Semin Respir Crit Care Med 2008; 29(1): 075-082
DOI: 10.1055/s-2008-1047565
© Thieme Medical Publishers

Venous Thromboembolism Prophylaxis for the Medical Patient: Where Do We Stand?

Yshai Yavin1 , Alexander T. Cohen1
  • 1Vascular Medicine, Department of Vascular Surgery, King's College Hospital, London, United Kingdom
Further Information

Publication History

Publication Date:
26 March 2008 (online)

ABSTRACT

Acutely ill medical patients are at moderate to high risk of venous thromboembolism: ~10 to 30% of general medical patients may develop deep vein thrombosis or pulmonary embolism, and the latter is a leading contributor to deaths in hospital. Medical conditions associated with a high risk of venous thromboembolism include cardiac disease, cancer, respiratory disease, inflammatory bowel disease, and infectious diseases. Predisposing risk factors in medical patients include a history of venous thromboembolism, history of malignancy, complicating infections, increasing age, thrombophilia, prolonged immobility, and obesity. Heparins, including unfractionated and low molecular weight, as well as fondaparinux have been shown to be effective agents in prevention of VTE in this setting. However, it has not yet been possible to demonstrate a significant effect on mortality rates in this population. In medical patients, unfractionated heparin has a higher rate of bleeding complications than low molecular weight heparin. There is no evidence for the use of aspirin, warfarin, or mechanical methods. We recommend either low molecular weight heparin or fondaparinux as safe and effective agents in the thromboprophylaxis of medical patients.

REFERENCES

  • 1 Lindblad B, Sternby N H, Bergqvist D. Incidence of venous thromboembolism verified by necropsy over 30 years.  BMJ. 1991;  302 709-711
  • 2 Sandler D A, Martin J F. Autopsy proven pulmonary embolism in hospital patients: are we detecting enough deep vein thrombosis?.  J R Soc Med. 1989;  82 203-205
  • 3 Cohen A T, Edmondson R A, Phillips M J, Ward V P, Kakkar V V. The changing pattern of venous thromboembolic disease.  Haemostasis. 1996;  26 65-71
  • 4 Geerts W H, Pineo G F, Heit J A et al.. Prevention of venous thromboembolism: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy.  Chest. 2004;  126 338S-400S
  • 5 Sperry K L, Key C R, Anderson R E. Toward a population-based assessment of death due to pulmonary embolism in New Mexico.  Hum Pathol. 1990;  21 159-165
  • 6 Shojania K G, Duncan B W, McDonald K M et al.. Making health care safer: a critical analysis of patient safety practices. Evidence Report/Technology Assessment No. 43 (Prepared by the University of California at San Francisco Stanford Evidence-Based Practice Center under Contract No. 290-97-0013). Rockville, MD; Agency for Healthcare Research and Quality July 2001: 332-346 AHRQ Publication No. 01-E058 http://Available at www.ahrq.gov/clinic/pt-safety/ Accessed January 3, 2002
  • 7 Samama M M, Cohen A T, Darmon J-Y et al.. A comparison of enoxaparin with placebo for the prevention of venous thromboembolism in acutely ill medical patients.  N Engl J Med. 1999;  341 793-800
  • 8 Leizorovicz A, Cohen A T, Turpie A GG, Olsson C G, Vaitkus P T, Goldhaber S Z. A randomized placebo controlled trial of dalteparin for the prevention of venous thromboembolism in acutely ill medical patients.  Circulation. 2004;  110 874-879
  • 9 Nicolaides A N, Breddin H K, Fareed J et al.. Prevention of venous thromboembolism. International Consensus Statement Guidelines compiled in accordance with the scientific evidence.  Int Angiol. 2001;  20 1-37
  • 10 Anderson F A, Wheeler H B, Goldberg R J, Hosmer D W, Forcier A, Patwardhan N A. Physician practices in the prevention of venous thromboembolism.  Ann Intern Med. 1991;  115 591-595
  • 11 Ageno W, Squizzata A, Ambrosini F et al.. Thrombosis prophylaxis in medical patients: a retrospective review of clinical practice patterns.  Haematologica. 2002;  87 746-750
  • 12 Ahmad H A, Geissler A, Maclellan D G. Deep venous thrombosis prophylaxis: are guidelines being followed?.  ANZ J Surg. 2002;  72 331-334
  • 13 Bergmann J-F, Mouly S. Thromboprophylaxis in medical patients: focus on France.  Semin Thromb Hemost. 2002;  28(Suppl 3) 51-55
  • 14 Arcelus J I, Candocia S, Traverso C I, Fabrega F, Caprini J A, Hasty J H. Venous thromboembolism prophylaxis and risk assessment in medical patients.  Semin Thromb Hemost. 1991;  17(Suppl 3) 313-318
  • 15 Geerts W H, Heit J A, Clagett G P et al.. Prevention of venous thromboembolism.  Chest. 2001;  119 132S-175S
  • 16 Emerson P A, Marks P. Preventing thromboembolism after myocardial infarction: effect of low-dose heparin or smoking.  BMJ. 1977;  1 18-20
  • 17 Handley A J. Low-dose heparin after myocardial infarction.  Lancet. 1972;  2 623-624
  • 18 Warlow C, Beattie A G, Terry G, Ogston D, Kenmure A CF, Douglas A S. A double-blind trial of low doses of subcutaneous heparin in the prevention of deep-vein thrombosis after myocardial infarction.  Lancet. 1973;  2 934-936
  • 19 Belch J J, Lowe G DO, Ward A G, Forbes C D, Prentice C RM. Prevention of deep vein thrombosis in medical patients by low-dose heparin.  Scott Med J. 1981;  26 115-117
  • 20 Anderson G M, Hull E. The effect of dicumarol upon the mortality and incidence of thromboembolic complications in congestive heart failure.  Am Heart J. 1950;  39 697-702
  • 21 Kierkegaard A, Norgren L, Olsson C-G, Castenfors J, Persson G, Persson S. Incidence of deep vein thrombosis in bedridden non-surgical patients.  Acta Med Scand. 1987;  222 409-414
  • 22 Donati M B. Cancer and thrombosis.  Haemostasis. 1994;  24 128-131
  • 23 Falanga A, Donati M B. Pathogenesis of thrombosis in patients with malignancy.  Int J Hematol. 2001;  73 137-144
  • 24 Sutherland D E, Weitz I C, Liebman H A. Thromboembolic complications of cancer: epidemiology, pathogenesis, diagnosis, and treatment.  Am J Hematol. 2003;  72 43-52
  • 25 Otten H MMB, Prins M H, Smorenburg S M, Hutten B A. Risk assessment and prophylaxis of venous thromboembolism in non-surgical patients: cancer as a risk factor.  Haemostasis. 2000;  30(Suppl 2) 72-76
  • 26 Clarke-Pearson D L, Synan I S, Colemen R E, Hinshaw W, Creasman W T. The natural history of postoperative venous thromboemboli in gynaecologic oncology: a prospective study of 382 patients.  Am J Obstet Gynecol. 1984;  148 1051-1054
  • 27 Marras L C, Geerts W H, Perry J R. The risk of venous thromboembolism is increased throughout the course of malignant glioma: an evidence-based review.  Cancer. 2000;  89 640-646
  • 28 Fraisse F, Holzapfel L, Coulaud J-M et al.. Nadroparin in the prevention of deep vein thrombosis in acute decompensated COPD.  Am J Respir Crit Care Med. 2000;  161 1109-1114
  • 29 Prescott S M, Richards K L, Tikoff G, Armstrong Jr J D, Shigeoka J W. Venous thromboembolism in decompensated chronic obstructive pulmonary disease: a prospective study.  Am Rev Respir Dis. 1981;  123 32-36
  • 30 Miehsler W, Reinisch W, Valic E et al.. Is inflammatory bowel disease an independent and disease specific risk factor for thromboembolism?.  Gut. 2004;  53 542-548
  • 31 Haas S K. Venous thromboembolic risk and its prevention in hospitalized medical patients.  Semin Thromb Hemost. 2002;  28 577-584
  • 32 Motykie G D, Caprini J A, Arcelus J I et al.. Risk factor assessment in the management of patients with suspected deep vein thrombosis.  Int Angiol. 2000;  19 47-51
  • 33 Alikhan R, Cohen A T, Combe S et al.. Prevention of venous thromboembolism in medical patients with enoxaparin: a subgroup analysis of the MEDENOX Study.  Blood Coagul Fibrinolysis. 2003;  14 341-346
  • 34 Sandercock P AG, van den Belt A GM, Lindley R I, Slattery J. Antithrombotic therapy in acute ischaemic stroke: an overview of the completed randomised trials.  J Neurol Neurosurg Psychiatry. 1993;  56 17-25
  • 35 Levine M N, Raskob G, Landefeld S, Kearon C. Hemorrhagic complications of anticoagulant treatment.  Chest. 2001;  119(Suppl) 108S-121S
  • 36 Alikhan R, Cohen A T, Combe S et al.. Risk factors for venous thromboembolism in hospitalized patients with acute medical illness: analysis of the MEDENOX Study.  Arch Intern Med. 2004;  164 963-968
  • 37 Smeeth L, Cook C, Thomas S et al.. Risk of deep vein thrombosis and pulmonary embolism after acute infection in a community setting.  Lancet. 2006;  367 1075-1080
  • 38 Samama M-M. An epidemiologic study of risk factors for deep vein thrombosis in medical outpatients.  Arch Intern Med. 2000;  160 3415-3420
  • 39 Heit J A, Silverstein M D, Mohr D N et al.. The epidemiology of venous thromboembolism in the community.  Thromb Haemost. 2001;  86 452-463
  • 40 Bauer K A. The thrombophilias: well-defined risk factors with uncertain therapeutic implications.  Ann Intern Med. 2001;  135 367-373
  • 41 Laffan M, Tuddenham E. Assessing thrombotic risk.  BMJ. 1998;  317 520-523
  • 42 Gensini G F, Prisco D, Falciani M, Comeglio M, Colella A. Identification of candidates for prevention of venous thromboembolism.  Semin Thromb Hemost. 1997;  23 55-67
  • 43 Abdollahi M, Cushman M, Rosendaal F R. Obesity: risk of venous thrombosis and the interaction with coagulation factor levels and oral contraceptive use.  Thromb Haemost. 2003;  89 493-498
  • 44 Goldhaber S Z, Grodstein F, Stampfer M J et al.. A prospective study of risk factors for pulmonary embolism in women.  JAMA. 1997;  277 642-645
  • 45 Cohen A T, Davidson B L, Gallus A S et al.. Efficacy and safety of fondaparinux for the prevention of VTE in older acute medical patients.  BMJ. 2006;  332 325-329
  • 46 Leone G, Sica S, Chiusolo P, Teofili L, de Stefano V. Blood cell diseases and thrombosis.  Haematologica. 2001;  86 1236-1244
  • 47 Daly E, Vessey M P, Hawkins M M, Carson J L, Gough P, Marsh S. Risk of venous thromboembolism in users of hormone replacement therapy.  Lancet. 1996;  348 977-980
  • 48 Daly E, Vessey M P, Painter R, Hawkins M M. Case-control study of venous thromboembolism in users of hormone replacement therapy.  Lancet. 1996;  348 1027
  • 49 Grady D, Wenger N K, Herrington D et al.. Postmenopausal hormone replacement therapy increases risk for venous thromboembolic disease. The Heart and Estrogen/progestin Replacement Study.  Ann Intern Med. 2000;  132 689-696
  • 50 Hulley S, Furberg C, Barrett-Connor E et al.. Noncardiovascular disease outcomes during 6.8 years of hormone therapy. Heart and Estrogen/progestin Replacement Study follow-up (HERS II).  JAMA. 2002;  288 58-66
  • 51 Bates S M. Treatment and prophylaxis of venous thromboembolism during pregnancy.  Thromb Res. 2002;  108 97-106
  • 52 Kakkar V V, Corrigan T P, Fossard D P. Prevention of fatal postoperative pulmonary embolism by low doses of heparin: reappraisal of results of international multicentre trial.  Lancet. 1977;  1 567-569
  • 53 Carter C J, Kelton J G, Hirsh J et al.. The relationship between haemorrhagic and antithrombotic properties of low molecular weight heparin in rabbits.  Blood. 1982;  59 1239-1245
  • 54 Esquivel C O, Bergqvist D, Bjork C G, Nilsson B. Comparison between commercial heparin, low molecular weight heparin and pentosan polysulfate on hemostasis and platelets in vivo.  Thromb Res. 1982;  28 389-399
  • 55 Cade J F. High risk of the critically ill for venous thromboembolism.  Crit Care Med. 1982;  10 448-450
  • 56 Cade J F, Andrews J T, Stubbs A E. Comparison of sodium and calcium heparin in prevention of venous thromboembolism.  Aust N Z J Med. 1982;  12 501-504
  • 57 Ibarra-Pérez C, Lau-Cortés E, Colmenero-Zubiate S et al.. Prevalence and prevention of deep vein thrombosis of the lower extremities in high-risk pulmonary patients.  Angiology. 1988;  39 505-513
  • 58 Gårdlund B. Randomised, controlled trial of low-dose heparin for prevention of fatal pulmonary embolism in patients with infectious diseases.  Lancet. 1996;  347 1357-1361
  • 59 Mismetti P, Laporte-Simitsidis S, Tardy B et al.. Prevention of venous thromboembolism in internal medicine with unfractionated heparin or low-molecular-weight heparins: a meta-analysis of randomised clinical trials.  Thromb Haemost. 2000;  83 14-19
  • 60 Mahe I, Bergmann J F, d'Azemar P, Vaissie J J, Caulin C. Lack of effect of a low-molecular-weight heparin (nadroparin) on mortality in bedridden medical in-patients: a prospective randomized double-blind study.  Eur J Clin Pharmacol. 2005;  61 347-351
  • 61 Dentali F, Douketis J D, Gianni M, Lim W, Crowther M A. Meta-analysis: anticoagulant prophylaxis to prevent symptomatic venous thromboembolism in hospitalized medical patients.  Ann Intern Med. 2007;  146 278-288
  • 62 Lechler E, Schramm W, Flosbach C W. for THE PRIME Study Group . The venous thrombotic risk in non-surgical patients: epidemiological data and efficacy/safety profile of a low-molecular-weight heparin (enoxaparin).  Haemostasis. 1996;  26(Suppl 2) 49-56
  • 63 Kleber F-X, Witt C, Vogel G, Koppenhagen K, Schomaker U, Flosbach C W. for THE PRINCE Study Group . A randomized comparison of enoxaparin with unfractionated heparin for the prevention of venous thromboembolism in medical patients with heart failure or severe respiratory disease.  Am Heart J. 2003;  145 614-621
  • 64 Hillbom M, Erilä T, Sotaniemi K, Tatlisumak T, Sarna S, Kaste M. Enoxaparin vs heparin for prevention of deep vein thrombosis in acute ischaemic stroke: a randomized, double-blind study.  Acta Neurol Scand. 2002;  106 84-92
  • 65 Antiplatelet Trialists' Collaboration . Collaborative overview of randomised trials of antiplatelet therapy-3: reduction in venous thrombosis and pulmonary embolism by antiplatelet prophylaxis among surgical and medical patients.  BMJ. 1994;  308 235-246
  • 66 Mazzone C, Chiodo F G, Sandercock P, Miccio M, Salvi R. Physical methods for preventing deep vein thrombosis in stroke.  Cochrane Database Syst Rev. 2004;  (4) CD001922

Dr. Alexander T Cohen

Vascular Medicine, Department of Vascular Surgery, King's College Hospital

Bessemer Rd., London SE5 9RS, United Kingdom

Email: alexander.cohen@kcl.ac.uk

    >