown F, Erickson RK, et al. Randomized, pilot study of intermittent pneumatic compression devices plus dalteparin versus intermittent pneumatic compression devices plus heparin for prevention of venous thromboembolism in patients undergoing craniotomy. Surgical Neurology 2003;59:363. - PubMed
Marassi 1993 {published data only}
    1. Marassi A, Balzano G, Mari G, D'Angelo SV, Della Valle P, Carlo V, et al. Prevention of postoperative deep vein thrombosis in cancer patients. A randomized trial with low molecular weight heparin (CY 216). International Surgery 1993;78(2):166‐70. - PubMed
Maxwell 2001 {published data only}
    1. Maxwell GL, Synan I, Dodge R, Carroll B, Clarke‐Pearson DL. Pneumatic compression versus low molecular weight heparin in gynecologic oncology surgery: a randomized trial. American College of Obstetricians and Gynecologists 2001;98(6):989‐95. - PubMed
Mazilu 2014 (OVIDIUS) {published data only}
    1. Mazilu L, Parepa IR, Suceveanu AI, Suceveanu A, Baz R, Catrinoiu D. Venous thromboembolism: secondary prevention with dabigatran vs. acenocumarol in patients with paraneoplastic deep vein thrombosis. Results from a small prospective study in Romania. Cardiovascular Research 2014;103(Suppl 1):S39, P221.
Murakami 2002 {published data only}
    1. Cahan MA, Hanna DJ, Wiley LA, Cox DK, Killewich LA. External pneumatic compression and fibrinolysis in abdominal surgery. Journal of Vascular Surgery 2000;32(3):537‐43. - PubMed
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Nagata 2015 {published data only}
    1. Nagata C, Tanabe H, Takakura S, Narui C, Saito M, Yanaihara N, et al. Randomized controlled trial of enoxaparin versus intermittent pneumatic compression for venous thromboembolism prevention in Japanese surgical patients with gynecologic malignancy. Journal of Obstetrics and Gynaecology Research 2015;41(9):1440‐8. - PubMed
Nurmohamed 1995 {published data only}
    1. Nurmohamed MT, Verhaeghe R, Haas S, Iriarte JA, Vogel G, Rij AM, et al. A comparative trial of a low molecular weight heparin (enoxaparin) versus standard heparin for the prophylaxis of postoperative deep vein thrombosis in general surgery. American Journal of Surgery 1995;169(6):567‐71. - PubMed
Nurmohamed 1996 {published data only}
    1. Nurmohamed MT, Riel AM, Henkens CM, Koopman, Que GT, d'Azemar P, et al. Low molecular weight heparin and compression stockings in the prevention of venous thromboembolism in neurosurgery. Thrombosis Haemostasis 1996;75:233‐8. - PubMed
Palumbo 2011 {published data only}
    1. Cavo M, Palumbo A, Bringhen S, Raimondo F, Patriarca F, Rossi D, et al. Phase III study of enoxaparin versus aspirin versus low‐dose warfarin as thromboprophylaxis for patients with newly diagnosed multiple myeloma treated upfront with thalidomide‐containing regimens. Haematologica 2010;95:391.
    1. Cavo M, Palumbo A, Bringhen S, Falcone A, Musto P, Ciceri F, et al. A phase III study of enoxaparin versus low‐dose warfarin versus aspirin as thromboprophylaxis for patients with newly diagnosed multiple myeloma treated up‐front with thalidomide‐containing regimens. Blood 2008;112(11):3017.
    1. Cavo M, Palumbo A, Bringhen S, Falcone A, Musto P, Ciceri F, et al. A phase III study of enoxaparin versus low‐dose warfarin versus aspirin as thromboprophylaxis for patients with newly diagnosed multiple myeloma treated up‐front with thalidomide‐containing regimens. Haematologica 2009;94:s4.
    1. Magarotto V, Brioli A, Patriarca F, Rossi D, Petrucci MT, Nozzoli C, et al. Enoxaparin, aspirin, or warfarin for the thromboprophylaxis in newly diagnosed myeloma patients receiving thalidomide: a randomized controlled trial. XI Congress of the Italian Society of Experimental Hematology 2010;95:986‐993.
    1. Palumbo A, Cavo M, Bringhen S, Zaccaria A, Spadano A, Palmieri S, et al. Enoxaparin versus aspirin versus low‐fixed‐dose of warfarin in newly diagnosed myeloma patients treated with thalidomide‐containing regimens: a randomized, controlled trial. Haematologica 2008;93:362.
Pelzer 2015 (CONKO‐004) {published data only}
    1. Pelzer U, Deutschinoff G, Opitz B, Stauch M, Reitzig P, Hahnfeld S, et al. A prospective, randomized trial of simultaneous pancreatic cancer treatment with enoxaparin and chemotherapy ‐ first results of the CONKO 004 trial. Onkologie ‐ DGHO meeting October 2009; Vol. 580:Abstract.
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    1. Pelzer U, Hilbig A, Stieler JM, Bahra M, Sinn M, Gebauer B, et al. Intensified chemotherapy and simultaneous treatment with heparin in outpatients with pancreatic cancer ‐ the CONKO 004 pilot trial. BMC Cancer 2014;14:204. - PMC - PubMed
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Prins 2014 (EINSTEIN) {published data only}
    1. Prins MH, Lensing AW, Brighton TA, Lyons RM, Rehm J, Trajanovic M, et al. Oral rivaroxaban versus enoxaparin with vitamin K antagonist for the treatment of symptomatic venous thromboembolism in patients with cancer (EINSTEIN‐DVT and EINSTEIN‐PE): a pooled subgroup analysis of two randomised controlled trials. Lancet Haematology 2014;1(1):e37‐46. - PubMed
Raskob 2016 (HOKUSAI) {published data only}
    1. Raskob GE, Es N, Segers A, Angchaisuksiri P, Oh D, Boda Z, et al. Edoxaban for venous thromboembolism in patients with cancer: results from a non‐inferiority subgroup analysis of the Hokusai‐VTE randomised, double‐blind, double‐dummy trial. Lancet Haematology 2016;3(8):e379‐87. - PubMed
Raskob 2018 (HOKUSAI) {published data only}
    1. Raskob GE, Es N, Verhamme P, Carrier M, Nisio M, Garcia DA, et al. A randomized, open‐label, blinded outcome assessment trial evaluating the efficacy and safety of LMWH/edoxaban versus dalteparin for venous thromboembolism associated with cancer: Hokusai VTE‐Cancer study (LBA‐6). Blood 2017;130:LBA‐6.
    1. Raskob GE, Es N, Verhamme P, Carrier M, Nisio M, Garcia D, et al. Edoxaban for the treatment of cancer‐associated venous thromboembolism. New England Journal of Medicine 2018;378(7):615‐24. - PubMed
Rasmussen 2006 {published data only}
    1. Rasmussen M, Wille‐Jorgensen P, Jorgensen LN, Nielsen JD, Horn A, et al. Prolonged thromboprophylaxis with low molecular weight heparin (dalteparin) following major abdominal surgery for malignancy. Blood 2003;102:186.
    1. Rasmussen MS, Jorgensen L, Wille‐Jorgensen P, Nielsen J, Soemod L, Harvald T, et al. Prolonged thromboprophylaxis with dalteparin after major abdominal surgery for malignant diseases. ASCO Proceedings 2001;4:407a.
    1. Rasmussen MS, Jorgensen LN, Wille‐Jorgensen P, Nielsen JD, Horn A, Mohn AC, et al. Prolonged prophylaxis with dalteparin to prevent late thromboembolic complications in patients undergoing major abdominal surgery: a multicenter randomized open‐label study. Journal of Thrombosis and Haemostasis 2006;4:2384‐90. - PubMed
Sakon 2010 {published data only}
    1. Sakon M, Kobayashi T, Shimazui T. Efficacy and safety of enoxaparin in Japanese patients undergoing curative abdominal or pelvic cancer surgery: results from a multicenter, randomized, open‐label study. Thrombosis Research 2010;125(3):e65‐70. - PubMed
Samama 1988 {published data only}
    1. Samama M, Bernard P, Bonnardot JP, Combe‐Tamzali S, Lanson Y, Tissot E. Low molecular weight heparin compared with unfractionated heparin in prevention of postoperative thrombosis. British Journal of Surgery 1988;75:128‐31. - PubMed
Schulman 2003 {published data only}
    1. Schulman S, Wahlander K, Lundstrom T, Clason SB, Eriksson H, Investigators TI, et al. Secondary prevention of venous thromboembolism with the oral direct thrombin inhibitor ximelagatran. New England Journal of Medicine 2003;349(18):1713‐21. - PubMed
Schulman 2013 (RE‐MEDY) {published data only}
    1. Schulman S, Kearon C, Kakkar AK, Schellong S, Eriksson H, Baanstra D, et al. Extended use of dabigatran, warfarin, or placebo in venous thromboembolism. New England Journal of Medicine 2013;368(8):709‐18. - PubMed
Schulman 2015 (RECOVER) {published data only}
    1. Schulman S, Goldhaber SZ, Kearon C, Kakkar AK, Schellong S, Eriksson H, et al. Treatment with dabigatran or warfarin in patients with venous thromboembolism and cancer. Thrombosis and Haemostasis 2015;114(1):150‐7. - PubMed
Shukla 2008 {published data only}
    1. Shukla PJ, Siddachari R, Ahire S, Arya S, Ramani S, Barreto SG, et al. Postoperative deep vein thrombosis in patients with colorectal cancer. Indian Journal of Gastroenterology 2008;27(2):71‐3. - PubMed
Simonneau 2006 {published data only}
    1. Simonneau G, Laporte S, Mismetti P, Derlon A, Samii K, Samama CM, et al. A randomized study comparing the efficacy and safety of nadroparin 2850 IU (0.3 mL) vs. enoxaparin 4000 IU (40mg) in the prevention of venous thromboembolism after colorectal surgery for cancer. Journal of Thrombosis and Haemostasis 2006;4:1693‐700. - PubMed
Song 2014 {published data only}
    1. Song KY, Yoo HM, Kim EY, Kim JI, Yim HW, Jeon HM, et al. Optimal prophylactic method of venous thromboembolism for gastrectomy in Korean patients: an interim analysis of prospective randomized trial. Annals of Surgical Oncology 2014;21(13):4232‐8. - PubMed
Tang 2012 {published data only}
    1. Tang BQ, Guo W, Yang RL, Tang XD, Yan TQ, Tang S. Evaluation of efficacy and safety of rivaroxaban in the prevention of postoperative venous thromboembolism in adult patients with primary bone tumor undergoing knee operation. Zhonghua Yi Xue za Zhi 2012;92(39):2768‐771. - PubMed
Vadhan‐Raj 2013 {published data only}
    1. Vadhan‐Raj S, Zhou X, Varadhachary GR, Milind J, Fogelman D, Shroff R, et al. Randomized controlled trial of dalteparin for primary thromboprophylaxis for venous thromboembolism (VTE) in patients with advanced pancreatic cancer (APC): risk factors predictive of VTE. Blood 2013;122(21):580.
Vedovati 2014a {published data only}
    1. Becattini C, Rondelli F, Vedovati MC, Camporese G, Giustozzi M, Boncompagni M, et al. Incidence and risk factors for venous thromboembolism after laparoscopic surgery for colorectal cancer. Haematologia 2014;100(1):e35‐8. - PMC - PubMed
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    1. Vedovati MC, Becattini C, Rondelli F, Boncompagni M, Camporese G, Balzarotti R, et al. A randomized study on 1‐week versus 4‐week prophylaxis for venous thromboembolism after laparoscopic surgery for colorectal cancer. Annals of Surgery 2014;259(4):665‐9. - PubMed
Vedovati 2014b {published data only}
    1. Becattini C, Rondelli F, Vedovati MC, Camporese G, Giustozzi M, Boncompagni M, et al. Incidence and risk factors for venous thromboembolism after laparoscopic surgery for colorectal cancer. Haematologica 2015;100(1):e35‐8. - PMC - PubMed
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    1. Vedovati MC, Becattini C, Rondelli F, Boncompagni M, Camporese G, Balzarotti R, et al. A randomized study on 1 vs. 4 weeks prophylaxis for venous thromboembolism after laparoscopic surgery for colorectal cancer. Journal of Thrombosis and Haemostasis 2013;11:214.
    1. Vedovati MC, Becattini C, Rondelli F, Boncompagni M, Camporese G, Balzarotti R, et al. A randomized study on 1‐week versus 4‐week prophylaxis for venous thromboembolism after laparoscopic surgery for colorectal cancer. Annals of Surgery 2014;259(4):665‐9. - PubMed
Verso 2008 {published data only}
    1. Agnelli G, Verso M, Bertoglio S, Ageno W, Bazzan M, Parise P, et al. A double‐blind placebo‐controlled randomized study on the efficacy and safety of enoxaparin for the prevention of upper limb deep vein thrombosis in cancer patients with central vein catheter. Journal of Clinical Oncology 2004;22:734S. - PubMed
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Young 2017 (SELECT‐D) {published data only}
    1. Young A, Dunn J, Chapman O, Grumett J, Marshall A, Phillips J, et al. SELECT‐D: anticoagulation therapy in selected cancer patients at risk of recurrence of venous thromboembolism. ASCO Annual Meeting Proceedings 2014;32(15 Suppl):TPS9661. - PubMed
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    1. Young A, Phillips J, Hancocks H, Hill C, Joshi N, Marshall A, et al. OC‐11‐Anticoagulation therapy in selected cancer patients at risk of recurrence of venous thromboembolism. Thrombosis Research 2016;140:S172‐3. - PubMed
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Zheng 2014 {published data only}
    1. Zheng H, Gao Y, Yan X, Gao M, Gao W. Prophylactic use of low molecular weight heparin in combination with graduated compression stockings in post‐operative patients with gynecologic cancer. Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology] 2014;36(1):39‐42. - PubMed
Zwicker 2013 (MICRO TEC) {published data only}
    1. Zwicker J, Liebman HA, Bauer KA, Caughey T, Rosovsky R, Mantha S, et al. A randomized‐controlled phase II trial of primary thromboprophylaxis with enoxaparin in cancer patients with elevated tissue factor bearing microparticles (the MICROTEC study). Journal of Thrombosis and Haemostasis : JTH 2013;11:6. - PMC - PubMed
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References to ongoing studies

Safi 2011 {published data only}
    1. A Randomized, Controlled, Open Label Study of the Efficacy and Safety of the Low Molecular Weight Heparin (LMWH), LovenoxTM (Enoxaparin) versus HeparinTM (Unfractionated Heparin) for Prevention of Venous Thromboembolism (VTE) in Gynecologic Oncology Patients. Ongoing study October 2009.

Additional references

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References to other published versions of this review

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