Semin Respir Crit Care Med 2012; 33(02): 163-175
DOI: 10.1055/s-0032-1311795
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Thromboprophylaxis in Surgical and Medical Patients

Silvia Bozzato
1   Department of Clinical Medicine, University of Insubria, Varese, Italy.
,
Luca Galli
1   Department of Clinical Medicine, University of Insubria, Varese, Italy.
,
Walter Ageno
1   Department of Clinical Medicine, University of Insubria, Varese, Italy.
› Author Affiliations
Further Information

Publication History

Publication Date:
30 May 2012 (online)

Abstract

Venous thromboembolism (VTE) remains the most common preventable cause of death in hospitalized patients. There is much evidence to show the efficacy of prophylactic strategies to prevent VTE in at-risk hospitalized patients. For example, pharmacological prophylaxis reduces the risk of pulmonary embolism by 75% in general surgical patients and by 57% in medical patients. Thus international guidelines strongly recommend effective preventive strategies for all hospitalized patients defined as moderate to high risk for VTE. Effective pharmacological thromboprophylaxis includes low-dose unfractionated heparin (UFH), low molecular weight heparin (LMWH), fondaparinux, and warfarin. Mechanical prophylaxis with graduated compression stockings and intermittent pneumatic compression is also recommended as an alternative or in combination with pharmacological prophylaxis. Although the volume of evidence supporting the use of thromboprophylaxis is growing, the number of patients receiving adequate prophylaxis is not. Several studies have shown that nearly half of the patients undergoing major surgery or hospitalized for medical illnesses do not receive appropriate antithrombotic prophylaxis. Reducing the discrepancy between evidence-based recommendations and clinical practice seems to be a cost-effective goal. Developing and promoting local protocols and educational activities to encourage prophylaxis in daily clinical practice may be effective. New oral anticoagulant drugs with potentially favorable pharmacokinetic and pharmacodynamic characteristics have been developed. After the positive results of phase 3 clinical trials, some of these drugs have been approved for clinical use in the prevention of VTE in the high-risk setting of major orthopedic surgery. These agents include the direct thrombin inhibitor dabigatran etexilate and the direct factor Xa inhibitors rivaroxaban and apixaban.

 
  • References

  • 1 Anderson Jr FA, Wheeler HB, Goldberg RJ , et al. A population-based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism. The Worcester DVT Study. Arch Intern Med 1991; 151 (5) 933-938
  • 2 Geerts WH, Pineo GF, Heit JA , et al. Prevention of venous thromboembolism: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest 2004; 126 (3 Suppl) 338S-400S
  • 3 Lindblad B, Sternby NH, Bergqvist D. Incidence of venous thromboembolism verified by necroscopy over 30 years. BMJ 1991; 302 (6778) 709-711
  • 4 Sandler DA, Martin JF. Autopsy proven pulmonary embolism in hospital patients: are we detecting enough deep vein thrombosis?. J R Soc Med 1989; 82 (4) 203-205
  • 5 Alikhan R, Peters F, Wilmott R, Cohen AT. Fatal pulmonary embolism in hospitalised patients: a necropsy review. J Clin Pathol 2004; 57 (12) 1254-1257
  • 6 Otero R, Uresandi F, Cayuela A , et al. Use of venous thromboembolism prophylaxis for surgical patients: a multicentre analysis of practice in Spain. Eur J Surg 2001; 167 (3) 163-167
  • 7 Yu HT, Dylan ML, Lin J, Dubois RW. Hospitals' compliance with prophylaxis guidelines for venous thromboembolism. Am J Health Syst Pharm 2007; 64 (1) 69-76
  • 8 Cohen AT, Tapson VF, Bergmann JF , et al; ENDORSE Investigators. Venous thromboembolism risk and prophylaxis in the acute hospital care setting (ENDORSE study): a multinational cross-sectional study. Lancet 2008; 371 (9610) 387-394
  • 9 Stratton MA, Anderson FA, Bussey HI , et al. Prevention of venous thromboembolism: adherence to the 1995 American College of Chest Physicians consensus guidelines for surgical patients. Arch Intern Med 2000; 160 (3) 334-340
  • 10 Tapson VF, Decousus H, Pini M , et al; IMPROVE Investigators. Venous thromboembolism prophylaxis in acutely ill hospitalized medical patients: findings from the International Medical Prevention Registry on Venous Thromboembolism. Chest 2007; 132 (3) 936-945
  • 11 Kahn SR, Panju A, Geerts W , et al; CURVE study investigators. Multicenter evaluation of the use of venous thromboembolism prophylaxis in acutely ill medical patients in Canada. Thromb Res 2007; 119 (2) 145-155
  • 12 Cohen AT, Agnelli G, Anderson FA , et al; VTE Impact Assessment Group in Europe (VITAE). Venous thromboembolism (VTE) in Europe: the number of VTE events and associated morbidity and mortality. Thromb Haemost 2007; 98 (4) 756-764
  • 13 Ageno W, Dentali F. Prevention of in-hospital VTE: why can't we do better?. Lancet 2008; 371 (9610) 361-362
  • 14 Samama MM, Cohen AT, Darmon JY , et al; Prophylaxis in Medical Patients with Enoxaparin Study Group. A comparison of enoxaparin with placebo for the prevention of venous thromboembolism in acutely ill medical patients. N Engl J Med 1999; 341 (11) 793-800
  • 15 Leizorovicz A, Cohen AT, Turpie AG, Olsson CG, Vaitkus PT, Goldhaber SZ. ; PREVENT Medical Thromboprophylaxis Study Group. Randomized, placebo-controlled trial of dalteparin for the prevention of venous thromboembolism in acutely ill medical patients. Circulation 2004; 110 (7) 874-879
  • 16 Geerts WH, Bergqvist D, Pineo GF , et al; American College of Chest Physicians. Prevention of venous thromboembolism: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th edition). Chest 2008; 133 (6, Suppl) 381S-453S
  • 17 Gangireddy C, Rectenwald JR, Upchurch GR , et al. Risk factors and clinical impact of postoperative symptomatic venous thromboembolism. J Vasc Surg 2007; 45 (2) 335-341 , discussion 341–342
  • 18 Turpie AG, Bauer KA, Caprini JA, Comp PC, Gent M, Muntz JE. ; Apollo Investigators. Fondaparinux combined with intermittent pneumatic compression vs. intermittent pneumatic compression alone for prevention of venous thromboembolism after abdominal surgery: a randomized, double-blind comparison. J Thromb Haemost 2007; 5 (9) 1854-1861
  • 19 Agnelli G, Bolis G, Capussotti L , et al. A clinical outcome-based prospective study on venous thromboembolism after cancer surgery: the @RISTOS project. Ann Surg 2006; 243 (1) 89-95
  • 20 Hendolin H, Mattila MA, Poikolainen E. The effect of lumbar epidural analgesia on the development of deep vein thrombosis of the legs after open prostatectomy. Acta Chir Scand 1981; 147 (6) 425-429
  • 21 International Multicenter Trial. Prevention of fatal postoperative pulmonary embolism by low doses of heparin. An international multicentre trial. Lancet 1975; 2 (7924) 45-51
  • 22 Clagett GP, Reisch JS. Prevention of venous thromboembolism in general surgical patients: results of meta-analysis. Ann Surg 1988; 208 (2) 227-240
  • 23 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 (18) 1162-1173
  • 24 Mismetti P, Laporte S, Darmon JY, Buchmüller A, Decousus H. Meta-analysis of low molecular weight heparin in the prevention of venous thromboembolism in general surgery. Br J Surg 2001; 88 (7) 913-930
  • 25 Agnelli G, Bergqvist D, Cohen AT, Gallus AS, Gent M. ; PEGASUS investigators. Randomized clinical trial of postoperative fondaparinux versus perioperative dalteparin for prevention of venous thromboembolism in high-risk abdominal surgery. Br J Surg 2005; 92 (10) 1212-1220
  • 26 Gallus AS. Prevention of post-operative deep leg vein thrombosis in patients with cancer. Thromb Haemost 1997; 78 (1) 126-132
  • 27 Kakkar AK, Williamson RC. Prevention of venous thromboembolism in cancer patients. Semin Thromb Hemost 1999; 25 (2) 239-243
  • 28 Bergqvist D. Venous thromboembolism and cancer: prevention of VTE. Thromb Res 2001; 102 (6) V209-V213
  • 29 Kakkar AK, Haas S, Wolf H, Encke A. Evaluation of perioperative fatal pulmonary embolism and death in cancer surgical patients: the MC-4 cancer substudy. Thromb Haemost 2005; 94 (4) 867-871
  • 30 Agnelli G, Bolis G, Capussotti L , et al. A clinical outcome-based prospective study on venous thromboembolism after cancer surgery: the @RISTOS project. Ann Surg 2006; 243 (1) 89-95
  • 31 Bergqvist D, Agnelli G, Cohen AT , et al; ENOXACAN II Investigators. Duration of prophylaxis against venous thromboembolism with enoxaparin after surgery for cancer. N Engl J Med 2002; 346 (13) 975-980
  • 32 Rasmussen MS, Jorgensen LN, Wille-Jørgensen P , et al; FAME Investigators. Prolonged prophylaxis with dalteparin to prevent late thromboembolic complications in patients undergoing major abdominal surgery: a multicenter randomized open-label study. J Thromb Haemost 2006; 4 (11) 2384-2390
  • 33 Kearon C. Natural history of venous thromboembolism. Circulation 2003; 107 (23, Suppl 1) I22-I30
  • 34 Mismetti P, Laporte S, Zufferey P, Epinat M, Decousus H, Cucherat M. Prevention of venous thromboembolism in orthopedic surgery with vitamin K antagonists: a meta-analysis. J Thromb Haemost 2004; 2 (7) 1058-1070
  • 35 Turpie AG, Bauer KA, Eriksson BI, Lassen MR. Fondaparinux vs enoxaparin for the prevention of venous thromboembolism in major orthopedic surgery: a meta-analysis of 4 randomized double-blind studies. Arch Intern Med 2002; 162 (16) 1833-1840
  • 36 Hull RD, Pineo GF, Stein PD , et al. Extended out-of-hospital low-molecular-weight heparin prophylaxis against deep venous thrombosis in patients after elective hip arthroplasty: a systematic review. Ann Intern Med 2001; 135 (10) 858-869
  • 37 Eriksson BI, Lassen MR. ; PENTasaccharide in HIp-FRActure Surgery Plus Investigators. Duration of prophylaxis against venous thromboembolism with fondaparinux after hip fracture surgery: a multicenter, randomized, placebo-controlled, double-blind study. Arch Intern Med 2003; 163 (11) 1337-1342
  • 38 Ettema HB, Hoppener MR, Veeger NJ, Büller HR, van der Meer J. Low incidence of venographically detected deep vein thrombosis after knee arthroscopy without thromboprophylaxis: a prospective cohort study. J Thromb Haemost 2006; 4 (6) 1411-1413
  • 39 Hoppener MR, Ettema HB, Henny CP, Verheyen CC, Büller HR. Low incidence of deep vein thrombosis after knee arthroscopy without thromboprophylaxis: a prospective cohort study of 335 patients. Acta Orthop 2006; 77 (5) 767-771
  • 40 Wirth T, Schneider B, Misselwitz F , et al. Prevention of venous thromboembolism after knee arthroscopy with low-molecular weight heparin (reviparin): results of a randomized controlled trial. Arthroscopy 2001; 17 (4) 393-399
  • 41 Michot M, Conen D, Holtz D , et al. Prevention of deep-vein thrombosis in ambulatory arthroscopic knee surgery: a randomized trial of prophylaxis with low-molecular-weight heparin. Arthroscopy 2002; 18 (3) 257-263
  • 42 Camporese G, Bernardi E, Prandoni P , et al; KANT (Knee Arthroscopy Nadroparin Thromboprophylaxis) Study Group. Low-molecular-weight heparin versus compression stockings for thromboprophylaxis after knee arthroscopy: a randomized trial. Ann Intern Med 2008; 149 (2) 73-82
  • 43 Geerts WH, Heit JA, Clagett GP , et al. Prevention of venous thromboembolism. Chest 2001; 119 (1, Suppl) 132S-175S
  • 44 Collen JF, Jackson JL, Shorr AF, Moores LK. Prevention of venous thromboembolism in neurosurgery: a metaanalysis. Chest 2008; 134 (2) 237-249
  • 45 Turner JA, Ersek M, Herron L , et al. Patient outcomes after lumbar spinal fusions. JAMA 1992; 268 (7) 907-911
  • 46 Oda T, Fuji T, Kato Y, Fujita S, Kanemitsu N. Deep venous thrombosis after posterior spinal surgery. Spine 2000; 25 (22) 2962-2967
  • 47 Goldhaber SZ, Tapson VF. ; DVT FREE Steering Committee. A prospective registry of 5,451 patients with ultrasound-confirmed deep vein thrombosis. Am J Cardiol 2004; 93 (2) 259-262
  • 48 Sandler DA, Martin JF. Autopsy proven pulmonary embolism in hospital patients: are we detecting enough deep vein thrombosis?. J R Soc Med 1989; 82 (4) 203-205
  • 49 Heit JA, Silverstein MD, Mohr DN, Petterson TM, O'Fallon WM, Melton III LJ. Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case-control study. Arch Intern Med 2000; 160 (6) 809-815
  • 50 Vaitkus PT, Leizorovicz A, Cohen AT, Turpie AG, Olsson CG, Goldhaber SZ. ; PREVENT Medical Thromboprophylaxis Study Group. Mortality rates and risk factors for asymptomatic deep vein thrombosis in medical patients. Thromb Haemost 2005; 93 (1) 76-79
  • 51 Alikhan R, Cohen AT, Combe S , et al; MEDENOX Study. Risk factors for venous thromboembolism in hospitalized patients with acute medical illness: analysis of the MEDENOX Study. Arch Intern Med 2004; 164 (9) 963-968
  • 52 Dentali F, Douketis JD, Gianni M, Lim W, Crowther MA. Meta-analysis: anticoagulant prophylaxis to prevent symptomatic venous thromboembolism in hospitalized medical patients. Ann Intern Med 2007; 146 (4) 278-288
  • 53 Kanaan AO, Silva MA, Donovan JL, Roy T, Al-Homsi AS. Meta-analysis of venous thromboembolism prophylaxis in medically Ill patients. Clin Ther 2007; 29 (11) 2395-2405
  • 54 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 (8) 2710-2715
  • 55 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 (7537) 325-329
  • 56 Hull RD, Schellong SM, Tapson VF , et al; EXCLAIM (Extended Prophylaxis for Venous ThromboEmbolism in Acutely Ill Medical Patients With Prolonged Immobilization) study. Extended-duration venous thromboembolism prophylaxis in acutely ill medical patients with recently reduced mobility: a randomized trial. Ann Intern Med 2010; 153 (1) 8-18
  • 57 Blom JW, Doggen CJ, Osanto S, Rosendaal FR. Malignancies, prothrombotic mutations, and the risk of venous thrombosis. JAMA 2005; 293 (6) 715-722
  • 58 Arkel YS. Thrombosis and cancer. Semin Oncol 2000; 27 (3) 362-374
  • 59 Elting LS, Escalante CP, Cooksley C , et al. Outcomes and cost of deep venous thrombosis among patients with cancer. Arch Intern Med 2004; 164 (15) 1653-1661
  • 60 Blom JW, Vanderschoot JP, Oostindiër MJ, Osanto S, van der Meer FJ, Rosendaal FR. Incidence of venous thrombosis in a large cohort of 66,329 cancer patients: results of a record linkage study. J Thromb Haemost 2006; 4 (3) 529-535
  • 61 Prandoni P, Lensing AW, Piccioli A , et al. Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood 2002; 100 (10) 3484-3488
  • 62 Descourt R, Le Gal G, Couturaud F , et al. Recurrent venous thromboembolism under anticoagulant therapy: a high risk in adenocarcinoma?. Thromb Haemost 2006; 95 (5) 912-913
  • 63 Sørensen HT, Mellemkjaer L, Olsen JH, Baron JA. Prognosis of cancers associated with venous thromboembolism. N Engl J Med 2000; 343 (25) 1846-1850
  • 64 Alcalay A, Wun T, Khatri V , et al. Venous thromboembolism in patients with colorectal cancer: incidence and effect on survival. J Clin Oncol 2006; 24 (7) 1112-1118
  • 65 Chew HK, Wun T, Harvey D, Zhou H, White RH. Incidence of venous thromboembolism and its effect on survival among patients with common cancers. Arch Intern Med 2006; 166 (4) 458-464
  • 66 Khorana AA, Francis CW, Culakova E, Kuderer NM, Lyman GH. Frequency, risk factors, and trends for venous thromboembolism among hospitalized cancer patients. Cancer 2007; 110 (10) 2339-2346
  • 67 Lyman GH, Khorana AA, Falanga A , et al; American Society of Clinical Oncology. American Society of Clinical Oncology guideline: recommendations for venous thromboembolism prophylaxis and treatment in patients with cancer. J Clin Oncol 2007; 25 (34) 5490-5505
  • 68 Lee AY, Levine MN. Venous thromboembolism and cancer: risks and outcomes. Circulation 2003; 107 (23, Suppl 1) I17-I21
  • 69 Fisher B, Costantino JP, Wickerham DL , et al. Tamoxifen for the prevention of breast cancer: current status of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst 2005; 97 (22) 1652-1662
  • 70 Bohlius J, Wilson J, Seidenfeld J , et al. Recombinant human erythropoietins and cancer patients: updated meta-analysis of 57 studies including 9353 patients. J Natl Cancer Inst 2006; 98 (10) 708-714
  • 71 Khorana AA, Francis CW, Blumberg N, Culakova E, Refaai MA, Lyman GH. Blood transfusions, thrombosis, and mortality in hospitalized patients with cancer. Arch Intern Med 2008; 168 (21) 2377-2381
  • 72 Bern MM, Lokich JJ, Wallach SR , et al. Very low doses of warfarin can prevent thrombosis in central venous catheters: a randomized prospective trial. Ann Intern Med 1990; 112 (6) 423-428
  • 73 Randolph AG, Cook DJ, Gonzales CA, Andrew M. Benefit of heparin in central venous and pulmonary artery catheters: a meta-analysis of randomized controlled trials. Chest 1998; 113 (1) 165-171
  • 74 Akl EA, van Doormaal FF, Barba M , et al. Parenteral anticoagulation for prolonging survival in patients with cancer who have no other indication for anticoagulation. Cochrane Database Syst Rev 2007; (3) CD006652
  • 75 Weitz JI, Hirsh J, Samama MM. ; American College of Chest Physicians. New antithrombotic drugs: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th edition). Chest 2008; 133 (6, Suppl) 234S-256S
  • 76 Eriksson BI, Borris LC, Friedman RJ , et al; RECORD1 Study Group. Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med 2008; 358 (26) 2765-2775
  • 77 Kakkar AK, Brenner B, Dahl OE , et al; RECORD2 Investigators. Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after total hip arthroplasty: a double-blind, randomised controlled trial. Lancet 2008; 372 (9632) 31-39
  • 78 Lassen MR, Ageno W, Borris LC , et al; RECORD3 Investigators. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. N Engl J Med 2008; 358 (26) 2776-2786
  • 79 Turpie AG, Lassen MR, Davidson BL , et al; RECORD4 Investigators. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised trial. Lancet 2009; 373 (9676) 1673-1680
  • 80 Turpie AG, Lassen MR, Eriksson BI , et al. Rivaroxaban for the prevention of venous thromboembolism after hip or knee arthroplasty: pooled analysis of four studies. Thromb Haemost 2011; 105 (3) 444-453
  • 81 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 (6) 594-604
  • 82 Lassen MR, Raskob GE, Gallus AS, 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 (9717) 807-815
  • 83 Lassen MR, Gallus A, Raskob GE , et al. Apixaban versus enoxaparin for thromboprophylaxis after hip replacement. N Engl J Med 2010; 363 (26) 2487-2498
  • 84 Raskob G, Cohen AT, Eriksson BI , et al. Oral direct factor Xa inhibition with edoxaban for thromboprophylaxis after elective total hip replacement. A randomised double-blind dose-response study. Thromb Haemost 2010; 104 (3) 642-649
  • 85 Weitz JI, Cao C, Eriksson BI , et al. A dose-finding study with TAK-442, an oral factor Xa inhibitor, in patients undergoing elective total knee replacement surgery. Thromb Haemost 2010; 104 (6) 1150-1157
  • 86 Turpie AG, Bauer KA, Davidson BL , et al; EXPERT Study Group. A randomized evaluation of betrixaban, an oral factor Xa inhibitor, for prevention of thromboembolic events after total knee replacement (EXPERT). Thromb Haemost 2009; 101 (1) 68-76
  • 87 Eriksson BI, Turpie AG, Lassen MR , et al; ONYX-2 STUDY GROUP. Prevention of venous thromboembolism with an oral factor Xa inhibitor, YM150, after total hip arthroplasty: a dose finding study (ONYX-2). J Thromb Haemost 2010; 8 (4) 714-721
  • 88 Agnelli G, Haas S, Ginsberg JS, Krueger KA, Dmitrienko A, Brandt JT. A phase II study of the oral factor Xa inhibitor LY517717 for the prevention of venous thromboembolism after hip or knee replacement. J Thromb Haemost 2007; 5 (4) 746-753
  • 89 European Medicines Agency (EMEA) European public assessment report: Pradaxa. http://www.emea.europa.eu . Accessed June 2011
  • 90 Eriksson BI, Dahl OE, Rosencher N , et al; RE-NOVATE Study Group. Dabigatran etexilate versus enoxaparin for prevention of venous thromboembolism after total hip replacement: a randomised, double-blind, non-inferiority trial. Lancet 2007; 370 (9591) 949-956
  • 91 Eriksson BI, Dahl OE, Rosencher N , et al; RE-MODEL Study Group. Oral dabigatran etexilate vs. subcutaneous enoxaparin for the prevention of venous thromboembolism after total knee replacement: the RE-MODEL randomized trial. J Thromb Haemost 2007; 5 (11) 2178-2185
  • 92 Ginsberg JS, Davidson BL, Comp PC , et al; RE-MOBILIZE Writing Committee. Oral thrombin inhibitor dabigatran etexilate vs North American enoxaparin regimen for prevention of venous thromboembolism after knee arthroplasty surgery. J Arthroplasty 2009; 24 (1) 1-9
  • 93 Friedman RJ, Dahl OE, Rosencher N , et al; RE-MOBILIZE, RE-MODEL, RE-NOVATE Steering Committees. Dabigatran versus enoxaparin for prevention of venous thromboembolism after hip or knee arthroplasty: a pooled analysis of three trials. Thromb Res 2010; 126 (3) 175-182