Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Prevention of venous thromboembolic disease in acutely ill hospitalized medical adults

Menaka Pai, MD, FRCPC
James D Douketis, MD, FRCPC, FACP, FCCP
Section Editors
Lawrence LK Leung, MD
Jess Mandel, MD
Deputy Editor
Geraldine Finlay, MD


It is estimated that over half of hospitalized medical patients are at risk for venous thromboembolism (VTE, ie, deep vein thrombosis [DVT] and/or pulmonary embolus [PE]) [1]. In addition, it is widely believed that PE is the most common preventable cause of hospital death [2-8].

This topic review discusses the prevention of VTE in patients hospitalized for acute medical illnesses [9]. Approaches to the prevention of VTE in surgical patients and patients with cancer and stroke, as well as in pregnancy are presented separately. (See "Prevention of venous thromboembolic disease in surgical patients" and "Medical complications of stroke", section on 'VTE prophylaxis' and "Risk and prevention of venous thromboembolism in adults with cancer" and "Deep vein thrombosis and pulmonary embolism in pregnancy: Prevention".)


While many epidemiologic studies report venous thromboembolism (VTE) rates, in the absence of prophylaxis, that range from 10 to 80 percent, these rates are likely overestimated [2,3,5,10-26].

Accurate estimates of the incidence of clinically meaningful venous thromboembolic disease (ie, pulmonary embolus [PE] and deep vein thrombosis [DVT]) in hospitalized medical patients have been hampered by factors including the derivation of data from mixed surgical and medical populations, the reporting of both symptomatic and asymptomatic events, the increasing use of thromboprophylaxis and early ambulation during hospital admission, and the trend toward reducing length of hospital stay.

Thromboprophylaxis has been shown to reduce the risk of VTE in hospitalized medical and surgical patients. While thromboprophylaxis has been reported to reduce the risk of death in surgical patients [27,28], most studies and a meta-analysis have not been able to show a consistent beneficial effect of thromboprophylaxis on mortality in hospitalized medical patients [29-37]. The reasons for this difference between medical and surgical patients are unclear but may be related to a greater number of comorbidities in medical patients that contribute to overall deaths. In addition, clinicians should be aware that VTE prophylaxis does not eliminate the risk of VTE or VTE-related death in hospitalized patients.  

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: Jul 20, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Anderson FA Jr, Zayaruzny M, Heit JA, et al. Estimated annual numbers of US acute-care hospital patients at risk for venous thromboembolism. Am J Hematol 2007; 82:777.
  2. Lindblad B, Eriksson A, Bergqvist D. Autopsy-verified pulmonary embolism in a surgical department: analysis of the period from 1951 to 1988. Br J Surg 1991; 78:849.
  3. Stein PD, Henry JW. Prevalence of acute pulmonary embolism among patients in a general hospital and at autopsy. Chest 1995; 108:978.
  4. White RH, Zhou H, Romano PS. Incidence of symptomatic venous thromboembolism after different elective or urgent surgical procedures. Thromb Haemost 2003; 90:446.
  5. Sandler DA, Martin JF. Autopsy proven pulmonary embolism in hospital patients: are we detecting enough deep vein thrombosis? J R Soc Med 1989; 82:203.
  6. Martino MA, Borges E, Williamson E, et al. Pulmonary embolism after major abdominal surgery in gynecologic oncology. Obstet Gynecol 2006; 107:666.
  7. Dismuke SE, Wagner EH. Pulmonary embolism as a cause of death. The changing mortality in hospitalized patients. JAMA 1986; 255:2039.
  8. Horlander KT, Mannino DM, Leeper KV. Pulmonary embolism mortality in the United States, 1979-1998: an analysis using multiple-cause mortality data. Arch Intern Med 2003; 163:1711.
  9. Dobromirski M, Cohen AT. How I manage venous thromboembolism risk in hospitalized medical patients. Blood 2012; 120:1562.
  10. Heit JA, O'Fallon WM, Petterson TM, et al. Relative impact of risk factors for deep vein thrombosis and pulmonary embolism: a population-based study. Arch Intern Med 2002; 162:1245.
  11. Prandoni P, Samama MM. Risk stratification and venous thromboprophylaxis in hospitalized medical and cancer patients. Br J Haematol 2008; 141:587.
  12. Caprini JA, Arcelus JI, Reyna JJ. Effective risk stratification of surgical and nonsurgical patients for venous thromboembolic disease. Semin Hematol 2001; 38:12.
  13. Gangireddy C, Rectenwald JR, Upchurch GR, et al. Risk factors and clinical impact of postoperative symptomatic venous thromboembolism. J Vasc Surg 2007; 45:335.
  14. Haas SK, Hach-Wunderle V, Mader FH, et al. An evaluation of venous thromboembolic risk in acutely ill medical patients immobilized at home: the AT-HOME Study. Clin Appl Thromb Hemost 2007; 13:7.
  15. Anderson FA Jr, Spencer FA. Risk factors for venous thromboembolism. Circulation 2003; 107:I9.
  16. Samama MM. An epidemiologic study of risk factors for deep vein thrombosis in medical outpatients: the Sirius study. Arch Intern Med 2000; 160:3415.
  17. Memtsoudis SG, Della Valle AG, Besculides MC, et al. Risk factors for perioperative mortality after lower extremity arthroplasty: a population-based study of 6,901,324 patient discharges. J Arthroplasty 2010; 25:19.
  18. Cohen AT, Alikhan R, Arcelus JI, et al. Assessment of venous thromboembolism risk and the benefits of thromboprophylaxis in medical patients. Thromb Haemost 2005; 94:750.
  19. Chopard P, Spirk D, Bounameaux H. Identifying acutely ill medical patients requiring thromboprophylaxis. J Thromb Haemost 2006; 4:915.
  20. Zakai NA, Wright J, Cushman M. Risk factors for venous thrombosis in medical inpatients: validation of a thrombosis risk score. J Thromb Haemost 2004; 2:2156.
  21. Cook D, Crowther M, Meade M, et al. Deep venous thrombosis in medical-surgical critically ill patients: prevalence, incidence, and risk factors. Crit Care Med 2005; 33:1565.
  22. Samama MM, Dahl OE, Quinlan DJ, et al. Quantification of risk factors for venous thromboembolism: a preliminary study for the development of a risk assessment tool. Haematologica 2003; 88:1410.
  23. Osborne NH, Wakefield TW, Henke PK. Venous thromboembolism in cancer patients undergoing major surgery. Ann Surg Oncol 2008; 15:3567.
  24. McColl MD, Walker ID, Greer IA. Risk factors for venous thromboembolism in pregnancy. Curr Opin Pulm Med 1999; 5:227.
  25. Walker MC, Garner PR, Keely EJ, et al. Changes in activated protein C resistance during normal pregnancy. Am J Obstet Gynecol 1997; 177:162.
  26. Heit JA, Melton LJ 3rd, Lohse CM, et al. Incidence of venous thromboembolism in hospitalized patients vs community residents. Mayo Clin Proc 2001; 76:1102.
  27. Collins R, Scrimgeour A, Yusuf S, Peto R. Reduction in fatal pulmonary embolism and venous thrombosis by perioperative administration of subcutaneous heparin. Overview of results of randomized trials in general, orthopedic, and urologic surgery. N Engl J Med 1988; 318:1162.
  28. Prevention of fatal postoperative pulmonary embolism by low doses of heparin. An international multicentre trial. Lancet 1975; 2:45.
  29. Samama MM, Cohen AT, Darmon JY, et al. A comparison of enoxaparin with placebo for the prevention of venous thromboembolism in acutely ill medical patients. Prophylaxis in Medical Patients with Enoxaparin Study Group. N Engl J Med 1999; 341:793.
  30. Hull RD, Schellong SM, Tapson VF, et al. Extended-duration venous thromboembolism prophylaxis in acutely ill medical patients with recently reduced mobility: a randomized trial. Ann Intern Med 2010; 153:8.
  31. Halkin H, Goldberg J, Modan M, Modan B. Reduction of mortality in general medical in-patients by low-dose heparin prophylaxis. Ann Intern Med 1982; 96:561.
  32. Gärdlund B. Randomised, controlled trial of low-dose heparin for prevention of fatal pulmonary embolism in patients with infectious diseases. The Heparin Prophylaxis Study Group. Lancet 1996; 347:1357.
  33. Mahé I, Bergmann JF, d'Azémar P, et al. Lack of effect of a low-molecular-weight heparin (nadroparin) on mortality in bedridden medical in-patients: a prospective randomised double-blind study. Eur J Clin Pharmacol 2005; 61:347.
  34. Kakkar AK, Cimminiello C, Goldhaber SZ, et al. Low-molecular-weight heparin and mortality in acutely ill medical patients. N Engl J Med 2011; 365:2463.
  35. Lederle FA, Zylla D, MacDonald R, Wilt TJ. Venous thromboembolism prophylaxis in hospitalized medical patients and those with stroke: a background review for an American College of Physicians Clinical Practice Guideline. Ann Intern Med 2011; 155:602.
  36. Lester W, Freemantle N, Begaj I, et al. Fatal venous thromboembolism associated with hospital admission: a cohort study to assess the impact of a national risk assessment target. Heart 2013; 99:1734.
  37. Heit JA, Crusan DJ, Ashrani AA, et al. Effect of a near-universal hospitalization-based prophylaxis regimen on annual number of venous thromboembolism events in the US. Blood 2017; 130:109.
  38. Spyropoulos AC, Anderson FA Jr, Fitzgerald G, et al. Predictive and associative models to identify hospitalized medical patients at risk for VTE. Chest 2011; 140:706.
  39. Khouli H, Shapiro J, Pham VP, et al. Efficacy of deep venous thrombosis prophylaxis in the medical intensive care unit. J Intensive Care Med 2006; 21:352.
  40. Laporte S, Mismetti P. Epidemiology of thrombotic risk factors: the difficulty in using clinical trials to develop a risk assessment model. Crit Care Med 2010; 38:S10.
  41. Ortel TL. Acquired thrombotic risk factors in the critical care setting. Crit Care Med 2010; 38:S43.
  42. Wu C, Lee AY. Malignancy and venous thrombosis in the critical care patient. Crit Care Med 2010; 38:S64.
  43. Castellucci LA, Wells PS, Duffett L. Nonleg venous thrombosis in critically ill adults. JAMA 2015; 313:411.
  44. Lim W, Meade M, Lauzier F, et al. Failure of anticoagulant thromboprophylaxis: risk factors in medical-surgical critically ill patients*. Crit Care Med 2015; 43:401.
  45. Ho KM, Chavan S, Pilcher D. Omission of early thromboprophylaxis and mortality in critically ill patients: a multicenter registry study. Chest 2011; 140:1436.
  46. Sørensen HT, Horvath-Puho E, Søgaard KK, et al. Arterial cardiovascular events, statins, low-dose aspirin and subsequent risk of venous thromboembolism: a population-based case-control study. J Thromb Haemost 2009; 7:521.
  47. Glynn RJ, Danielson E, Fonseca FA, et al. A randomized trial of rosuvastatin in the prevention of venous thromboembolism. N Engl J Med 2009; 360:1851.
  48. Ramcharan AS, Van Stralen KJ, Snoep JD, et al. HMG-CoA reductase inhibitors, other lipid-lowering medication, antiplatelet therapy, and the risk of venous thrombosis. J Thromb Haemost 2009; 7:514.
  49. Rabinowich L, Steinvil A, Leshem-Rubinow E, et al. Adherence to statins is associated with reduced incidence of idiopathic venous thromboembolism: real-life data from a large healthcare maintenance organisation. Heart 2012; 98:1817.
  50. Ray JG, Mamdani M, Tsuyuki RT, et al. Use of statins and the subsequent development of deep vein thrombosis. Arch Intern Med 2001; 161:1405.
  51. Herrington DM, Vittinghoff E, Lin F, et al. Statin therapy, cardiovascular events, and total mortality in the Heart and Estrogen/Progestin Replacement Study (HERS). Circulation 2002; 105:2962.
  52. Lacut K, Oger E, Le Gal G, et al. Statins but not fibrates are associated with a reduced risk of venous thromboembolism: a hospital-based case-control study. Fundam Clin Pharmacol 2004; 18:477.
  53. Khemasuwan D, Divietro ML, Tangdhanakanond K, et al. Statins decrease the occurrence of venous thromboembolism in patients with cancer. Am J Med 2010; 123:60.
  54. Khemasuwan D, Chae YK, Gupta S, et al. Dose-related effect of statins in venous thrombosis risk reduction. Am J Med 2011; 124:852.
  55. Nguyen CD, Andersson C, Jensen TB, et al. Statin treatment and risk of recurrent venous thromboembolism: a nationwide cohort study. BMJ Open 2013; 3:e003135.
  56. Li L, Zhang P, Tian JH, Yang K. Statins for primary prevention of venous thromboembolism. Cochrane Database Syst Rev 2014; :CD008203.
  57. Kunutsor SK, Seidu S, Khunti K. Statins and secondary prevention of venous thromboembolism: pooled analysis of published observational cohort studies. Eur Heart J 2017; 38:1608.
  58. Rahimi K, Bhala N, Kamphuisen P, et al. Effect of statins on venous thromboembolic events: a meta-analysis of published and unpublished evidence from randomised controlled trials. PLoS Med 2012; 9:e1001310.
  59. Glynn RJ, Ridker PM, Goldhaber SZ, Buring JE. Effect of low-dose aspirin on the occurrence of venous thromboembolism: a randomized trial. Ann Intern Med 2007; 147:525.
  60. Hull RD, Hirsh J, Sackett DL, Stoddart GL. Cost-effectiveness of primary and secondary prevention of fatal pulmonary embolism in high-risk surgical patients. Can Med Assoc J 1982; 127:990.
  61. Geerts WH, Bergqvist D, Pineo GF, et al. Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008; 133:381S.
  62. Meyer CS, Blebea J, Davis K Jr, et al. Surveillance venous scans for deep venous thrombosis in multiple trauma patients. Ann Vasc Surg 1995; 9:109.
  63. Schellong SM, Beyer J, Kakkar AK, et al. Ultrasound screening for asymptomatic deep vein thrombosis after major orthopaedic surgery: the VENUS study. J Thromb Haemost 2007; 5:1431.
  64. Kahn SR, Lim W, Dunn AS, et al. Prevention of VTE in nonsurgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141:e195S.
  65. Nyquist P, Jichici D, Bautista C, et al. Prophylaxis of Venous Thrombosis in Neurocritical Care Patients: An Executive Summary of Evidence-Based Guidelines: A Statement for Healthcare Professionals From the Neurocritical Care Society and Society of Critical Care Medicine. Crit Care Med 2017; 45:476.
  66. Hill J, Treasure T, National Clinical Guideline Centre for Acute and Chronic Conditions. Reducing the risk of venous thromboembolism in patients admitted to hospital: summary of NICE guidance. BMJ 2010; 340:c95.
  67. Leizorovicz A, Cohen AT, Turpie AG, et al. Randomized, placebo-controlled trial of dalteparin for the prevention of venous thromboembolism in acutely ill medical patients. Circulation 2004; 110:874.
  68. Cohen AT, Davidson BL, Gallus AS, et al. Efficacy and safety of fondaparinux for the prevention of venous thromboembolism in older acute medical patients: randomised placebo controlled trial. BMJ 2006; 332:325.
  69. Alikhan R, Cohen AT. A safety analysis of thromboprophylaxis in acute medical illness. Thromb Haemost 2003; 89:590.
  70. Jois-Bilowich P, Michota F, Bartholomew JR, et al. Venous thromboembolism prophylaxis in hospitalized heart failure patients. J Card Fail 2008; 14:127.
  71. Dentali F, Douketis JD, Gianni M, et al. Meta-analysis: anticoagulant prophylaxis to prevent symptomatic venous thromboembolism in hospitalized medical patients. Ann Intern Med 2007; 146:278.
  72. Wein L, Wein S, Haas SJ, et al. Pharmacological venous thromboembolism prophylaxis in hospitalized medical patients: a meta-analysis of randomized controlled trials. Arch Intern Med 2007; 167:1476.
  73. Själander A, Jansson JH, Bergqvist D, et al. Efficacy and safety of anticoagulant prophylaxis to prevent venous thromboembolism in acutely ill medical inpatients: a meta-analysis. J Intern Med 2008; 263:52.
  74. Lentine KL, Flavin KE, Gould MK. Variability in the use of thromboprophylaxis and outcomes in critically ill medical patients. Am J Med 2005; 118:1373.
  75. Kanaan AO, Silva MA, Donovan JL, et al. Meta-analysis of venous thromboembolism prophylaxis in medically Ill patients. Clin Ther 2007; 29:2395.
  76. Dunn AS, Brenner A, Halm EA. The magnitude of an iatrogenic disorder: a systematic review of the incidence of venous thromboembolism for general medical inpatients. Thromb Haemost 2006; 95:758.
  77. Sherman DG, Albers GW, Bladin C, et al. The efficacy and safety of enoxaparin versus unfractionated heparin for the prevention of venous thromboembolism after acute ischaemic stroke (PREVAIL Study): an open-label randomised comparison. Lancet 2007; 369:1347.
  78. Bergmann JF, Neuhart E. A multicenter randomized double-blind study of enoxaparin compared with unfractionated heparin in the prevention of venous thromboembolic disease in elderly in-patients bedridden for an acute medical illness. The Enoxaparin in Medicine Study Group. Thromb Haemost 1996; 76:529.
  79. Ananthakrishnan AN, Cagan A, Gainer VS, et al. Thromboprophylaxis is associated with reduced post-hospitalization venous thromboembolic events in patients with inflammatory bowel diseases. Clin Gastroenterol Hepatol 2014; 12:1905.
  80. Cohen AT, Spiro TE, Spyropoulos AC, et al. D-dimer as a predictor of venous thromboembolism in acutely ill, hospitalized patients: a subanalysis of the randomized controlled MAGELLAN trial. J Thromb Haemost 2014; 12:479.
  81. Spyropoulos AC, McGinn T, Khorana AA. The use of weighted and scored risk assessment models for venous thromboembolism. Thromb Haemost 2012; 108:1072.
  82. Greene MT, Spyropoulos AC, Chopra V, et al. Validation of Risk Assessment Models of Venous Thromboembolism in Hospitalized Medical Patients. Am J Med 2016; 129:1001.e9.
  83. Kucher N, Koo S, Quiroz R, et al. Electronic alerts to prevent venous thromboembolism among hospitalized patients. N Engl J Med 2005; 352:969.
  84. Barbar S, Noventa F, Rossetto V, et al. A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism: the Padua Prediction Score. J Thromb Haemost 2010; 8:2450.
  85. Nendaz M, Spirk D, Kucher N, et al. Multicentre validation of the Geneva Risk Score for hospitalised medical patients at risk of venous thromboembolism. Explicit ASsessment of Thromboembolic RIsk and Prophylaxis for Medical PATients in SwitzErland (ESTIMATE). Thromb Haemost 2014; 111:531.
  86. Decousus H, Tapson VF, Bergmann JF, et al. Factors at admission associated with bleeding risk in medical patients: findings from the IMPROVE investigators. Chest 2011; 139:69.
  87. Lauzier F, Arnold DM, Rabbat C, et al. Risk factors and impact of major bleeding in critically ill patients receiving heparin thromboprophylaxis. Intensive Care Med 2013; 39:2135.
  88. Sharma A, Chatterjee S, Lichstein E, Mukherjee D. Extended thromboprophylaxis for medically ill patients with decreased mobility: does it improve outcomes? J Thromb Haemost 2012; 10:2053.
  89. Cohen AT, Harrington RA, Goldhaber SZ, et al. Extended Thromboprophylaxis with Betrixaban in Acutely Ill Medical Patients. N Engl J Med 2016; 375:534.
  90. Yusen RD, Hull RD, Schellong SM, et al. Impact of age on the efficacy and safety of extended-duration thromboprophylaxis in medical patients. Subgroup analysis from the EXCLAIM randomised trial. Thromb Haemost 2013; 110:1152.
  91. Goldhaber SZ, Leizorovicz A, Kakkar AK, et al. Apixaban versus enoxaparin for thromboprophylaxis in medically ill patients. N Engl J Med 2011; 365:2167.
  92. Cohen AT, Spiro TE, Büller HR, et al. Rivaroxaban for thromboprophylaxis in acutely ill medical patients. N Engl J Med 2013; 368:513.
  93. Gibson CM, Halaby R, Korjian S, et al. The safety and efficacy of full- versus reduced-dose betrixaban in the Acute Medically Ill VTE (Venous Thromboembolism) Prevention With Extended-Duration Betrixaban (APEX) trial. Am Heart J 2017; 185:93.
  94. Raskob GE, Spyropoulos AC, Zrubek J, et al. The MARINER trial of rivaroxaban after hospital discharge for medical patients at high risk of VTE. Design, rationale, and clinical implications. Thromb Haemost 2016; 115:1240.
  95. Spyropoulos AC, Mahan C. Venous thromboembolism prophylaxis in the medical patient: controversies and perspectives. Am J Med 2009; 122:1077.
  96. Mismetti P, Laporte-Simitsidis S, Tardy B, et al. Prevention of venous thromboembolism in internal medicine with unfractionated or low-molecular-weight heparins: a meta-analysis of randomised clinical trials. Thromb Haemost 2000; 83:14.
  97. Hull RD, Schellong SM, Tapson VF, et al. Late breaking clinical trial: Extended-duration venous thromboembolism (VTE) prophylaxis in acutely ill medical patients with recent mobility: the EXCLAIM study (abstract). J Thromb Haemost 2007; 5(Suppl 1):O.
  98. Bump GM, Dandu M, Kaufman SR, et al. How complete is the evidence for thromboembolism prophylaxis in general medicine patients? A meta-analysis of randomized controlled trials. J Hosp Med 2009; 4:289.
  99. McGarry LJ, Stokes ME, Thompson D. Outcomes of thromboprophylaxis with enoxaparin vs. unfractionated heparin in medical inpatients. Thromb J 2006; 4:17.
  100. Laporte S, Liotier J, Bertoletti L, et al. Individual patient data meta-analysis of enoxaparin vs. unfractionated heparin for venous thromboembolism prevention in medical patients. J Thromb Haemost 2011; 9:464.
  101. Greig MF, Rochow SB, Crilly MA, Mangoni AA. Routine pharmacological venous thromboembolism prophylaxis in frail older hospitalised patients: where is the evidence? Age Ageing 2013; 42:428.
  102. Alikhan R, Bedenis R, Cohen AT. Heparin for the prevention of venous thromboembolism in acutely ill medical patients (excluding stroke and myocardial infarction). Cochrane Database Syst Rev 2014; :CD003747.
  103. Lilly CM, Liu X, Badawi O, et al. Thrombosis prophylaxis and mortality risk among critically ill adults. Chest 2014; 146:51.
  104. Surgical Care Improvement Project (SCIP) http://www.jointcommission.org/surgical_care_improvement_project/ (Accessed on May 02, 2011).
  105. Diener HC, Ringelstein EB, von Kummer R, et al. Prophylaxis of thrombotic and embolic events in acute ischemic stroke with the low-molecular-weight heparin certoparin: results of the PROTECT Trial. Stroke 2006; 37:139.
  106. Shorr AF, Jackson WL, Sherner JH, Moores LK. Differences between low-molecular-weight and unfractionated heparin for venous thromboembolism prevention following ischemic stroke: a metaanalysis. Chest 2008; 133:149.
  107. Alhazzani W, Lim W, Jaeschke RZ, et al. Heparin thromboprophylaxis in medical-surgical critically ill patients: a systematic review and meta-analysis of randomized trials. Crit Care Med 2013; 41:2088.
  108. PROTECT Investigators for the Canadian Critical Care Trials Group and the Australian and New Zealand Intensive Care Society Clinical Trials Group, Cook D, Meade M, et al. Dalteparin versus unfractionated heparin in critically ill patients. N Engl J Med 2011; 364:1305.
  109. Beitland S, Sandven I, Kjærvik LK, et al. Thromboprophylaxis with low molecular weight heparin versus unfractionated heparin in intensive care patients: a systematic review with meta-analysis and trial sequential analysis. Intensive Care Med 2015; 41:1209.
  110. Fowler RA, Mittmann N, Geerts W, et al. Cost-effectiveness of dalteparin vs unfractionated heparin for the prevention of venous thromboembolism in critically ill patients. JAMA 2014; 312:2135.
  111. King CS, Holley AB, Jackson JL, et al. Twice vs three times daily heparin dosing for thromboembolism prophylaxis in the general medical population: A metaanalysis. Chest 2007; 131:507.
  112. Phung OJ, Kahn SR, Cook DJ, Murad MH. Dosing frequency of unfractionated heparin thromboprophylaxis: a meta-analysis. Chest 2011; 140:374.
  113. Warkentin TE, Levine MN, Hirsh J, et al. Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin. N Engl J Med 1995; 332:1330.
  114. Martel N, Lee J, Wells PS. Risk for heparin-induced thrombocytopenia with unfractionated and low-molecular-weight heparin thromboprophylaxis: a meta-analysis. Blood 2005; 106:2710.
  115. Garcia DA, Baglin TP, Weitz JI, et al. Parenteral anticoagulants: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141:e24S.
  116. Ageno W, Riva N, Noris P, et al. Safety and efficacy of low-dose fondaparinux (1.5 mg) for the prevention of venous thromboembolism in acutely ill medical patients with renal impairment: the FONDAIR study. J Thromb Haemost 2012; 10:2291.
  117. Collins R, Baigent C, Sandercock P, Peto R. Antiplatelet therapy for thromboprophylaxis: the need for careful consideration of the evidence from randomised trials. Antiplatelet Trialists' Collaboration. BMJ 1994; 309:1215.
  118. Karthikeyan G, Eikelboom JW, Turpie AG, Hirsh J. Does acetyl salicylic acid (ASA) have a role in the prevention of venous thromboembolism? Br J Haematol 2009; 146:142.
  119. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/208383s000lbl.pdf (Accessed on June 26, 2017).
  120. Roberts VC, Sabri S, Beeley AH, Cotton LT. The effect of intermittently applied external pressure on the haemodynamics of the lower limb in man. Br J Surg 1972; 59:223.
  121. Comerota AJ, Chouhan V, Harada RN, et al. The fibrinolytic effects of intermittent pneumatic compression: mechanism of enhanced fibrinolysis. Ann Surg 1997; 226:306.
  122. CLOTS (Clots in Legs Or sTockings after Stroke) Trials Collaboration, Dennis M, Sandercock P, et al. Effectiveness of intermittent pneumatic compression in reduction of risk of deep vein thrombosis in patients who have had a stroke (CLOTS 3): a multicentre randomised controlled trial. Lancet 2013; 382:516.
  123. André C, de Freitas GR, Fukujima MM. Prevention of deep venous thrombosis and pulmonary embolism following stroke: a systematic review of published articles. Eur J Neurol 2007; 14:21.
  124. CLOTS Trials Collaboration, Dennis M, Sandercock PA, et al. Effectiveness of thigh-length graduated compression stockings to reduce the risk of deep vein thrombosis after stroke (CLOTS trial 1): a multicentre, randomised controlled trial. Lancet 2009; 373:1958.
  125. Pour AE, Keshavarzi NR, Purtill JJ, et al. Is venous foot pump effective in prevention of thromboembolic disease after joint arthroplasty: a meta-analysis. J Arthroplasty 2013; 28:410.
  126. Corley GJ, Broderick BJ, Nestor SM, et al. The anatomy and physiology of the venous foot pump. Anat Rec (Hoboken) 2010; 293:370.
  127. Shojania KG, Duncan BW, McDonald KM, et al. Making health care safer: a critical analysis of patient safety practices. Report/Technology Assessment No. 43. Rockville, MD: Agency for Healthcare Research and Quality. Available at www.ahrq.gov/clinic/pt-safety/. Accessed January 3, 2002.
  128. Specifications Manual for National Hospital Inpatient Quality Measures www.qualitynet.org (Accessed on March 11, 2009).
  129. http://www.qualityforum.org/Projects/s-z/VTE_Phase_I/Venous_Thromboembolism_(VTE)_I.aspx (Accessed on May 02, 2011).
  130. U.S. Department of Health and Human Services and Joint Commission on Accreditation of Health Care Organizations http://www.hhs.gov/ and http://www.jointcommission.org/ (Accessed on May 02, 2011).
  131. Rathbun S. Cardiology patient pages. The Surgeon General's call to action to prevent deep vein thrombosis and pulmonary embolism. Circulation 2009; 119:e480.
  132. Safer Healthcare Now www.saferhealthcarenow.ca (Accessed on May 02, 2011).
  133. National Institute for Health and Clinical Excellence. Reducing the risk of venous thromboembolism (deep vein thrombosis and pulmonary embolism) in patients admitted to hospital. NICE clinical guideline. http://www.nice.org.uk/CG092 (Accessed on June 09, 2010).
  134. Kucher N, Tapson VF, Goldhaber SZ, DVT FREE Steering Committee. Risk factors associated with symptomatic pulmonary embolism in a large cohort of deep vein thrombosis patients. Thromb Haemost 2005; 93:494.
  135. Cohen AT, Tapson VF, Bergmann JF, et al. Venous thromboembolism risk and prophylaxis in the acute hospital care setting (ENDORSE study): a multinational cross-sectional study. Lancet 2008; 371:387.
  136. Kucher N, Leizorovicz A, Vaitkus PT, et al. Efficacy and safety of fixed low-dose dalteparin in preventing venous thromboembolism among obese or elderly hospitalized patients: a subgroup analysis of the PREVENT trial. Arch Intern Med 2005; 165:341.
  137. Rahme E, Dasgupta K, Burman M, et al. Postdischarge thromboprophylaxis and mortality risk after hip-or knee-replacement surgery. CMAJ 2008; 178:1545.
  138. Kahn SR, Panju A, Geerts W, et al. Multicenter evaluation of the use of venous thromboembolism prophylaxis in acutely ill medical patients in Canada. Thromb Res 2007; 119:145.
  139. Tapson VF, Hyers TM, Waldo AL, et al. Antithrombotic therapy practices in US hospitals in an era of practice guidelines. Arch Intern Med 2005; 165:1458.
  140. Cohn SL. Prophylaxis of venous thromboembolism in the US: improving hospital performance. J Thromb Haemost 2009; 7:1437.
  141. Bergmann JF, Cohen AT, Tapson VF, et al. Venous thromboembolism risk and prophylaxis in hospitalised medically ill patients. The ENDORSE Global Survey. Thromb Haemost 2010; 103:736.
  142. Mokhtari M, Salameh P, Kouchek M, et al. The AVAIL ME Extension: a multinational Middle Eastern survey of venous thromboembolism risk and prophylaxis. J Thromb Haemost 2011; 9:1340.
  143. Pendergraft T, Liu X, Edelsberg J, et al. Prophylaxis against venous thromboembolism in hospitalized medically ill patients. Circ Cardiovasc Qual Outcomes 2013; 6:75.
  144. Mahan CE, Spyropoulos AC. Venous thromboembolism prevention: a systematic review of methods to improve prophylaxis and decrease events in the hospitalized patient. Hosp Pract (1995) 2010; 38:97.
  145. Roberts LN, Porter G, Barker RD, et al. Comprehensive VTE prevention program incorporating mandatory risk assessment reduces the incidence of hospital-associated thrombosis. Chest 2013; 144:1276.
  146. Kahn SR, Morrison DR, Cohen JM, et al. Interventions for implementation of thromboprophylaxis in hospitalized medical and surgical patients at risk for venous thromboembolism. Cochrane Database Syst Rev 2013; :CD008201.
  147. Piazza G, Anderson FA, Ortel TL, et al. Randomized trial of physician alerts for thromboprophylaxis after discharge. Am J Med 2013; 126:435.
  148. Mahan CE, Liu Y, Turpie AG, et al. External validation of a risk assessment model for venous thromboembolism in the hospitalised acutely-ill medical patient (VTE-VALOURR). Thromb Haemost 2014; 112:692.
  149. Bagot C, Gohil S, Perrott R, et al. The use of an exclusion-based risk-assessment model for venous thrombosis improves uptake of appropriate thromboprophylaxis in hospitalized medical patients. QJM 2010; 103:597.
  150. Lawall H, Matthiessen A, Hohmann V, et al. Venous thromboembolism in medical outpatients - a cross-sectional survey of risk assessment and prophylaxis. Thromb Haemost 2011; 105:190.
  151. Tooher R, Middleton P, Pham C, et al. A systematic review of strategies to improve prophylaxis for venous thromboembolism in hospitals. Ann Surg 2005; 241:397.
  152. Stinnett JM, Pendleton R, Skordos L, et al. Venous thromboembolism prophylaxis in medically ill patients and the development of strategies to improve prophylaxis rates. Am J Hematol 2005; 78:167.
  153. Schünemann HJ, Cook D, Grimshaw J, et al. Antithrombotic and thrombolytic therapy: from evidence to application: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126:688S.
  154. Yu HT, Dylan ML, Lin J, Dubois RW. Hospitals' compliance with prophylaxis guidelines for venous thromboembolism. Am J Health Syst Pharm 2007; 64:69.
  155. Piazza G, Rosenbaum EJ, Pendergast W, et al. Physician alerts to prevent symptomatic venous thromboembolism in hospitalized patients. Circulation 2009; 119:2196.
  156. Piazza G, Goldhaber SZ. Computerized decision support for the cardiovascular clinician: applications for venous thromboembolism prevention and beyond. Circulation 2009; 120:1133.
  157. Kucher N, Puck M, Blaser J, et al. Physician compliance with advanced electronic alerts for preventing venous thromboembolism among hospitalized medical patients. J Thromb Haemost 2009; 7:1291.
  158. Piazza G, Fanikos J, Zayaruzny M, Goldhaber SZ. Venous thromboembolic events in hospitalised medical patients. Thromb Haemost 2009; 102:505.
  159. Fanikos J, Piazza G, Zayaruzny M, Goldhaber SZ. Long-term complications of medical patients with hospital-acquired venous thromboembolism. Thromb Haemost 2009; 102:688.
  160. Baglin T. Defining the population in need of thromboprophylaxis - making hospitals safer. Br J Haematol 2010; 149:805.