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. 2019 Dec;23(63):1–190. doi: 10.3310/hta23630

Different strategies for pharmacological thromboprophylaxis for lower-limb immobilisation after injury: systematic review and economic evaluation.

Abdullah Pandor, Daniel Horner, Sarah Davis, Steve Goodacre, John W Stevens, Mark Clowes, Beverley J Hunt, Tim Nokes, Jonathan Keenan, Kerstin de Wit
PMCID: PMC6936165  PMID: 31851608

Abstract

BACKGROUND

Thromboprophylaxis can reduce the risk of venous thromboembolism (VTE) during lower-limb immobilisation, but it is unclear whether or not this translates into meaningful health benefit, justifies the risk of bleeding or is cost-effective. Risk assessment models (RAMs) could select higher-risk individuals for thromboprophylaxis.

OBJECTIVES

To determine the clinical effectiveness and cost-effectiveness of different strategies for providing thromboprophylaxis to people with lower-limb immobilisation caused by injury and to identify priorities for future research.

DATA SOURCES

Ten electronic databases and research registers (MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Database of Abstracts of Review of Effects, the Cochrane Central Register of Controlled Trials, Health Technology Assessment database, NHS Economic Evaluation Database, Science Citation Index Expanded, ClinicalTrials.gov and the International Clinical Trials Registry Platform) were searched from inception to May 2017, and this was supplemented by hand-searching reference lists and contacting experts in the field.

REVIEW METHODS

Systematic reviews were undertaken to determine the effectiveness of pharmacological thromboprophylaxis in lower-limb immobilisation and to identify any study of risk factors or RAMs for VTE in lower-limb immobilisation. Study quality was assessed using appropriate tools. A network meta-analysis was undertaken for each outcome in the effectiveness review and the results of risk-prediction studies were presented descriptively. A modified Delphi survey was undertaken to identify risk predictors supported by expert consensus. Decision-analytic modelling was used to estimate the incremental cost per quality-adjusted life-year (QALY) gained of different thromboprophylaxis strategies from the perspectives of the NHS and Personal Social Services.

RESULTS

Data from 6857 participants across 13 trials were included in the meta-analysis. Thromboprophylaxis with low-molecular-weight heparin reduced the risk of any VTE [odds ratio (OR) 0.52, 95% credible interval (CrI) 0.37 to 0.71], clinically detected deep-vein thrombosis (DVT) (OR 0.40, 95% CrI 0.12 to 0.99) and pulmonary embolism (PE) (OR 0.17, 95% CrI 0.01 to 0.88). Thromboprophylaxis with fondaparinux (Arixtra®, Aspen Pharma Trading Ltd, Dublin, Ireland) reduced the risk of any VTE (OR 0.13, 95% CrI 0.05 to 0.30) and clinically detected DVT (OR 0.10, 95% CrI 0.01 to 0.94), but the effect on PE was inconclusive (OR 0.47, 95% CrI 0.01 to 9.54). Estimates of the risk of major bleeding with thromboprophylaxis were inconclusive owing to the small numbers of events. Fifteen studies of risk factors were identified, but only age (ORs 1.05 to 3.48), and injury type were consistently associated with VTE. Six studies of RAMs were identified, but only two reported prognostic accuracy data for VTE, based on small numbers of patients. Expert consensus was achieved for 13 risk predictors in lower-limb immobilisation due to injury. Modelling showed that thromboprophylaxis for all is effective (0.015 QALY gain, 95% CrI 0.004 to 0.029 QALYs) with a cost-effectiveness of £13,524 per QALY, compared with thromboprophylaxis for none. If risk-based strategies are included, it is potentially more cost-effective to limit thromboprophylaxis to patients with a Leiden thrombosis risk in plaster (cast) [L-TRiP(cast)] score of ≥ 9 (£20,000 per QALY threshold) or ≥ 8 (£30,000 per QALY threshold). An optimal threshold on the L-TRiP(cast) receiver operating characteristic curve would have sensitivity of 84-89% and specificity of 46-55%.

LIMITATIONS

Estimates of RAM prognostic accuracy are based on weak evidence. People at risk of bleeding were excluded from trials and, by implication, from modelling.

CONCLUSIONS

Thromboprophylaxis for lower-limb immobilisation due to injury is clinically effective and cost-effective compared with no thromboprophylaxis. Risk-based thromboprophylaxis is potentially optimal but the prognostic accuracy of existing RAMs is uncertain.

FUTURE WORK

Research is required to determine whether or not an appropriate RAM can accurately select higher-risk patients for thromboprophylaxis.

STUDY REGISTRATION

This study is registered as PROSPERO CRD42017058688.

FUNDING

The National Institute for Health Research Health Technology Assessment programme.

Plain language summary

People who have their leg immobilised in a plaster cast or brace following an injury are at risk of developing a blood clot. Sometimes the clot can break up and lodge in the lungs, which can make the person seriously ill. Drugs that thin the blood (anticoagulants) can reduce the risk of blood clots, but they carry a small risk of serious bleeding. This study analysed all published trials of anticoagulants for people with leg immobilisation and found that, without treatment, there was a 1–2% risk of a serious blood clot. This risk was roughly halved by using anticoagulant treatment. These estimates were used in a simulation model of patient treatment and it was found that the benefit of anticoagulants in reducing blood clots (in terms of length and quality of life) outweighed the risks of bleeding. Next, all published studies of risk assessment tools were analysed. Risk assessment tools can be used to predict who is most likely to get a blood clot. There were only a few studies and they had significant weaknesses. The risk assessment tools in the simulation model were evaluated and it was found that the most cost-effective approach was to use a risk assessment tool to select approximately half of the patients for treatment (those at higher risk), while not treating those at lower risk. Treating only the higher-risk patients would be a cost-effective use of NHS resources, compared with treating nobody. Treating everybody, compared with just treating higher-risk patients, would improve outcomes for some patients but would not be a cost-effective use of NHS resources. This study suggests that anticoagulant drugs are an effective and potentially cost-effective way of preventing blood clots in people with leg immobilisation due to injury. Research is needed to determine whether or not risk assessment tools can accurately predict who needs anticoagulant drugs and who does not.

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References

  1. National Institute for Health and Care Excellence. Venous Thromboembolism in Over 16s – Reducing the Risk of Hospital-acquired Deep Vein Thrombosis or Pulmonary Embolism. [NG89]. London: NICE; 2018. URL: www.nice.org.uk/guidance/ng89 (accessed 9 April 2018). [PubMed]
  2. Goldhaber SZ, Visani L, De Rosa M. Acute pulmonary embolism: clinical outcomes in the International Cooperative Pulmonary Embolism Registry (ICOPER). Lancet 1999;353:1386–9. https://doi.org/10.1016/S0140-6736(98)07534-5 doi: 10.1016/S0140-6736(98)07534-5. [DOI] [PubMed]
  3. Prandoni P, Lensing AW, Cogo A, Cuppini S, Villalta S, Carta M, et al. The long-term clinical course of acute deep venous thrombosis. Ann Intern Med 1996;125:1–7. https://doi.org/10.7326/0003-4819-125-1-199607010-00001 doi: 10.7326/0003-4819-125-1-199607010-00001. [DOI] [PubMed]
  4. Cohen AT, Agnelli G, Anderson FA, Arcelus JI, Bergqvist D, Brecht JG, et al. Venous thromboembolism (VTE) in Europe. The number of VTE events and associated morbidity and mortality. Thromb Haemost 2007;98:756–64. https://doi.org/10.1160/TH07-03-0212 doi: 10.1160/TH07-03-0212. [DOI] [PubMed]
  5. Raskob GE, Angchaisuksiri P, Blanco AN, Buller H, Gallus A, Hunt BJ, et al. Thrombosis: a major contributor to global disease burden. Arterioscler Thromb Vasc Biol 2014;34:2363–71. https://doi.org/10.1161/ATVBAHA.114.304488 doi: 10.1161/ATVBAHA.114.304488. [DOI] [PubMed]
  6. House of Commons Health Committee. The Prevention of Venous Thromboembolism in Hospitalised Patients – Second Report of Session 2004–05. London: The Stationery Office; 2005. URL: www.publications.parliament.uk/pa/cm200405/cmselect/cmhealth/99/99.pdf (accessed 15 March 2018).
  7. Chen L, Soares D. Fatal pulmonary embolism following ankle fracture in a 17-year-old girl. J Bone Joint Surg Br 2006;88:400–1. https://doi.org/10.1302/0301-620X.88B3.17152 doi: 10.1302/0301-620X.88B3.17152. [DOI] [PubMed]
  8. Healy B, Levin E, Perrin K, Weatherall M, Beasley R. Prolonged work- and computer-related seated immobility and risk of venous thromboembolism. J R Soc Med 2010;103:447–54. https://doi.org/10.1258/jrsm.2010.100155 doi: 10.1258/jrsm.2010.100155. [DOI] [PMC free article] [PubMed]
  9. Makhdom AM, Cota A, Saran N, Chaytor R. Incidence of symptomatic deep venous thrombosis after Achilles tendon rupture. J Foot Ankle Surg 2013;52:584–7. https://doi.org/10.1053/j.jfas.2013.03.001 doi: 10.1053/j.jfas.2013.03.001. [DOI] [PubMed]
  10. Makhdom AM, Garceau S, Dimentberg R. Fatal pulmonary embolism following Achilles tendon repair: a case report and a review of the literature. Case Rep Orthop 2013;2013:401968. https://doi.org/10.1155/2013/401968 doi: 10.1155/2013/401968. [DOI] [PMC free article] [PubMed]
  11. Meek R, Tong RL. Venous thromboembolism in emergency department patients with rigid immobilization for lower leg injury: incidence and risk factors. Emerg Med Australas 2012;24:277–84. https://doi.org/10.1111/j.1742-6723.2012.01539.x doi: 10.1111/j.1742-6723.2012.01539.x. [DOI] [PubMed]
  12. Nilsson-Helander K, Thurin A, Karlsson J, Eriksson BI. High incidence of deep venous thrombosis after Achilles tendon rupture: a prospective study. Knee Surg Sports Traumatol Arthrosc 2009;17:1234–8. https://doi.org/10.1007/s00167-009-0727-y doi: 10.1007/s00167-009-0727-y. [DOI] [PubMed]
  13. Nokes TJ, Keenan J. Thromboprophylaxis in patients with lower limb immobilisation – review of current status. Br J Haematol 2009;146:361–8. https://doi.org/10.1111/j.1365-2141.2009.07737.x doi: 10.1111/j.1365-2141.2009.07737.x. [DOI] [PubMed]
  14. Patil S, Gandhi J, Curzon I, Hui AC. Incidence of deep-vein thrombosis in patients with fractures of the ankle treated in a plaster cast. J Bone Joint Surg Br 2007;89:1340–3. https://doi.org/10.1302/0301-620X.89B10.19241 doi: 10.1302/0301-620X.89B10.19241. [DOI] [PubMed]
  15. Testroote M, Stigter WA, Janssen L, Janzing HM. Low molecular weight heparin for prevention of venous thromboembolism in patients with lower-leg immobilization. Cochrane Database Syst Rev 2014;4:CD006681. https://doi.org/10.1002/14651858.CD006681.pub3 doi: 10.1002/14651858.CD006681.pub3. [DOI] [PubMed]
  16. Horner D, Bennett P, Ryan A, Gillet A. Thromboprophylaxis for ambulatory patients with immobilised lower limb trauma: a closed audit loop. Emerg Med J 2015;32:999. https://doi.org/10.1136/emermed-2015-205372.46 doi: 10.1136/emermed-2015-205372.46. [DOI]
  17. Roberts C, Horner D, Coleman G, Maitland L, Curl-Roper T, Smith R, et al. Guidelines in Emergency Medicine Network (GEMNet): guideline for the use of thromboprophylaxis in ambulatory trauma patients requiring temporary limb immobilisation. Emerg Med J 2013;30:968–82. https://doi.org/10.1136/emermed-2013-203134 doi: 10.1136/emermed-2013-203134. [DOI] [PubMed]
  18. Zee AA, van Lieshout K, van der Heide M, Janssen L, Janzing HM. Low molecular weight heparin for prevention of venous thromboembolism in patients with lower-limb immobilization. Cochrane Database Syst Rev 2017;8:CD006681. https://doi.org/10.1002/14651858.CD006681.pub4 doi: 10.1002/14651858.CD006681.pub4. [DOI] [PMC free article] [PubMed]
  19. Smith R, Wood E. BET 4: quantifying the risk of venous thromboembolism for temporary lower limb immobilisation in ambulatory patients. Emerg Med J 2012;29:779–80. https://doi.org/10.1136/emermed-2012-201686.5 doi: 10.1136/emermed-2012-201686.5. [DOI] [PubMed]
  20. Hill AB, Garber B, Dervin G, Howard A. Heparin prophylaxis for deep vein thrombosis in a patient with multiple injuries: an evidence-based approach to a clinical problem. Can J Surg 2002;45:282–587. [PMC free article] [PubMed]
  21. Joint Formulary Committee. British National Formulary (online). London: BMJ Group and Pharmaceutical Press. URL: www.medicinescomplete.com (accessed 24 January 2018).
  22. Braithwaite I, Dunbar L, Eathorne A, Weatherall M, Beasley R. Venous thromboembolism rates in patients with lower limb immobilization after Achilles tendon injury are unchanged after the introduction of prophylactic aspirin: audit. J Thromb Haemost 2016;14:331–5. https://doi.org/10.1111/jth.13224 doi: 10.1111/jth.13224. [DOI] [PubMed]
  23. Gehling H, Giannadakis K, Lefering R, Hessmann M, Achenbach S, Gotzen L. [Prospective randomized pilot study of ambulatory prevention of thromboembolism. 2 times 500 mg aspirin (ASS) vs. clivarin 1750 (NMH).] Unfallchirurg 1998;101:42–9. https://doi.org/10.1007/s001130050231 doi: 10.1007/s001130050231. [DOI] [PubMed]
  24. National Clinical Guideline Centre – Acute and Chronic Conditions (UK). Venous Thromboembolism: Reducing the Risk of Venous Thromboembolism (Deep Vein Thrombosis and Pulmonary Embolism) in Patients Admitted to Hospital. [CG92]. London: Royal College of Physicians; 2010. URL: www.ncbi.nlm.nih.gov/books/NBK116518/ (accessed 4 March 2018). [PubMed]
  25. Electronic Medicines Compendium (eMC). Aspirin 75 mg Tablets – Summary of Product Characteristics (SmPC). Leatherhead: Datapharm. URL: www.medicines.org.uk/emc/product/2408 (accessed 12 March 2018).
  26. Electronic Medicines Compendium (eMC). Aspirin Tablets BP 300 mg – Patient Leaflet. Leatherhead: Datapharm. URL: www.medicines.org.uk/emc/product/8006 (accessed 12 March 2018).
  27. Lassen MR, Gallus A, Raskob GE, Pineo G, Chen D, Ramirez LM, ADVANCE-3 Investigators. Apixaban versus enoxaparin for thromboprophylaxis after hip replacement. N Engl J Med 2010;363:2487–98. https://doi.org/10.1056/NEJMoa1006885 doi: 10.1056/NEJMoa1006885. [DOI] [PubMed]
  28. Lassen MR, Raskob GE, Gallus A, Pineo G, Chen D, Hornick P, ADVANCE-2 investigators. Apixaban versus enoxaparin for thromboprophylaxis after knee replacement (ADVANCE-2): a randomised double-blind trial. Lancet 2010;375:807–15. https://doi.org/10.1016/S0140-6736(09)62125-5 doi: 10.1016/S0140-6736(09)62125-5. [DOI] [PubMed]
  29. Raskob GE, Gallus AS, Pineo GF, Chen D, Ramirez LM, Wright RT, Lassen MR. Apixaban versus enoxaparin for thromboprophylaxis after hip or knee replacement: pooled analysis of major venous thromboembolism and bleeding in 8464 patients from the ADVANCE-2 and ADVANCE-3 trials. J Bone Joint Surg Br 2012;94:257–64. https://doi.org/10.1302/0301-620X.94B2.27850 doi: 10.1302/0301-620X.94B2.27850. [DOI] [PubMed]
  30. Klarenbach S, Lee K, Boucher M, So H, Manns B, Tonelli M. Direct Oral Anticoagulants for the Treatment of Venous Thromboembolic Events: Economic Evaluation. Ottawa, ON: Canadian Agency for Drugs and Technologies in Health; 2016. URL: www.ncbi.nlm.nih.gov/books/NBK356126/ (accessed 19 March 2018). [PubMed]
  31. Keenan J, Hall M, Nokes T. A practical VTE risk assessment score tool for patients treated with lower limb cast immobilization. Injury Extra 2009;40:199–200. https://doi.org/10.1016/j.injury.2009.06.211 doi: 10.1016/j.injury.2009.06.211. [DOI]
  32. Nemeth B, van Adrichem RA, van Hylckama Vlieg A, Bucciarelli P, Martinelli I, Baglin T, et al. Venous thrombosis risk after cast immobilization of the lower extremity: derivation and validation of a clinical prediction score, L-TRiP(cast), in three population-based case-control studies. PLOS Med 2015;12:e1001899. https://doi.org/10.1371/journal.pmed.1001899 doi: 10.1371/journal.pmed.1001899. [DOI] [PMC free article] [PubMed]
  33. Stockport NHS Foundation Trust. Lower Limb Immobilisation VTE Risk Assessment Tool and Treatment Protocol. Stockport: Stockport NHS Foundation Trust; 2013. URL: www.boa.ac.uk/wp-content/uploads/2014/01/Stockport-VTE-Lower-limb-immobilisation.pdf (accessed 9 January 2018).
  34. Falck-Ytter Y, Francis CW, Johanson NA, Curley C, Dahl OE, Schulman S, et al. Prevention of VTE in orthopedic surgery patients: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141(Suppl. 2):e278–325. doi: 10.1378/chest.11-2404. [DOI] [PMC free article] [PubMed]
  35. Struijk-Mulder MC, Ettema HB, Verheyen CC, Büller HR. Comparing consensus guidelines on thromboprophylaxis in orthopedic surgery. J Thromb Haemost 2010;8:678–83. https://doi.org/10.1111/j.1538-7836.2009.03728.x doi: 10.1111/j.1538-7836.2009.03728.x. [DOI] [PubMed]
  36. Ettema HB, Kollen BJ, Verheyen CC, Büller HR. Prevention of venous thromboembolism in patients with immobilization of the lower extremities: a meta-analysis of randomized controlled trials. J Thromb Haemost 2008;6:1093–8. https://doi.org/10.1111/j.1538-7836.2008.02984.x doi: 10.1111/j.1538-7836.2008.02984.x. [DOI] [PubMed]
  37. Moher D, Liberati A, Tetzlaff J, Altman DG, PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLOS Med 2009;6:e1000097. https://doi.org/10.1371/journal.pmed.1000097 doi: 10.1371/journal.pmed.1000097. [DOI] [PMC free article] [PubMed]
  38. Pandor A, Goodacre S, Horner D, Stevens JW, Clowes M, Davis S, et al. Systematic Review and Cost-effectiveness Analysis of Thromboprophylaxis for Lower Limb Immobilisation. PROSPERO 2017: CRD42017058688. URL: www.crd.york.ac.uk/prospero/display_record.php?RecordID=58688 (accessed 3 April 2018).
  39. Higgins JPT, Sterne JAC, Savović J, Page MJ, Hróbjartsson A, Boutron I, et al. A revised tool for assessing risk of bias in randomized trials. Cochrane Database Syst Rev 2016;(Suppl. 1):29–31.
  40. Higgins JP, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 2011;343:d5928. https://doi.org/10.1136/bmj.d5928 doi: 10.1136/bmj.d5928. [DOI] [PMC free article] [PubMed]
  41. Hartling L, Hamm MP, Milne A, Vandermeer B, Santaguida PL, Ansari M, et al. Testing the risk of bias tool showed low reliability between individual reviewers and across consensus assessments of reviewer pairs. J Clin Epidemiol 2013;66:973–81. https://doi.org/10.1016/j.jclinepi.2012.07.005 doi: 10.1016/j.jclinepi.2012.07.005. [DOI] [PubMed]
  42. Hartling L, Ospina M, Liang Y, Dryden DM, Hooton N, Krebs Seida J, Klassen TP. Risk of bias versus quality assessment of randomised controlled trials: cross sectional study. BMJ 2009;339:b4012. https://doi.org/10.1136/bmj.b4012 doi: 10.1136/bmj.b4012. [DOI] [PMC free article] [PubMed]
  43. Jørgensen L, Paludan-Müller AS, Laursen DR, Savović J, Boutron I, Sterne JA, et al. Evaluation of the Cochrane tool for assessing risk of bias in randomized clinical trials: overview of published comments and analysis of user practice in Cochrane and non-Cochrane reviews. Syst Rev 2016;5:80. https://doi.org/10.1186/s13643-016-0259-8 doi: 10.1186/s13643-016-0259-8. [DOI] [PMC free article] [PubMed]
  44. Savović J, Weeks L, Sterne JA, Turner L, Altman DG, Moher D, Higgins JP. Evaluation of the Cochrane Collaboration’s tool for assessing the risk of bias in randomized trials: focus groups, online survey, proposed recommendations and their implementation. Syst Rev 2014;3:37. https://doi.org/10.1186/2046-4053-3-37 doi: 10.1186/2046-4053-3-37. [DOI] [PMC free article] [PubMed]
  45. Lunn D, Thomas A, Best N, Spiegelhalter D. WinBUGS – a Bayesian modelling framework: concepts, structure, and extensibility. Stat Comput 2000;10:325–37. https://doi.org/10.1023/A:1008929526011 doi: 10.1023/A:1008929526011. [DOI]
  46. Brooks SP, Gelman A. General methods for monitoring convergence of iterative simulations. J Comput Graph Stat 1998;7:434–55.
  47. Dias S, Sutton AJ, Welton NJ, Ades AE. NICE DSU Technical Support Document 3: Heterogeneity – Subgroups, Meta-Regression, Bias and Bias-Adjustment. Sheffield: Decision Support Unit; 2012. URL: www.nicedsu.org.uk (accessed 31 July 2018).
  48. Dias S, Sutton AJ, Welton NJ, Ades AE. NICE DSU Technical Support Document 2: A Generalised Linear Modelling Framework for Pairwise and Network Meta-Analysis of Randomised Controlled Trials. Sheffield: Decision Support Unit; 2016. URL: www.nicedsu.org.uk (accessed 31 July 2018). [PubMed]
  49. Bruntink MM, Groutars YME, Schipper IB, Breederveld RS, Tuinebreijer WE, Derksen RJ, PROTECT study group. Nadroparin or fondaparinux versus no thromboprophylaxis in patients immobilised in a below-knee plaster cast (PROTECT): a randomised controlled trial. Injury 2017;48:936–40. https://doi.org/10.1016/j.injury.2017.02.018 doi: 10.1016/j.injury.2017.02.018. [DOI] [PubMed]
  50. Goel DP, Buckley R, deVries G, Abelseth G, Ni A, Gray R. Prophylaxis of deep-vein thrombosis in fractures below the knee: a prospective randomised controlled trial. J Bone Joint Surg Br 2009;91:388–94. https://doi.org/10.1302/0301-620X.91B3.20820 doi: 10.1302/0301-620X.91B3.20820. [DOI] [PubMed]
  51. Jørgensen PS, Warming T, Hansen K, Paltved C, Vibeke Berg H, Jensen R, et al. Low molecular weight heparin (Innohep) as thromboprophylaxis in outpatients with a plaster cast: a venografic controlled study. Thromb Res 2002;105:477–80. https://doi.org/10.1016/S0049-3848(02)00059-2 doi: 10.1016/S0049-3848(02)00059-2. [DOI] [PubMed]
  52. Kock HJ, Schmit-Neuerburg KP, Hanke J, Rudofsky G, Hirche H. Thromboprophylaxis with low-molecular-weight heparin in outpatients with plaster-cast immobilisation of the leg. Lancet 1995;346:459–61. https://doi.org/10.1016/S0140-6736(95)91320-3 doi: 10.1016/S0140-6736(95)91320-3. [DOI] [PubMed]
  53. Kujath P, Spannagel U, Habscheid W. Incidence and prophylaxis of deep venous thrombosis in outpatients with injury of the lower limb. Haemostasis 1993;23(Suppl. 1):20–6. https://doi.org/10.1159/000216905 doi: 10.1159/000216905. [DOI] [PubMed]
  54. Lapidus LJ, Ponzer S, Elvin A, Levander C, Lärfars G, Rosfors S, de Bri E. Prolonged thromboprophylaxis with dalteparin during immobilization after ankle fracture surgery: a randomized placebo-controlled, double-blind study. Acta Orthop 2007;78:528–35. https://doi.org/10.1080/17453670710014185 doi: 10.1080/17453670710014185. [DOI] [PubMed]
  55. Lapidus LJ, Rosfors S, Ponzer S, Levander C, Elvin A, Lärfars G, de Bri E. Prolonged thromboprophylaxis with dalteparin after surgical treatment of Achilles tendon rupture: a randomized, placebo-controlled study. J Orthop Trauma 2007;21:52–7. https://doi.org/10.1097/01.bot.0000250741.65003.14 doi: 10.1097/01.bot.0000250741.65003.14. [DOI] [PubMed]
  56. Lassen MR, Borris LC, Nakov RL. Use of the low-molecular-weight heparin reviparin to prevent deep-vein thrombosis after leg injury requiring immobilization. N Engl J Med 2002;347:726–30. https://doi.org/10.1056/NEJMoa011327 doi: 10.1056/NEJMoa011327. [DOI] [PubMed]
  57. Samama CM, Lecoules N, Kierzek G, Claessens YE, Riou B, Rosencher N, et al. Comparison of fondaparinux with low molecular weight heparin for venous thromboembolism prevention in patients requiring rigid or semi-rigid immobilization for isolated non-surgical below-knee injury. J Thromb Haemost 2013;11:1833–43. https://doi.org/10.1111/jth.12395 doi: 10.1111/jth.12395. [DOI] [PubMed]
  58. Selby R, Geerts WH, Kreder HJ, Crowther MA, Kaus L, Sealey F, D-KAF (Dalteparin in Knee-to-Ankle Fracture) Investigators. A double-blind, randomized controlled trial of the prevention of clinically important venous thromboembolism after isolated lower leg fractures. J Orthop Trauma 2015;29:224–30. https://doi.org/10.1097/BOT.0000000000000250 doi: 10.1097/BOT.0000000000000250. [DOI] [PubMed]
  59. van Adrichem RA, Nemeth B, Algra A, le Cessie S, Rosendaal FR, Schipper IB, et al. Thromboprophylaxis after knee arthroscopy and lower-leg casting. N Engl J Med 2017;376:515–25. https://doi.org/10.1056/NEJMoa1613303 doi: 10.1056/NEJMoa1613303. [DOI] [PubMed]
  60. Zheng X, Li DY, Wangyang Y, Zhang XC, Guo KJ, Zhao FC, et al. Effect of chemical thromboprophylaxis on the rate of venous thromboembolism after treatment of foot and ankle fractures. Foot Ankle Int 2016;37:1218–24. https://doi.org/10.1177/1071100716658953 doi: 10.1177/1071100716658953. [DOI] [PubMed]
  61. Sterne JA, Hernán MA, Reeves BC, Savović J, Berkman ND, Viswanathan M, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ 2016;355:i4919. https://doi.org/10.1136/bmj.i4919 doi: 10.1136/bmj.i4919. [DOI] [PMC free article] [PubMed]
  62. Whiting PF, Rutjes AW, Westwood ME, Mallett S, Deeks JJ, Reitsma JB, et al. QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med 2011;155:529–36. https://doi.org/10.7326/0003-4819-155-8-201110180-00009 doi: 10.7326/0003-4819-155-8-201110180-00009. [DOI] [PubMed]
  63. Rowswell HR, Nokes TJC. Significant reduction in hospital-acquired thrombosis: impact of national risk assessment and real-time feedback. Open Heart 2017;4:e000653. https://doi.org/10.1136/openhrt-2017-000653 doi: 10.1136/openhrt-2017-000653. [DOI] [PMC free article] [PubMed]
  64. Hanslow SS, Grujic L, Slater HK, Chen D. Thromboembolic disease after foot and ankle surgery. Foot Ankle Int 2006;27:693–5. https://doi.org/10.1177/107110070602700907 doi: 10.1177/107110070602700907. [DOI] [PubMed]
  65. Ho E, Omari A. Prevalence of acute deep vein thrombosis in patients with ankle and foot fractures treated with nonoperative management – a pilot study. Int J Angiol 2017;26:53–9. https://doi.org/10.1055/s-0035-1556054 doi: 10.1055/s-0035-1556054. [DOI] [PMC free article] [PubMed]
  66. Jameson SS, Rankin KS, Desira NL, James P, Muller SD, Reed MR, Rangan A. Pulmonary embolism following ankle fractures treated without an operation – an analysis using National Health Service data. Injury 2014;45:1256–61. https://doi.org/10.1016/j.injury.2014.05.009 doi: 10.1016/j.injury.2014.05.009. [DOI] [PubMed]
  67. Manafi Rasi A, Kazemian G, Emami Moghadam M, Tavakoli Larestani R, Fallahi A, Nemati A, et al. Deep vein thrombosis following below knee immobilization: the need for chemoprophylaxis. Trauma Mon 2013;17:367–9. https://doi.org/10.5812/traumamon.9158 doi: 10.5812/traumamon.9158. [DOI] [PMC free article] [PubMed]
  68. Patel A, Ogawa B, Charlton T, Thordarson D. Incidence of deep vein thrombosis and pulmonary embolism after Achilles tendon rupture. Clin Orthop Relat Res 2012;470:270–4. https://doi.org/10.1007/s11999-011-2166-6 doi: 10.1007/s11999-011-2166-6. [DOI] [PMC free article] [PubMed]
  69. Riou B, Rothmann C, Lecoules N, Bouvat E, Bosson JL, Ravaud P, et al. Incidence and risk factors for venous thromboembolism in patients with nonsurgical isolated lower limb injuries. Am J Emerg Med 2007;25:502–8. https://doi.org/10.1016/j.ajem.2006.09.012 doi: 10.1016/j.ajem.2006.09.012. [DOI] [PubMed]
  70. van Adrichem RA, Debeij J, Nelissen RG, Schipper IB, Rosendaal FR, Cannegieter SC. Below-knee cast immobilization and the risk of venous thrombosis: results from a large population-based case-control study. J Thromb Haemost 2014;12:1461–9. https://doi.org/10.1111/jth.12655 doi: 10.1111/jth.12655. [DOI] [PubMed]
  71. Wahlsten LR, Eckardt H, Lyngbæk S, Jensen PF, Fosbøl EL, Torp-Pedersen C, et al. Symptomatic venous thromboembolism following fractures distal to the knee: a nationwide Danish cohort study. J Bone Joint Surg Am 2015;97:470–7. https://doi.org/10.2106/JBJS.N.00307 doi: 10.2106/JBJS.N.00307. [DOI] [PubMed]
  72. Saragas NP, Ferrao PN, Saragas E, Jacobson BF. The impact of risk assessment on the implementation of venous thromboembolism prophylaxis in foot and ankle surgery. Foot Ankle Surg 2014;20:85–9. https://doi.org/10.1016/j.fas.2013.11.002 doi: 10.1016/j.fas.2013.11.002. [DOI] [PubMed]
  73. Mizel MS, Temple HT, Michelson JD, Alvarez RG, Clanton TO, Frey CC, et al. Thromboembolism after foot and ankle surgery. A multicenter study. Clin Orthop Relat Res 1998;348:180–5. [PubMed]
  74. Selby R, Geerts WH, Kreder HJ, Crowther MA, Kaus L, Sealey F. Symptomatic venous thromboembolism uncommon without thromboprophylaxis after isolated lower-limb fracture: the Knee-to-Ankle Fracture (KAF) cohort study. J Bone Joint Surg Am 2014;96:e83. https://doi.org/10.2106/JBJS.M.00236 doi: 10.2106/JBJS.M.00236. [DOI] [PubMed]
  75. Centre for Reviews and Dissemination. Systematic Reviews. CRD’s Guidance for Undertaking Reviews in Health Care. York: Centre for Reviews and Dissemination, University of York; 2009. URL: www.york.ac.uk/crd/SysRev/!SSL!/WebHelp/SysRev3.htm (accessed 14 August 2017).
  76. Altman DG. Systematic reviews of evaluations of prognostic variables. BMJ 2001;323:224–8. https://doi.org/10.1136/bmj.323.7306.224 doi: 10.1136/bmj.323.7306.224. [DOI] [PMC free article] [PubMed]
  77. Moons KG, de Groot JA, Bouwmeester W, Vergouwe Y, Mallett S, Altman DG, et al. Critical appraisal and data extraction for systematic reviews of prediction modelling studies: the CHARMS checklist. PLOS Med 2014;11:e1001744. https://doi.org/10.1371/journal.pmed.1001744 doi: 10.1371/journal.pmed.1001744. [DOI] [PMC free article] [PubMed]
  78. Eingartner C, Hontzsch D, Lang E, Weller S. [Individualized prophylaxis for thromboembolism in outpatients – a practical way out between ‘ever’ and ‘never’?] Aktuelle Traumatologie 1995;25:1–5.
  79. Giannadakis K, Gehling H, Sitter H, Achenbach S, Hahne H, Gotzen L. [Is medicamentous thrombosis prophylaxis necessary in conservative outpatient therapy with lower limb injuries?] Unfallchirurg 2000;103:475–8. https://doi.org/10.1007/s001130050568 doi: 10.1007/s001130050568. [DOI] [PubMed]
  80. Haque S, Bishnoi A, Khairandish H, Menon D. Thromboprophylaxis in ambulatory trauma patients with foot and ankle fractures: prospective study using a risk scoring system. Foot Ankle Spec 2016;9:388–93. https://doi.org/10.1177/1938640016640892 doi: 10.1177/1938640016640892. [DOI] [PubMed]
  81. Saragas NP, Ferrao PN, Jacobson BF, Saragas E, Strydom A. The benefit of pharmacological venous thromboprophylaxis in foot and ankle surgery. S Afr Med J 2017;107:327–30. https://doi.org/10.7196/SAMJ.2017.v107i4.10843 doi: 10.7196/SAMJ.2017.v107i4.10843. [DOI] [PubMed]
  82. Watson U, Hickey BA, Jones HM, Perera A. A critical evaluation of venous thromboembolism risk assessment models used in patients with lower limb cast immobilisation. Foot Ankle Surg 2016;22:191–5. https://doi.org/10.1016/j.fas.2015.08.003 doi: 10.1016/j.fas.2015.08.003. [DOI] [PubMed]
  83. van Hylckama Vlieg A, Baglin CA, Luddington R, MacDonald S, Rosendaal FR, Baglin TP. The risk of a first and a recurrent venous thrombosis associated with an elevated D-dimer level and an elevated thrombin potential: results of the THE-VTE study. J Thromb Haemost 2015;13:1642–52. https://doi.org/10.1111/jth.13043 doi: 10.1111/jth.13043. [DOI] [PubMed]
  84. Ribeiro DD, Bucciarelli P, Braekkan SK, Lijfering WM, Passamonti SM, Brodin EE, et al. Seasonal variation of venous thrombosis: a consecutive case series within studies from Leiden, Milan and Tromsø. J Thromb Haemost 2012;10:1704–7. https://doi.org/10.1111/j.1538-7836.2012.04811.x doi: 10.1111/j.1538-7836.2012.04811.x. [DOI] [PubMed]
  85. Hasson F, Keeney S, McKenna H. Research guidelines for the Delphi survey technique. J Adv Nurs 2000;32:1008–15. [PubMed]
  86. Jones J, Hunter D. Consensus methods for medical and health services research. BMJ 1995;311:376–80. https://doi.org/10.1136/bmj.311.7001.376 doi: 10.1136/bmj.311.7001.376. [DOI] [PMC free article] [PubMed]
  87. McMillan SS, King M, Tully MP. How to use the nominal group and Delphi techniques. Int J Clin Pharm 2016;38:655–62. https://doi.org/10.1007/s11096-016-0257-x doi: 10.1007/s11096-016-0257-x. [DOI] [PMC free article] [PubMed]
  88. Crawford IW, Mackway-Jones K, Russell DR, Carley SD. Delphi based consensus study into planning for chemical incidents. Emerg Med J 2004;21:24–8. https://doi.org/10.1136/emj.2003.003087 doi: 10.1136/emj.2003.003087. [DOI] [PMC free article] [PubMed]
  89. Fuller GW, Nelson-Piercy C, Hunt BJ, Lecky FE, Thomas S, Horspool K, et al. Consensus-derived clinical decision rules to guide advanced imaging decisions for pulmonary embolism in pregnancy and the postpartum period. Eur J Emerg Med 2018;25:221–2. https://doi.org/10.1097/MEJ.0000000000000477 doi: 10.1097/MEJ.0000000000000477. [DOI] [PubMed]
  90. SmartSurvey Ltd. Make Smarter Decisions. URL: www.smartsurvey.co.uk/ (accessed 2 October 2017).
  91. Canadian Agency for Drugs and Technologies in Health (CADTH). Strings Attached: CADTH Database Search Filters. Ottawa, ON: CADTH; 2016. URL: www.cadth.ca/resources/finding-evidence (accessed 1 August 2017).
  92. Centre for Reviews and Dissemination. NHS Economic Evaluation Database Search Strategy. York: Centre for Reviews and Dissemination, University of York; 2014. URL: www.crd.york.ac.uk/crdweb/searchstrategies.asp (accessed 1 August 2017).
  93. McKinlay RJ, Wilczynski NL, Haynes RB, Hedges Team. Optimal search strategies for detecting cost and economic studies in EMBASE. BMC Health Serv Res 2006;6:67. https://doi.org/10.1186/1472-6963-6-67 doi: 10.1186/1472-6963-6-67. [DOI] [PMC free article] [PubMed]
  94. National Institute for Health and Care Excellence (NICE). Guide to the Methods of Technology Appraisal. London: NICE; 2013. [PubMed]
  95. Brasel KJ, Borgstrom DC, Weigelt JA. Cost-effective prevention of pulmonary embolus in high-risk trauma patients. J Trauma 1997;42:456–60. https://doi.org/10.1097/00005373-199703000-00013 doi: 10.1097/00005373-199703000-00013. [DOI] [PubMed]
  96. Lu JP, Knudson MM, Bir N, Kallet R, Atkinson K. Fondaparinux for prevention of venous thromboembolism in high-risk trauma patients: a pilot study. J Am Coll Surg 2009;209:589–94. https://doi.org/10.1016/j.jamcollsurg.2009.08.001 doi: 10.1016/j.jamcollsurg.2009.08.001. [DOI] [PubMed]
  97. Velmahos GC, Oh Y, McCombs J, Oder D. An evidence-based cost-effectiveness model on methods of prevention of posttraumatic venous thromboembolism. J Trauma 2000;49:1059–64. https://doi.org/10.1097/00005373-200012000-00014 doi: 10.1097/00005373-200012000-00014. [DOI] [PubMed]
  98. Wolowacz SE, Roskell NS, Plumb JM, Clemens A, Noack H, Robinson PA, et al. Economic evaluation of dabigatran etexilate for the prevention of venous thromboembolism in patients aged over 75 years or with moderate renal impairment undergoing total knee or hip replacement. Thromb Haemost 2010;103:360–71. https://doi.org/10.1160/TH09-08-0579 doi: 10.1160/TH09-08-0579. [DOI] [PubMed]
  99. Wolowacz SE, Roskell NS, Maciver F, Beard SM, Robinson PA, Plumb JM, et al. Economic evaluation of dabigatran etexilate for the prevention of venous thromboembolism after total knee and hip replacement surgery. Clin Ther 2009;31:194–212. https://doi.org/10.1016/j.clinthera.2009.01.001 doi: 10.1016/j.clinthera.2009.01.001. [DOI] [PubMed]
  100. Curtis L, Burns A. Unit Costs of Health and Social Care 2017. Canterbury: PSSRU, University of Kent; 2017.
  101. Hippisley-Cox J, Coupland C. Predicting risk of upper gastrointestinal bleed and intracranial bleed with anticoagulants: cohort study to derive and validate the QBleed scores. BMJ 2014;349:g4606. https://doi.org/10.1136/bmj.g4606 doi: 10.1136/bmj.g4606. [DOI] [PMC free article] [PubMed]
  102. Fang MC, Go AS, Chang Y, Hylek EM, Henault LE, Jensvold NG, Singer DE. Death and disability from warfarin-associated intracranial and extracranial hemorrhages. Am J Med 2007;120:700–5.https://doi.org/10.1016/j.amjmed.2006.07.034 doi: 10.1016/j.amjmed.2006.07.034. [DOI] [PMC free article] [PubMed]
  103. Button LA, Roberts SE, Evans PA, Goldacre MJ, Akbari A, Dsilva R, et al. Hospitalized incidence and case fatality for upper gastrointestinal bleeding from 1999 to 2007: a record linkage study. Aliment Pharmacol Ther 2011;33:64–76. https://doi.org/10.1111/j.1365-2036.2010.04495.x doi: 10.1111/j.1365-2036.2010.04495.x. [DOI] [PubMed]
  104. Kooiman J, van Hagen N, Iglesias Del Sol A, Planken EV, Lip GY, van der Meer FJ, et al. The HAS-BLED score identifies patients with acute venous thromboembolism at high risk of major bleeding complications during the first six months of anticoagulant treatment. PLOS ONE 2015;10:e0122520. https://doi.org/10.1371/journal.pone.0122520 doi: 10.1371/journal.pone.0122520. [DOI] [PMC free article] [PubMed]
  105. Nieto JA, Solano R, Ruiz-Ribó MD, Ruiz-Gimenez N, Prandoni P, Kearon C, Monreal M, RIETE Investigators. Fatal bleeding in patients receiving anticoagulant therapy for venous thromboembolism: findings from the RIETE registry. J Thromb Haemost 2010;8:1216–22. https://doi.org/10.1111/j.1538-7836.2010.03852.x doi: 10.1111/j.1538-7836.2010.03852.x. [DOI] [PubMed]
  106. Office for National Statistics. National Life Tables, England 1980–82 to 2014–16. Newport: Office for National Statistics; 2017.
  107. Fogelholm R, Murros K, Rissanen A, Avikainen S. Long term survival after primary intracerebral haemorrhage: a retrospective population based study. J Neurol Neurosurg Psychiatry 2005;76:1534–8. http://doi.org/10.1136/jnnp.2004.055145 doi: 10.1136/jnnp.2004.055145. [DOI] [PMC free article] [PubMed]
  108. Maestre A, Sánchez R, Rosa V, Aujesky D, Lorenzo A, Barillari G, Monreal M, RIETE Investigators. Clinical characteristics and outcome of inpatients versus outpatients with venous thromboembolism: findings from the RIETE Registry. Eur J Intern Med 2010;21:377–82. https://doi.org/10.1016/j.ejim.2010.07.004 doi: 10.1016/j.ejim.2010.07.004. [DOI] [PubMed]
  109. Hach-Wunderle V, Bauersachs R, Gerlach HE, Eberle S, Schellong S, Riess H, et al. Post-thrombotic syndrome 3 years after deep venous thrombosis in the Thrombosis and Pulmonary Embolism in Out-Patients (TULIPA) PLUS Registry. J Vasc Surg Venous Lymphat Disord 2013;1:5–12. https://doi.org/10.1016/j.jvsv.2012.07.003 doi: 10.1016/j.jvsv.2012.07.003. [DOI] [PubMed]
  110. van Dongen CJ, Prandoni P, Frulla M, Marchiori A, Prins MH, Hutten BA. Relation between quality of anticoagulant treatment and the development of the postthrombotic syndrome. J Thromb Haemost 2005;3:939–42. https://doi.org/10.1111/j.1538-7836.2005.01333.x doi: 10.1111/j.1538-7836.2005.01333.x. [DOI] [PubMed]
  111. Ende-Verhaar YM, Cannegieter SC, Vonk Noordegraaf A, Delcroix M, Pruszczyk P, Mairuhu AT, et al. Incidence of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism: a contemporary view of the published literature. Eur Respir J 2017;49:1601792. https://doi.org/10.1183/13993003.01792-2016 doi: 10.1183/13993003.01792-2016. [DOI] [PubMed]
  112. Pengo V, Lensing AW, Prins MH, Marchiori A, Davidson BL, Tiozzo F, et al. Incidence of chronic thromboembolic pulmonary hypertension after pulmonary embolism. N Engl J Med 2004;350:2257–64. https://doi.org/10.1056/NEJMoa032274 doi: 10.1056/NEJMoa032274. [DOI] [PubMed]
  113. Delcroix M, Lang I, Pepke-Zaba J, Jansa P, D’Armini AM, Snijder R, et al. Long-term outcome of patients with chronic thromboembolic pulmonary hypertension: results from an international prospective registry. Circulation 2016;133:859–71. https://doi.org/10.1161/CIRCULATIONAHA.115.016522 doi: 10.1161/CIRCULATIONAHA.115.016522. [DOI] [PubMed]
  114. Goodacre S, Horspool K, Shephard N, Pollard D, Hunt B, Fuller G, et al. Selecting pregnant or postpartum women with suspected pulmonary embolism for diagnostic imaging: the DiPEP diagnostic study with decision-analysis modelling. Health Technol Assess 2018;22(47). https://doi.org/10.3310/hta22470 doi: 10.3310/hta22470. [DOI] [PMC free article] [PubMed]
  115. Menakaya CU, Pennington N, Muthukumar N, Joel J, Ramirez Jimenez AJ, Shaw CJ, Mohsen A. The cost of outpatient venous thromboembolism prophylaxis following lower limb injuries. Bone Joint J 2013;95–B:673–7. https://doi.org/10.1302/0301-620X.95B5.30555 doi: 10.1302/0301-620X.95B5.30555. [DOI] [PubMed]
  116. Department of Health and Social Care. NHS Reference Costs 2015 to 2016. London: Department of Health and Social Care; 2016.
  117. Luengo-Fernandez R, Yiin GS, Gray AM, Rothwell PM. Population-based study of acute- and long-term care costs after stroke in patients with AF. Int J Stroke 2013;8:308–14. https://doi.org/10.1111/j.1747-4949.2012.00812.x doi: 10.1111/j.1747-4949.2012.00812.x. [DOI] [PMC free article] [PubMed]
  118. Jiménez D, de Miguel-Díez J, Guijarro R, Trujillo-Santos J, Otero R, Barba R, et al. Trends in the management and outcomes of acute pulmonary embolism: analysis from the RIETE registry. J Am Coll Cardiol 2016;67:162–70. https://doi.org/10.1016/j.jacc.2015.10.060 doi: 10.1016/j.jacc.2015.10.060. [DOI] [PubMed]
  119. Pollack CV, Schreiber D, Goldhaber SZ, Slattery D, Fanikos J, O’Neil BJ, et al. Clinical characteristics, management, and outcomes of patients diagnosed with acute pulmonary embolism in the emergency department: initial report of EMPEROR (Multicenter Emergency Medicine Pulmonary Embolism in the Real World Registry). J Am Coll Cardiol 2011;57:700–6. https://doi.org/10.1016/j.jacc.2010.05.071 doi: 10.1016/j.jacc.2010.05.071. [DOI] [PubMed]
  120. Rosand J, Eckman MH, Knudsen KA, Singer DE, Greenberg SM. The effect of warfarin and intensity of anticoagulation on outcome of intracerebral hemorrhage. Arch Intern Med 2004;164:880–4. https://doi.org/10.1001/archinte.164.8.880 doi: 10.1001/archinte.164.8.880. [DOI] [PubMed]
  121. Rockall TA, Logan RFA, Devlin HB, Northfield TC. Incidence of and mortality from acute upper gastrointestinal haemorrhage in the United Kingdom. BMJ 1995;311:222–6. https://doi.org/10.1136/bmj.311.6999.222 doi: 10.1136/bmj.311.6999.222. [DOI] [PMC free article] [PubMed]
  122. McPherson SJ, Mason MT, Smith, NCE, Kelly K, Ellis D, Mason M. Time to Get Control? A Review of the Care Received by Patients Who Had a Severe Gastrointestinal Haemorrhage. London: National Confidential Enquiry into Patient Outcome and Death; 2015.
  123. Cohen AT, Gitt AK, Bauersachs R, Fronk EM, Laeis P, Mismetti P, et al. The management of acute venous thromboembolism in clinical practice. Results from the European PREFER in VTE Registry. Thromb Haemost 2017;117:1326–37. https://doi.org/10.1160/TH16-10-0793 doi: 10.1160/TH16-10-0793. [DOI] [PMC free article] [PubMed]
  124. Carrier M, Le Gal G, Wells PS, Rodger MA. Systematic review: case-fatality rates of recurrent venous thromboembolism and major bleeding events among patients treated for venous thromboembolism. Ann Intern Med 2010;152:578–89. https://doi.org/10.7326/0003-4819-152-9-201005040-00008 doi: 10.7326/0003-4819-152-9-201005040-00008. [DOI] [PubMed]
  125. Galanaud JP, Monreal M, Kahn SR. Epidemiology of the post-thrombotic syndrome. Thromb Res 2018;164:100–9. https://doi.org/10.1016/j.thromres.2017.07.026 doi: 10.1016/j.thromres.2017.07.026. [DOI] [PubMed]
  126. Kahn SR, Partsch H, Vedantham S, Prandoni P, Kearon C, Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of post-thrombotic syndrome of the leg for use in clinical investigations: a recommendation for standardization. J Thromb Haemost 2009;7:879–83. https://doi.org/10.1111/j.1538-7836.2009.03294.x doi: 10.1111/j.1538-7836.2009.03294.x. [DOI] [PubMed]
  127. Persson LM, Lapidus LJ, Lärfars G, Rosfors S. Asymptomatic deep venous thrombosis is associated with a low risk of post-thrombotic syndrome. Eur J Vasc Endovasc Surg 2009;38:229–33. https://doi.org/10.1016/j.ejvs.2008.03.021 doi: 10.1016/j.ejvs.2008.03.021. [DOI] [PubMed]
  128. Schindler OS, Dalziel R. Post-thrombotic syndrome after total hip or knee arthroplasty: incidence in patients with asymptomatic deep venous thrombosis. J Orthop Surg 2005;13:113–19. https://doi.org/10.1177/230949900501300202 doi: 10.1177/230949900501300202. [DOI] [PubMed]
  129. Prandoni P, Villalta S, Bagatella P, Rossi L, Marchiori A, Piccioli A, et al. The clinical course of deep-vein thrombosis. Prospective long-term follow-up of 528 symptomatic patients. Haematologica 1997;82:423–8. [PubMed]
  130. National Institute for Health and Care Excellence (NICE). Venous Thromboembolism in Over 16s – Reducing the Risk of Hospital-acquired Deep Vein Thrombosis or Pulmonary Embolism: Draft NICE Guideline for Consultation. London: NICE; 2017.
  131. Copley V, Pickett K, Cooper K, Shepherd J. Rivaroxaban for the Treatment of Pulmonary Embolism and the Prevention of Recurrent Venous Thromboembolism: Evidence Review Group Report. London: NICE; 2012.
  132. Edwards S, Wakefield V, Thurgar E, Karner C, Marceniuk G. Dabigatran Etexilate for the Treatment and Secondary Prevention of Deep Vein Thrombosis and/or Pulmonary Embolism: A Single Technology Appraisal – Evidence Review Group Report. London: NICE; 2014.
  133. Greenhalgh J, Bagust A, Beale S, Boland A, Richardson M, Dwan K, et al. Apixaban for the Treatment and Secondary Prevention of Deep Vein Thrombosis and/or Pulmonary Embolism: Evidence Review Group Report. London: NICE; 2014.
  134. Holmes M, Carroll C, Papaioannou D. Dabigatran Etexilate for the Prevention of Venous Thromboembolism in Patients Undergoing Elective Hip and Knee Surgery: A Single Technology Appraisal – Evidence Review Group Report. London: NICE; 2008. doi: 10.3310/hta13suppl2/08. [DOI] [PubMed]
  135. Riemsma R, Joore M, Grutters J, Armstrong N, Misso K, Noake C, et al. Apixaban for the Prevention of Venous Thromboembolism in People Undergoing Elective Knee and Hip Replacement Surgery: Evidence Review Group Report. London: NICE; 2011.
  136. Stevenson M, Scope A, Holmes M, Rees A, Kaltenthaler E. Rivaroxaban for the prevention of venous thromboembolism: a single technology appraisal. Health Technol Assess 2009;13(Suppl. 3). https://doi.org/10.3310/hta13suppl3/07 doi: 10.3310/hta13suppl3/07. [DOI] [PubMed]
  137. Bristol-Myers Squibb Company, Pfizer Inc. Apixaban (Eliquis®) for the Prevention of Venous Thromboembolic Events in Adult Patients Who Have Undergone Elective Hip or Knee Replacement Surgery: Company Submission. London: NICE; 2011.
  138. Bristol-Myers Squibb Company, Pfizer Inc. Apixaban (Eliquis®) for the Treatment of Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE) and Prevention of Recurrent DVT and PE in Adults: Company Submission. London: NICE; 2014.
  139. Bayer Schering Pharma AG. Single Technology Appraisal (STA) of Rivaroxaban (Xarelto®) for the Prevention of Venous Thromboemobolism (VTE) in Adult Patients Undergoing Elective Hip or Knee Replacement Surgery: Company Submission. London: NICE; 2008.
  140. National Institute for Health and Care Excellence. Edoxaban Tosylate for the Treatment and Secondary Prevention of Deep Vein Thrombosis and/or Pulmonary Embolism. [TA354]. London: NICE; 2015.
  141. Fernando SM, Reardon PM, Dowlatshahi D, English SW, Thavorn K, Tanuseputro P, et al. Outcomes and costs of patients admitted to the ICU due to spontaneous intracranial hemorrhage. Crit Care Med 2018;46:e395–e403. https://doi.org/10.1097/CCM.0000000000003013 doi: 10.1097/CCM.0000000000003013. [DOI] [PubMed]
  142. Ashrani AA, Heit JA. Incidence and cost burden of post-thrombotic syndrome. J Thromb Thrombolysis 2009;28:465–76. https://doi.org/10.1007/s11239-009-0309-3 doi: 10.1007/s11239-009-0309-3. [DOI] [PMC free article] [PubMed]
  143. Grosse SD, Nelson RE, Nyarko KA, Richardson LC, Raskob GE. The economic burden of incident venous thromboembolism in the United States: a review of estimated attributable healthcare costs. Thromb Res 2016;137:3–10. https://doi.org/10.1016/j.thromres.2015.11.033 doi: 10.1016/j.thromres.2015.11.033. [DOI] [PMC free article] [PubMed]
  144. Prandoni P. Healthcare burden associated with the post-thrombotic syndrome and potential impact of the new oral anticoagulants. Eur J Haematol 2012;88:185–94. https://doi.org/10.1111/j.1600-0609.2011.01733.x doi: 10.1111/j.1600-0609.2011.01733.x. [DOI] [PubMed]
  145. Ruppert A, Steinle T, Lees M. Economic burden of venous thromboembolism: a systematic review. J Med Econ 2011;14:65–74. https://doi.org/10.3111/13696998.2010.546465 doi: 10.3111/13696998.2010.546465. [DOI] [PubMed]
  146. Caprini JA, Botteman MF, Stephens JM, Nadipelli V, Ewing MM, Brandt S, et al. Economic burden of long-term complications of deep vein thrombosis after total hip replacement surgery in the United States. Value Health 2003;6:59–74. https://doi.org/10.1046/j.1524-4733.2003.00204.x doi: 10.1046/j.1524-4733.2003.00204.x. [DOI] [PubMed]
  147. MacDougall DA, Feliu AL, Boccuzzi SJ, Lin J. Economic burden of deep-vein thrombosis, pulmonary embolism, and post-thrombotic syndrome. Am J Health Syst Pharm 2006;63(Suppl. 20):5–15. https://doi.org/10.2146/ajhp060388 doi: 10.2146/ajhp060388. [DOI] [PubMed]
  148. Olin JW, Beusterien KM, Childs MB, Seavey C, McHugh L, Griffiths RI. Medical costs of treating venous stasis ulcers: evidence from a retrospective cohort study. Vasc Med 1999;4:1–7. https://doi.org/10.1177/1358836X9900400101 doi: 10.1177/1358836X9900400101. [DOI] [PubMed]
  149. Ramacciotti E, Gomes M, de Aguiar ET, Caiafa JS, de Moura LK, Araújo GR, et al. A cost analysis of the treatment of patients with post-thrombotic syndrome in Brazil. Thromb Res 2006;118:699–704. https://doi.org/10.1016/j.thromres.2005.12.005 doi: 10.1016/j.thromres.2005.12.005. [DOI] [PubMed]
  150. Bergqvist D, Jendteg S, Johansen L, Persson U, Odegaard K. Cost of long-term complications of deep venous thrombosis of the lower extremities: an analysis of a defined patient population in Sweden. Ann Intern Med 1997;126:454–7. https://doi.org/10.7326/0003-4819-126-6-199703150-00006 doi: 10.7326/0003-4819-126-6-199703150-00006. [DOI] [PubMed]
  151. Guanella R, Ducruet T, Johri M, Miron MJ, Roussin A, Desmarais S, et al. Economic burden and cost determinants of deep vein thrombosis during 2 years following diagnosis: a prospective evaluation. J Thromb Haemost 2011;9:2397–405. https://doi.org/10.1111/j.1538-7836.2011.04516.x doi: 10.1111/j.1538-7836.2011.04516.x. [DOI] [PubMed]
  152. Goodacre S, Sampson F, Stevenson M, Wailoo A, Sutton A, Thomas S, et al. Measurement of the clinical and cost-effectiveness of non-invasive diagnostic testing strategies for deep vein thrombosis. Health Technol Assess 2006;10(15). https://doi.org/10.3310/hta10150 doi: 10.3310/hta10150. [DOI] [PubMed]
  153. Cohen ABM, Nadipelli V, Stephens J, Ewing M, Collier P, et al. Estimating the Economic Burden of PTS and Recurrent VTE Following DVT in the UK. Paper presented at the XVIII Congress of the International Society on Thrombosis and Haemostasis, Paris, 6 July 2001.
  154. Harnan S, Rafia R, Poku E, Stevens JW, Stevenson M, Wong R. Rivaroxaban for the Treatment of Deep Vein Thrombosis and Secondary Prevention of Venous Thromboembolism. London: NICE; 2012.
  155. Kirson NY, Birnbaum HG, Ivanova JI, Waldman T, Joish V, Williamson T. Excess costs associated with patients with chronic thromboembolic pulmonary hypertension in a US privately insured population. Appl Health Econ Health Policy 2011;9:377–87. https://doi.org/10.2165/11592440-000000000-00000 doi: 10.2165/11592440-000000000-00000. [DOI] [PubMed]
  156. Arverud ED, Anundsson P, Hardell E, Barreng G, Edman G, Latifi A, et al. Ageing, deep vein thrombosis and male gender predict poor outcome after acute Achilles tendon rupture. Bone Joint J 2016;98–B:1635–41. https://doi.org/10.1302/0301-620X.98B12.BJJ-2016-0008.R1 doi: 10.1302/0301-620X.98B12.BJJ-2016-0008.R1. [DOI] [PubMed]
  157. Dolan P. Modeling valuations for EuroQol health states. Med Care 1997;35:1095–108. https://doi.org/10.1097/00005650-199711000-00002 doi: 10.1097/00005650-199711000-00002. [DOI] [PubMed]
  158. Hedner E, Carlsson J, Kulich KR, Stigendal L, Ingelgård A, Wiklund I. An instrument for measuring health-related quality of life in patients with deep venous thrombosis (DVT): development and validation of Deep Venous Thrombosis Quality of Life (DVTQOL) questionnaire. Health Qual Life Outcomes 2004;2:30. https://doi.org/10.1186/1477-7525-2-30 doi: 10.1186/1477-7525-2-30. [DOI] [PMC free article] [PubMed]
  159. Lubberts B, Paulino Pereira NR, Kabrhel C, Kuter DJ, DiGiovanni CW. What is the effect of venous thromboembolism and related complications on patient reported health-related quality of life? A meta-analysis. Thromb Haemost 2016;116:417–31. https://doi.org/10.1160/TH16-02-0152 doi: 10.1160/TH16-02-0152. [DOI] [PubMed]
  160. Haig Y, Enden T, Grøtta O, Kløw NE, Slagsvold CE, Ghanima W, et al. Post-thrombotic syndrome after catheter-directed thrombolysis for deep vein thrombosis (CaVenT): 5-year follow-up results of an open-label, randomised controlled trial. Lancet Haematol 2016;3:e64–71. https://doi.org/10.1016/S2352-3026(15)00248-3 doi: 10.1016/S2352-3026(15)00248-3. [DOI] [PubMed]
  161. Ware JE, Sherbourne CD. The MOS 36-item short-form health survey (SF-36): I. Conceptual framework and item selection. Med Care 1992;30:473–83. https://doi.org/10.1097/00005650-199206000-00002 doi: 10.1097/00005650-199206000-00002. [DOI] [PubMed]
  162. Harzheim D, Klose H, Pinado FP, Ehlken N, Nagel C, Fischer C, et al. Anxiety and depression disorders in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. Respir Res 2013;14:104. https://doi.org/10.1186/1465-9921-14-104 doi: 10.1186/1465-9921-14-104. [DOI] [PMC free article] [PubMed]
  163. Hogg K, Shaw J, Coyle D, Fallah P, Carrier M, Wells P. Validity of standard gamble estimated quality of life in acute venous thrombosis. Thromb Res 2014;134:819–25. https://doi.org/10.1016/j.thromres.2014.07.029 doi: 10.1016/j.thromres.2014.07.029. [DOI] [PubMed]
  164. Kline JA, Nordenholz KE, Courtney DM, Kabrhel C, Jones AE, Rondina MT, et al. Treatment of submassive pulmonary embolism with tenecteplase or placebo: cardiopulmonary outcomes at 3 months – multicenter double-blind, placebo-controlled randomized trial. J Thromb Haemost 2014;12:459–68. https://doi.org/10.1111/jth.12521 doi: 10.1111/jth.12521. [DOI] [PubMed]
  165. Mathias SD, Prebil LA, Putterman CG, Chmiel JJ, Throm RC, Comerota AJ. A health-related quality of life measure in patients with deep vein thrombosis: a validation study. Drug Inf J 1999;33:1173–87. https://doi.org/10.1177/009286159903300421 doi: 10.1177/009286159903300421. [DOI]
  166. O’Brien B, Levine M, Willan A, Goeree R, Haley S, Blackhouse G, Gent M. Economic evaluation of outpatient treatment with low-molecular-weight heparin for proximal vein thrombosis. Arch Intern Med 1999;159:2298–304. https://doi.org/10.1001/archinte.159.19.2298 doi: 10.1001/archinte.159.19.2298. [DOI] [PubMed]
  167. Roman A, Barbera JA, Castillo MJ, Muñoz R, Escribano P. Health-related quality of life in a national cohort of patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension. Arch Bronconeumol 2013;49:181–8. https://doi.org/10.1016/j.arbres.2012.12.007 doi: 10.1016/j.arbres.2012.12.007. [DOI] [PubMed]
  168. Shrier I, Kahn SR, Steele RJ. Effect of early physical activity on long-term outcome after venous thrombosis. Clin J Sport Med 2009;19:487–93. https://doi.org/10.1097/JSM.0b013e3181bd11a3 doi: 10.1097/JSM.0b013e3181bd11a3. [DOI] [PubMed]
  169. Stewart LK, Peitz GW, Nordenholz KE, Courtney DM, Kabrhel C, Jones AE, et al. Contribution of fibrinolysis to the physical component summary of the SF-36 after acute submassive pulmonary embolism. J Thromb Thrombolysis 2015;40:161–6. https://doi.org/10.1007/s11239-014-1155-5 doi: 10.1007/s11239-014-1155-5. [DOI] [PMC free article] [PubMed]
  170. Roberts LN, Patel RK, Donaldson N, Bonner L, Arya R. Post-thrombotic syndrome is an independent determinant of health-related quality of life following both first proximal and distal deep vein thrombosis. Haematologica 2014;99:e41–3. https://doi.org/10.3324/haematol.2013.089870 doi: 10.3324/haematol.2013.089870. [DOI] [PMC free article] [PubMed]
  171. van Es J, den Exter PL, Kaptein AA, Andela CD, Erkens PM, Klok FA, et al. Quality of life after pulmonary embolism as assessed with SF-36 and PEmb-QoL. Thromb Res 2013;132:500–5. https://doi.org/10.1016/j.thromres.2013.06.016 doi: 10.1016/j.thromres.2013.06.016. [DOI] [PubMed]
  172. Lukas PS, Krummenacher R, Biasiutti FD, Begré S, Znoj H, von Känel R. Association of fatigue and psychological distress with quality of life in patients with a previous venous thromboembolic event. Thromb Haemost 2009;102:1219–26. https://doi.org/10.1160/TH09-05-0316 doi: 10.1160/TH09-05-0316. [DOI] [PubMed]
  173. Cohen AT, Bauersachs R, Gitt AK, Mismetti P, Monreal M, Willich SN, et al. Health state in patients with venous thromboembolism on conventional and non-VKA oral anticoagulants as assessed with the EQ-5D-5L questionnaire: PREFER in VTE registry. Value Health 2014;17:A493–4. https://doi.org/10.1016/j.jval.2014.08.1465 doi: 10.1016/j.jval.2014.08.1465. [DOI] [PubMed]
  174. Sullivan P, Fraessdorf M, Feuring M, Schulman S, Hass B. Health-related quality of life after venous thromboembolism. Value Health 2011;14:A384. https://doi.org/10.1016/j.jval.2011.08.830 doi: 10.1016/j.jval.2011.08.830. [DOI]
  175. Tavoly M, Utne KK, Jelsness-Jørgensen LP, Wik HS, Klok FA, Sandset PM, Ghanima W. Health-related quality of life after pulmonary embolism: a cross-sectional study. BMJ Open 2016;6:e013086. https://doi.org/10.1136/bmjopen-2016-013086 doi: 10.1136/bmjopen-2016-013086. [DOI] [PMC free article] [PubMed]
  176. Hogg K, Kimpton M, Carrier M, Coyle D, Forgie M, Wells P. Estimating quality of life in acute venous thrombosis. JAMA Intern Med 2013;173:1067–72. https://doi.org/10.1001/jamainternmed.2013.563 doi: 10.1001/jamainternmed.2013.563. [DOI] [PubMed]
  177. Locadia M, Bossuyt PM, Stalmeier PF, Sprangers MA, van Dongen CJ, Middeldorp S, et al. Treatment of venous thromboembolism with vitamin K antagonists: patients’ health state valuations and treatment preferences. Thromb Haemost 2004;92:1336–41. https://doi.org/10.1160/TH04-02-0075 doi: 10.1160/TH04-02-0075. [DOI] [PubMed]
  178. Daiichi Sankyo. Edoxaban for the Treatment and Secondary Prevention of Deep Vein Thrombosis and/or Pulmonary Embolism. Company Submission. London: NICE; 2015.
  179. Utne KK, Tavoly M, Wik HS, Jelsness-Jørgensen LP, Holst R, Sandset PM, Ghanima W. Health-related quality of life after deep vein thrombosis. SpringerPlus 2016;5:1278. https://doi.org/10.1186/s40064-016-2949-z doi: 10.1186/s40064-016-2949-z. [DOI] [PMC free article] [PubMed]
  180. Kahn SR, Shbaklo H, Lamping DL, Holcroft CA, Shrier I, Miron MJ, et al. Determinants of health-related quality of life during the 2 years following deep vein thrombosis. J Thromb Haemost 2008;6:1105–12. https://doi.org/10.1111/j.1538-7836.2008.03002.x doi: 10.1111/j.1538-7836.2008.03002.x. [DOI] [PubMed]
  181. Kahn SR, Elman EA, Bornais C, Blostein M, Wells PS. Post-thrombotic syndrome, functional disability and quality of life after upper extremity deep venous thrombosis in adults. Thromb Haemost 2005;93:499–502. https://doi.org/10.1160/TH04-10-0640 doi: 10.1160/TH04-10-0640. [DOI] [PubMed]
  182. Czihal M, Paul S, Rademacher A, Bernau C, Hoffmann U. Impact of the postthrombotic syndrome on quality of life after primary upper extremity deep venous thrombosis. Vasa 2012;41:200–4. https://doi.org/10.1024/0301-1526/a000186 doi: 10.1024/0301-1526/a000186. [DOI] [PubMed]
  183. Berzaczy D, Popovic M, Reiter M, Puchner S, Weber M, Minar E, et al. Quality of life in patients with idiopathic subclavian vein thrombosis. Thromb Res 2010;125:25–8. https://doi.org/10.1016/j.thromres.2009.04.015 doi: 10.1016/j.thromres.2009.04.015. [DOI] [PubMed]
  184. Broholm R, Sillesen H, Damsgaard MT, Jørgensen M, Just S, Jensen LP, et al. Postthrombotic syndrome and quality of life in patients with iliofemoral venous thrombosis treated with catheter-directed thrombolysis. J Vasc Surg 2011;5(6 Suppl.):18–25. https://doi.org/10.1016/j.jvs.2011.06.021 doi: 10.1016/j.jvs.2011.06.021. [DOI] [PubMed]
  185. Kahn SR, Hirsch A, Shrier I. Effect of postthrombotic syndrome on health-related quality of life after deep venous thrombosis. Arch Intern Med 2002;162:1144–8. https://doi.org/10.1001/archinte.162.10.1144 doi: 10.1001/archinte.162.10.1144. [DOI] [PubMed]
  186. Kahn SR, Hirsch A, Shrier I. Predictors of the post-thrombotic syndrome during long-term treatment of proximal deep vein thrombosis. J Thromb Haemost 2005;3:718–23. https://doi.org/10.1111/j.1538-7836.2005.01216.x doi: 10.1111/j.1538-7836.2005.01216.x. [DOI] [PubMed]
  187. Zhang X, Ren Q, Jiang X, Sun J, Gong J, Tang B, et al. A prospective randomized trial of catheter-directed thrombolysis with additional balloon dilatation for iliofemoral deep venous thrombosis: A single-center experience. Cardiovasc Interv Radiol 2014;37:958–68. https://doi.org/10.1007/s00270-013-0747-3 doi: 10.1007/s00270-013-0747-3. [DOI] [PubMed]
  188. Kahn SR, Shrier I, Shapiro S, Houweling AH, Hirsch AM, Reid RD, et al. Six-month exercise training program to treat post-thrombotic syndrome: A randomized controlled two-centre trial. Canad Med Assoc J 2011;183:37–44. https://doi.org/10.1503/cmaj.100248 doi: 10.1503/cmaj.100248. [DOI] [PMC free article] [PubMed]
  189. Enden T, Wik HS, Kvam AK, Haig Y, Kløw NE, Sandset PM. Health-related quality of life after catheter-directed thrombolysis for deep vein thrombosis: secondary outcomes of the randomised, non-blinded, parallel-group CaVenT study. BMJ Open 2013;3:e002984. https://doi.org/10.1136/bmjopen-2013-002984 doi: 10.1136/bmjopen-2013-002984. [DOI] [PMC free article] [PubMed]
  190. Lenert LA, Soetikno RM. Automated computer interviews to elicit utilities: potential applications in the treatment of deep venous thrombosis. J Am Med Inform Assoc 1997;4:49–56. https://doi.org/10.1136/jamia.1997.0040049 doi: 10.1136/jamia.1997.0040049. [DOI] [PMC free article] [PubMed]
  191. O’Meara JJ, McNutt RA, Evans AT, Moore SW, Downs SM. A decision analysis of streptokinase plus heparin as compared with heparin alone for deep-vein thrombosis. N Engl J Med 1994;330:1864–9. https://doi.org/10.1056/NEJM199406303302605 doi: 10.1056/NEJM199406303302605. [DOI] [PubMed]
  192. O’Donnell MJ, McRae S, Kahn SR, Julian JA, Kearon C, Mackinnon B, et al. Evaluation of a venous-return assist device to treat severe post-thrombotic syndrome (VENOPTS): a randomized controlled trial. Thromb Haemost 2008;99:623–9. https://doi.org/10.1160/TH07-09-0546 doi: 10.1160/TH07-09-0546. [DOI] [PubMed]
  193. Holmes CE, Bambace NM, Lewis P, Callas PW, Cushman M. Efficacy of a short course of complex lymphedema therapy or graduated compression stocking therapy in the treatment of post-thrombotic syndrome. Vasc Med 2014;19:42–8. https://doi.org/10.1177/1358863X14521883 doi: 10.1177/1358863X14521883. [DOI] [PubMed]
  194. Ara R, Brazier JE. Using health state utility values from the general population to approximate baselines in decision analytic models when condition-specific data are not available. Value Health 2011;14:539–45. https://doi.org/10.1016/j.jval.2010.10.029 doi: 10.1016/j.jval.2010.10.029. [DOI] [PubMed]
  195. Ghofrani HA, D’Armini AM, Grimminger F, Hoeper MM, Jansa P, Kim NH, et al. Riociguat for the treatment of chronic thromboembolic pulmonary hypertension. N Engl J Med 2013;369:319–29. https://doi.org/10.1056/NEJMoa1209657 doi: 10.1056/NEJMoa1209657. [DOI] [PubMed]
  196. Olschewski H, Simonneau G, Galiè N, Higenbottam T, Naeije R, Rubin LJ, et al. Inhaled iloprost for severe pulmonary hypertension. N Engl J Med 2002;347:322–9. https://doi.org/10.1056/NEJMoa020204 doi: 10.1056/NEJMoa020204. [DOI] [PubMed]
  197. Keogh AM, McNeil KD, Wlodarczyk J, Gabbay E, Williams TJ. Quality of life in pulmonary arterial hypertension: improvement and maintenance with bosentan. J Heart Lung Transplant 2007;26:181–7. https://doi.org/10.1016/j.healun.2006.11.009 doi: 10.1016/j.healun.2006.11.009. [DOI] [PubMed]
  198. Meads DM, McKenna SP, Doughty N, Das C, Gin-Sing W, Langley J, Pepke-Zaba J. The responsiveness and validity of the CAMPHOR Utility Index. Eur Respir J 2008;32:1513–19. https://doi.org/10.1183/09031936.00069708 doi: 10.1183/09031936.00069708. [DOI] [PubMed]
  199. Shafazand S, Goldstein MK, Doyle RL, Hlatky MA, Gould MK. Health-related quality of life in patients with pulmonary arterial hypertension. Chest 2004;126:1452–9. https://doi.org/10.1378/chest.126.5.1452 doi: 10.1378/chest.126.5.1452. [DOI] [PubMed]
  200. Lindgren P, Kahan T, Poulter N, Buxton M, Svarvar P, Dahlöf B, Jonsson B, ASCOT investigators. Utility loss and indirect costs following cardiovascular events in hypertensive patients: the ASCOT health economic substudy. Eur J Health Econ 2007;8:25–30. https://doi.org/10.1007/s10198-006-0002-9 doi: 10.1007/s10198-006-0002-9. [DOI] [PubMed]
  201. Luengo-Fernandez R, Gray AM, Bull L, Welch S, Cuthbertson F, Rothwell PM, Oxford Vascular Study. Quality of life after TIA and stroke: ten-year results of the Oxford Vascular Study. Neurology 2013;81:1588–95. https://doi.org/10.1212/WNL.0b013e3182a9f45f doi: 10.1212/WNL.0b013e3182a9f45f. [DOI] [PMC free article] [PubMed]
  202. Lunde L. Can EQ-5D and 15D be used interchangeably in economic evaluations? Assessing quality of life in post-stroke patients. Eur J Health Econ 2013;14:539–50. https://doi.org/10.1007/s10198-012-0402-y doi: 10.1007/s10198-012-0402-y. [DOI] [PubMed]
  203. Pickard AS, Johnson JA, Feeny DH, Shuaib A, Carriere KC, Nasser AM. Agreement between patient and proxy assessments of health-related quality of life after stroke using the EQ-5D and Health Utilities Index. Stroke 2004;35:607–12. https://doi.org/10.1161/01.STR.0000110984.91157.BD doi: 10.1161/01.STR.0000110984.91157.BD. [DOI] [PubMed]
  204. Rivero-Arias O, Ouellet M, Gray A, Wolstenholme J, Rothwell PM, Luengo-Fernandez R. Mapping the modified Rankin scale (mRS) measurement into the generic EuroQol (EQ-5D) health outcome. Med Decis Making 2010;30:341–54. https://doi.org/10.1177/0272989X09349961 doi: 10.1177/0272989X09349961. [DOI] [PubMed]
  205. Gage BF, Cardinalli AB, Owens DK. The effect of stroke and stroke prophylaxis with aspirin or warfarin on quality of life. Arch Intern Med 1996;156:1829–36. https://doi.org/10.1001/archinte.1996.00440150083009 doi: 10.1001/archinte.1996.00440150083009. [DOI] [PubMed]
  206. Robinson A, Thomson R, Parkin D, Sudlow M, Eccles M. How patients with atrial fibrillation value different health outcomes: a standard gamble study. J Health Serv Res Policy 2001;6:92–8. https://doi.org/10.1258/1355819011927288 doi: 10.1258/1355819011927288. [DOI] [PubMed]
  207. Marchetti M, Pistorio A, Barone M, Serafini S, Barosi G. Low-molecular-weight heparin versus warfarin for secondary prophylaxis of venous thromboembolism: a cost-effectiveness analysis. Am J Med 2001;111:130–9. https://doi.org/10.1016/S0002-9343(01)00793-8 doi: 10.1016/S0002-9343(01)00793-8. [DOI] [PubMed]
  208. Monz BU, Connolly SJ, Korhonen M, Noack H, Pooley J. Assessing the impact of dabigatran and warfarin on health-related quality of life: results from an RE-LY sub-study. Int J Cardiol 2013;168:2540–7. https://doi.org/10.1016/j.ijcard.2013.03.059 doi: 10.1016/j.ijcard.2013.03.059. [DOI] [PubMed]
  209. Strong M, Brennan A, Oakley J. How to calculate value of information in seconds using ‘SAVI’, the Sheffield Accelerated Value of Information web app. Value Health 2015;18:A725–6. https://doi.org/10.1016/j.jval.2015.09.2759 doi: 10.1016/j.jval.2015.09.2759. [DOI]
  210. Caprini JA, Arcelus JI, Reyna JJ. Effective risk stratification of surgical and nonsurgical patients for venous thromboembolic disease. Semin Hematol 2001;38(Suppl. 2):12–19. https://doi.org/10.1016/S0037-1963(01)90094-0 doi: 10.1016/S0037-1963(01)90094-0. [DOI] [PubMed]
  211. Department of Health and Social Care. Venous Thromboembolism (VTE) Risk Assessment. London: Department of Health and Social Care; 2010.
  212. Nygaard A, Nelson AS, Pick A, Danekas PL, Massoomi F, Thielen J, et al. Inter-rater reliability in the evaluation of a thrombosis risk assessment tool. Hospital Pharmacy 2009;44:1089–94. https://doi.org/10.1310/hpj4412-1089 doi: 10.1310/hpj4412-1089. [DOI]
  213. Lijmer JG, Mol BW, Heisterkamp S, Bonsel GJ, Prins MH, van der Meulen JH, Bossuyt PM. Empirical evidence of design-related bias in studies of diagnostic tests. JAMA 1999;282:1061–6. https://doi.org/10.1001/jama.282.11.1061 doi: 10.1001/jama.282.11.1061. [DOI] [PubMed]
  214. Gómez-Outes A, Terleira-Fernández AI, Suárez-Gea ML, Vargas-Castrillón E. Dabigatran, rivaroxaban, or apixaban versus enoxaparin for thromboprophylaxis after total hip or knee replacement: systematic review, meta-analysis, and indirect treatment comparisons. BMJ 2012;344:e3675. https://doi.org/10.1136/bmj.e3675 doi: 10.1136/bmj.e3675. [DOI] [PMC free article] [PubMed]
  215. Lassen MR, Ageno W, Borris LC, Lieberman JR, Rosencher N, Bandel TJ, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med 2008;358:2776–86. https://doi.org/10.1056/NEJMoa076016 doi: 10.1056/NEJMoa076016. [DOI] [PubMed]
  216. Lassen MR, Raskob GE, Gallus A, Pineo G, Chen D, Portman RJ. Apixaban or enoxaparin for thromboprophylaxis after knee replacement. N Engl J Med 2009;361:594–604. https://doi.org/10.1056/NEJMoa0810773 doi: 10.1056/NEJMoa0810773. [DOI] [PubMed]
  217. López-Reyes R, Nauffal D, Ballester M, Martín-Antorán JM, de Sousa MS, Riera-Mestre A, et al. Venous thromboembolism in patients immobilised at home. Eur Respir J 2015;45:1728–31. https://doi.org/10.1183/09031936.00220114 doi: 10.1183/09031936.00220114. [DOI] [PubMed]
  218. Blackwell JR, Raval P, Quigley JP, Patel A, McBride D. Patient compliance with venous thromboembolism prophylaxis (VTE). J Clin Orthop Trauma 2017;8:201–5. https://doi.org/10.1016/j.jcot.2017.03.009 doi: 10.1016/j.jcot.2017.03.009. [DOI] [PMC free article] [PubMed]
  219. Calder JD, Freeman R, Domeij-Arverud E, van Dijk CN, Ackermann PW. Meta-analysis and suggested guidelines for prevention of venous thromboembolism (VTE) in foot and ankle surgery. Knee Surg Sports Traumatol Arthrosc 2016;24:1409–20. https://doi.org/10.1007/s00167-015-3976-y doi: 10.1007/s00167-015-3976-y. [DOI] [PMC free article] [PubMed]
  220. Chapelle C, Rosencher N, Jacques Zufferey P, Mismetti P, Cucherat M, Laporte S, Meta-Embol Group. Prevention of venous thromboembolic events with low-molecular-weight heparin in the non-major orthopaedic setting: meta-analysis of randomized controlled trials. Arthroscopy 2014;30:987–96. https://doi.org/10.1016/j.arthro.2014.03.009 doi: 10.1016/j.arthro.2014.03.009. [DOI] [PubMed]
  221. Doggrell SA. Reviparin as prophylaxis for thromboembolism after leg injury and hip replacement. Expert Opin Pharmacother 2003;4:285–8. https://doi.org/10.1517/14656566.4.2.285 doi: 10.1517/14656566.4.2.285. [DOI] [PubMed]
  222. Griffiths JT, Matthews L, Pearce CJ, Calder JD. Incidence of venous thromboembolism in elective foot and ankle surgery with and without aspirin prophylaxis. J Bone Joint Surg Br 2012;94:210–14. https://doi.org/10.1302/0301-620X.94B2.27579 doi: 10.1302/0301-620X.94B2.27579. [DOI] [PubMed]
  223. Haque S, Davies MB. Oral thromboprophylaxis in patients with ankle fractures immobilized in a below the knee cast. Foot Ankle Surg 2015;21:266–8. https://doi.org/10.1016/j.fas.2015.02.002 doi: 10.1016/j.fas.2015.02.002. [DOI] [PubMed]
  224. Hickey BA, Watson U, Cleves A, Alikhan R, Pugh N, Nokes L, et al. Does thromboprophylaxis reduce symptomatic venous thromboembolism in patients with below knee cast treatment for foot and ankle trauma? A systematic review and meta-analysis. Foot and Ankle Surgery 2018;24:19–27. https://doi.org/10.1016/j.fas.2016.06.005 doi: 10.1016/j.fas.2016.06.005. [DOI] [PubMed]
  225. Kaye ID, Patel DN, Strauss EJ, Alaia MJ, Garofolo G, Martinez A, Jazrawi LM. Prevention of venous thromboembolism after arthroscopic knee surgery in a low-risk population with the use of aspirin. A randomized trial. Bull Hosp Jt Dis 2015;73:243–8. [PubMed]
  226. Kock HJ, Schmit-Neuerburg KP, Hanke J, Hakmann A, Althoff M, Rudofsky G, Hirche H. [Ambulatory prevention of thrombosis with low molecular weight heparin in plaster immobilization of the lower extremity.] Chirurg 1993;64:483–91. [PubMed]
  227. Little MTM. Low-molecular-weight heparin did not differ from placebo in preventing clinically important deep venous thrombosis after surgical repair of leg fracture. J Bone Joint Surg Am 2016;98:316. https://doi.org/10.2106/JBJS.15.01442 doi: 10.2106/JBJS.15.01442. [DOI] [PubMed]
  228. Mangwani J, Sheikh N, Cichero M, Williamson D. What is the evidence for chemical thromboprophylaxis in foot and ankle surgery? Systematic review of the English literature. Foot 2015;25:173–8. https://doi.org/10.1016/j.foot.2014.07.007 doi: 10.1016/j.foot.2014.07.007. [DOI] [PubMed]
  229. Menakaya CU, Boddice T, Malhotra R, Ingoe H, Shah M, Muthukumar N, et al. Outpatients thromboprophylaxis following lower limb immobilisation: an institution’s experience. Eur Orthopaed Traumatol 2013;5:335–9. https://doi.org/10.1007/s12570-013-0240-0 doi: 10.1007/s12570-013-0240-0. [DOI]
  230. Metz R, Verleisdonk EJ, van der Heijden GJ. Insufficient evidence for routine use of thromboprophylaxis in ambulatory patients with an isolated lower leg injury requiring immobilization: results of a meta-analysis. Eur J Trauma Emerg Surg 2009;35:169–75. https://doi.org/10.1007/s00068-008-8015-y doi: 10.1007/s00068-008-8015-y. [DOI] [PubMed]
  231. Ramos J, Perrotta C, Badariotti G, Berenstein G. Interventions for preventing venous thromboembolism in adults undergoing knee arthroscopy. Cochrane Database Syst Rev 2008;4:CD005259. https://doi.org/10.1002/14651858.CD005259.pub3 doi: 10.1002/14651858.CD005259.pub3. [DOI] [PubMed]
  232. Samama CM, Lecoules N, Kierzek G, Claessens YE, Riou B, Rosencher N, et al. Comparison of fondaparinux with low-molecular-weight heparin for venous thromboembolism prevention in patients requiring rigid or semi-rigid immobilization for isolated non-surgical below-knee injury. Ann Fr Med ’Urg 2014;4:153–66. doi: 10.1111/jth.12395. [DOI] [PubMed]
  233. Samama CM, Riou B, Roy PM, Sautet A, Mismetti P. Prevention of venous thromboembolism after an isolated, non-surgical below-knee injury. Benefit/risk of fondaparinux vs. low molecular weight heparin: the FONDACAST study. J Thromb Haemost 2013;11:5. doi: 10.1111/jth.12395. [DOI] [PubMed]
  234. Samama CM, Riou B, Roy PM, Sautet A, Mismetti P, Van Der Veen A. Subgroup analysis of the FONDACAST study comparing fondaparinux to low-molecular-weight heparin for the prevention of venous thromboembolism after an isolated, non-surgical below-knee injury. J Thromb Haemost 2013;11:88–9. doi: 10.1111/jth.12395. [DOI] [PubMed]
  235. Spannagel U, Kujath P. Low molecular weight heparin for the prevention of thromboembolism in outpatients immobilized by plaster cast. Semin Thromb Hemost 1993;19(Suppl. 1):131–41. [PubMed]
  236. Walenga JM, Kaiser PC, Prechel MM, Hoppensteadt D, Jeske WP, Misselwitz F, et al. Sustained release of tissue factor following thrombosis of lower limb trauma. Clin Appl Thromb Hemost 2014;20:678–86. https://doi.org/10.1177/1076029614545212 doi: 10.1177/1076029614545212. [DOI] [PubMed]
  237. Ajwani SH, Shaw A, Naiz O, Bhaskar D, Charalambous CP. Venous thromboembolism prophylaxis in outpatient lower limb fractures and injuries. Ortop Traumatol Rehabil 2016;18:263–8. https://doi.org/10.5604/15093492.1212870 doi: 10.5604/15093492.1212870. [DOI] [PubMed]
  238. Batra S, Kurup H, Gul A, Andrew JG. Thromboprophylaxis following cast immobilisation for lower limb injuries – survey of current practice in United Kingdom. Injury 2006;37:813–17. https://doi.org/10.1016/j.injury.2006.03.016 doi: 10.1016/j.injury.2006.03.016. [DOI] [PubMed]
  239. Bertoletti L, Righini M, Bounameaux H, López-Jiménez L, Tiraferri E, Visonà A, et al. Acute venous thromboembolism after non-major orthopaedic surgery or post-traumatic limb immobilisation. Findings from the RIETE registry. Thromb Haemost 2011;105:739–41. https://doi.org/10.1160/TH10-11-0751 doi: 10.1160/TH10-11-0751. [DOI] [PubMed]
  240. Caprini JA. Identification of patient venous thromboembolism risk across the continuum of care. Clin Appl Thromb Hemost 2011;17:590–9. https://doi.org/10.1177/1076029611404217 doi: 10.1177/1076029611404217. [DOI] [PubMed]
  241. Cirlincione AS, Mendicino R, Catanzariti AR, Grossman J. Low-molecular-weight heparin for deep vein thrombosis prophylaxis in foot and ankle surgery: a review. J Foot Ankle Surg 2001;40:96–100. https://doi.org/10.1016/S1067-2516(01)80050-8 doi: 10.1016/S1067-2516(01)80050-8. [DOI] [PubMed]
  242. Decramer A, Lowyck H, Demuynck M. Parameters influencing thromboprophylaxis management of a lower leg trauma treated with a cast/splint. Acta Orthop Belg 2008;74:672–7. [PubMed]
  243. Douna F. Minor injuries as a risk factor for venous thrombosis. Medecine Therapeutique – Cardio 2008;4:129–32. doi: 10.1001/archinternmed.2007.5. [DOI] [PubMed]
  244. Dyall L, Munireddy S, Tams L, Strong J, Best A, Pavord S. Venous-thromboembolism in patients with plaster casts for lower leg fracture: experience in a large teaching hospital trust. Br J Haematol 2012;157:41.
  245. Engbers MJ, Blom JW, Cushman M, Rosendaal FR, Van Hylckama Vlieg A. The contribution of immobility risk factors to the risk of venous thrombosis in the older population. J Thromb Haemost 2013;11:440–1. doi: 10.1111/jth.12480. [DOI] [PubMed]
  246. Fall AO, Proulle V, Sall A, Mbaye A, Ba PS, Diao M, et al. Risk factors for thrombosis in an African population. Clin Med Insights Blood Disord 2014;7:1–6. https://doi.org/10.4137/CMBD.S13401 doi: 10.4137/CMBD.S13401. [DOI] [PMC free article] [PubMed]
  247. Felcher AH, Mularski RA, Mosen DM, Kimes TM, DeLoughery TG, Laxson SE. Incidence and risk factors for venous thromboembolic disease in podiatric surgery. Chest 2009;135:917–22. https://doi.org/10.1378/chest.08-1631 doi: 10.1378/chest.08-1631. [DOI] [PubMed]
  248. Fleischer AE, Abicht BP, Baker JR, Boffeli TJ, Jupiter DC, Schade VL. American College of Foot and Ankle Surgeons’ clinical consensus statement: risk, prevention, and diagnosis of venous thromboembolism disease in foot and ankle surgery and injuries requiring immobilization. J Foot Ankle Surg 2015;54:497–507. https://doi.org/10.1053/j.jfas.2015.02.022 doi: 10.1053/j.jfas.2015.02.022. [DOI] [PubMed]
  249. Gearhart MM, Luchette FA, Proctor MC, Lutomski DM, Witsken C, James L, et al. The risk assessment profile score identifies trauma patients at risk for deep vein thrombosis. Surgery 2000;128:631–40. https://doi.org/10.1067/msy.2000.108224 doi: 10.1067/msy.2000.108224. [DOI] [PubMed]
  250. Healy B, Beasley R, Weatherall M. Venous thromboembolism following prolonged cast immobilisation for injury to the tendo Achillis. J Bone Joint Surg Br 2010;92:646–50. https://doi.org/10.1302/0301-620X.92B5.23241 doi: 10.1302/0301-620X.92B5.23241. [DOI] [PubMed]
  251. Jiang Y, Li J, Liu Y, Li YC, Zhang WG. Risk factors for deep vein thrombosis after orthopedic surgery and the diagnostic value of D-dimer. Ann Vasc Surg 2015;29:675–81. https://doi.org/10.1016/j.avsg.2014.12.022 doi: 10.1016/j.avsg.2014.12.022. [DOI] [PubMed]
  252. Kocialkowski C, Bhosale A, Pillai A. Venous thromboembolism prophylaxis in patients immobilised in plaster casts. Clin Res Foot Ankle 2016;4:203. https://doi.org/10.4172/2329-910X.1000203 doi: 10.4172/2329-910X.1000203. [DOI]
  253. Lawall H, Matthiessen A, Hohmann V, Bramlage P, Haas S, Schellong S. Venous thromboembolism in medical outpatients – a cross-sectional survey of risk assessment and prophylaxis. Thromb Haemost 2011;105:190–6. https://doi.org/10.1160/TH10-03-0191 doi: 10.1160/TH10-03-0191. [DOI] [PubMed]
  254. Lim TK, Goh XL, Tay HC, Goh HFJ, Kang YK. Evaluation of risk assessment models (padua and caprini) in the prediction of venous thromboembolism events: a retrospective review. Ann Acad Med Singapore 2016;45:S90.
  255. Micheli LJ. Thromboembolic complications of cast immobilization for injuries of the lower extremities. Clin Orthop Relat Res 1975;108:191–5. https://doi.org/10.1097/00003086-197505000-00031 doi: 10.1097/00003086-197505000-00031. [DOI] [PubMed]
  256. Nemeth B, Van Adrichem RA, Le Cessie S, Van Hylckama Vlieg A, Bucciarelli P, et al. Prediction of risk of venous thrombosis after cast immobilization of the lower extremity. J Thromb Haemost 2013;11:438–9.
  257. Nesheiwat F, Sergi AR. Deep venous thrombosis and pulmonary embolism following cast immobilization of the lower extremity. J Foot Ankle Surg 1996;35:590–4. https://doi.org/10.1016/S1067-2516(96)80135-9 doi: 10.1016/S1067-2516(96)80135-9. [DOI] [PubMed]
  258. Park MS, Perkins SE, Spears GM, Ashrani AA, Leibson CL, Boos CM, et al. Risk factors for venous thromboembolism after acute trauma: a population-based case-cohort study. Thromb Res 2016;144:40–5. https://doi.org/10.1016/j.thromres.2016.03.026 doi: 10.1016/j.thromres.2016.03.026. [DOI] [PMC free article] [PubMed]
  259. Park SJ, Kim CK, Park YS, Moon YW, Lim SJ, Kim SM. Incidence and factors predicting venous thromboembolism after surgical treatment of fractures below the hip. J Orthop Trauma 2015;29:e349–54. https://doi.org/10.1097/BOT.0000000000000336 doi: 10.1097/BOT.0000000000000336. [DOI] [PubMed]
  260. Parsonage I. Venous thromboembolism in patients with below-knee plaster casts. Emerg Nurse 2009;16:32–5. https://doi.org/10.7748/en2009.03.16.10.32.c6852 doi: 10.7748/en2009.03.16.10.32.c6852. [DOI] [PubMed]
  261. Persson A, Wredmark T. The treatment of total ruptures of the Achilles tendon by plaster immobilisation. Int Orthop 1979;3:149–52. doi: 10.1007/BF00266886. [DOI] [PubMed]
  262. Randelli F, Romanini E, Biggi F, Danelli G, Della Rocca G, Laurora NR, et al. II Italian intersociety consensus statement on antithrombotic prophylaxis in orthopaedics and traumatology: arthroscopy, traumatology, leg immobilization, minor orthopaedic procedures and spine surgery. J Orthop Traumatol 2013;14:1–13. https://doi.org/10.1007/s10195-012-0214-y doi: 10.1007/s10195-012-0214-y. [DOI] [PMC free article] [PubMed]
  263. Rogers FB, Shackford SR, Horst MA, Miller JA, Wu D, Bradburn E, et al. Determining venous thromboembolic risk assessment for patients with trauma: the Trauma Embolic Scoring System. J Trauma Acute Care Surg 2012;73:511–15. https://doi.org/10.1097/TA.0b013e3182588b54 doi: 10.1097/TA.0b013e3182588b54. [DOI] [PubMed]
  264. Samama MM. An epidemiologic study of risk factors for deep vein thrombosis in medical outpatients: the Sirius study. Arch Intern Med 2000;160:3415–20. https://doi.org/10.1001/archinte.160.22.3415 doi: 10.1001/archinte.160.22.3415. [DOI] [PubMed]
  265. Simon MA, Mass DP, Zarins CK, Bidani N, Gudas CJ, Metz CE. The effect of a thigh tourniquet on the incidence of deep venous thrombosis after operations on the fore part of the foot. J Bone Joint Surg Am 1982;64:188–91. https://doi.org/10.2106/00004623-198264020-00006 doi: 10.2106/00004623-198264020-00006. [DOI] [PubMed]
  266. Slaybaugh RS, Beasley BD, Massa EG. Deep venous thrombosis risk assessment, incidence, and prophylaxis in foot and ankle surgery. Clin Podiatr Med Surg 2003;20:269–89. https://doi.org/10.1016/S0891-8422(03)00007-7 doi: 10.1016/S0891-8422(03)00007-7. [DOI] [PubMed]
  267. Solis G, Saxby T. Incidence of DVT following surgery of the foot and ankle. Foot Ankle Int 2002;23:411–14. https://doi.org/10.1177/107110070202300507 doi: 10.1177/107110070202300507. [DOI] [PubMed]
  268. Spencer FA, Emery C, Joffe SW, Pacifico L, Lessard D, Reed G, et al. Incidence rates, clinical profile, and outcomes of patients with venous thromboembolism. The Worcester VTE study. J Thromb Thrombolysis 2009;28:401–9. https://doi.org/10.1007/s11239-009-0378-3 doi: 10.1007/s11239-009-0378-3. [DOI] [PMC free article] [PubMed]
  269. Spyropoulos AC. Venous thromboembolism risk factors in acutely ill hospitalized medical patients. Haematologica Meeting Reports 2009;3:21–2.
  270. Spyropoulos AC, Anderson FA, FitzGerald G, Decousus H, Tapson V. Venous Thromboembolism Risk Factors in Acutely Ill Hospitalized Medical Patients: Findings From the Improve Registry (OC-MO-052). 22nd Congress of the International Society of Thrombosis and Haemostasis, Boston, MA, 11–16 July 2009. Abstract no. 6587, p. 122.
  271. Tan L, Qi B, Yu T, Wang C. Incidence and risk factors for venous thromboembolism following surgical treatment of fractures below the hip: a meta-analysis. Int Wound J 2016;13:1359–71. https://doi.org/10.1111/iwj.12533 doi: 10.1111/iwj.12533. [DOI] [PMC free article] [PubMed]
  272. Toure AO. Risk factors of thrombosis in an African population. J Thromb Haemost 2014;12:62.
  273. True VL, Williamson DM. Do patients receive the appropriate assessment and implementation of venous thromboembolism prophylaxis for lower leg trauma and surgery? Br J Haematol 2014;165:34.
  274. van Adrichem RA, Nelissen RG, Schipper IB, Rosendaal FR, Cannegieter SC. Risk of venous thrombosis after arthroscopy of the knee: results from a large population-based case-control study. J Thromb Haemost 2015;13:1441–8. https://doi.org/10.1111/jth.12996 doi: 10.1111/jth.12996. [DOI] [PubMed]
  275. van Adrichem RA, Debeij J, Nelissen GHH, Schipper IB, Rosendaal FR, Cannegieter SC. Lower leg cast immobilisation and risk of venous thrombosis: results from the MEGA study. J Thromb Haemost 2013;11:68.
  276. Vollans S, Chaturvedi A, Sivasankaran K, Madhu T, Hadland Y, Allgar V, Sharma HK. Symptomatic venous thromboembolism following circular frame treatment for tibial fractures. Injury 2015;46:1108–11. https://doi.org/10.1016/j.injury.2015.04.003 doi: 10.1016/j.injury.2015.04.003. [DOI] [PubMed]
  277. Wang J, Zhao CP, Wei J, Wang CM. An analysis of risk factors for lower limb deep venous thrombosis in patients with tibial plateau fractures. Chin J Bone Joint 2015;2:86–90.
  278. Simpson EL, Stevenson MD, Rawdin A, Papaioannou D. Thrombophilia testing in people with venous thromboembolism: systematic review and cost-effectiveness analysis. Health Technol Assess 2009;13(2). https://doi.org/10.3310/hta13020 doi: 10.3310/hta13020. [DOI] [PubMed]
  279. Ingelgard A, Hedner E, Stigendal J, Carlsson J. Patient-reported Outcomes in Patients with Deep Vein Thrombosis Treated with Warfarin. Paper presented at the 17th International Congress on Thrombosis, Bologna, 2002.
  280. Ghanima W, Wik HS, Tavoly M, Enden T, Jelsness-Jorgensen LP. Late consequences of venous thromboembolism: measuring quality of life after deep vein thrombosis and pulmonary embolism. Thromb Res 2018;164:170–6. https://doi.org/10.1016/j.thromres.2017.07.025 doi: 10.1016/j.thromres.2017.07.025. [DOI] [PubMed]

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