Should all acutely ill medical patients be treated with antithrombotic drugs?

 

 Buy Article Permissions and Reprints

Summary

After reports from observational studies suggesting an association between acutely ill medical patients and venous thromboembolism (VTE), interventional trials with anticoagulants drugs have demonstrated a significant reduction of VTE during and immediately after hospitalisation. Although several guidelines suggest the clinical relevance of reducing this outcome, there is a low tendency to use anticoagulants in patients hospitalised for acute medical illness. We speculated that such underuse may be dependent on a low perception that patients included in the trials are actually at risk of thromboembolism. Therefore, the aim of this study was to analyse the clinical settings included in the interventional trials and their relationship with thrombotic risk. Analysis of interventional trials revealed that the majority of patients included in the trials (about 80%) were affected by heart failure, acute respiratory syndrome or infections. Among these three illnesses, literature data shows an association with venous thrombosis only in patients with acute infections; this finding was, however, supported only by retrospective study. On the contrary, there is scarce or no evidence that heart failure and acute respiratory syndrome are associated with venous thrombosis. These data underscore the need of better defining the thrombotic risk profile of acutely ill medical patients included in interventional trials with anticoagulants.

• 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 Int Med 1991; 151: 933-938.
  CrossrefPubMedGoogle Scholar
• 2 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 Int Med 2002; 162: 1245-1248.
  CrossrefPubMedGoogle Scholar
• 3 Samama MM. An epidemiologic study of risk factors for deep vein thrombosis in medical outpatients: the Sirius study. Arch Int Med 2000; 160: 3415-3420.
  CrossrefPubMedGoogle Scholar
• 4 Dahan R, Houlbert D, Caulin C. et al. Prevention of deep vein thrombosis in elderly medical in-patients by a low molecular weight heparin: a randomized double-blind trial. Haemostasis 1986; 16: 159-164.
  PubMedGoogle Scholar
• 5 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: 793-800.
  CrossrefPubMedGoogle Scholar
• 6 Fraisse F, Holzapfel L, Couland JM. et al. Nadroparin in the prevention of deep vein thrombosis in acute decompensated COPD. The Association of Non-University Affiliated Intensive Care Specialist Physicians of France. Am J Resp Crit Care Med 2000; 161: 1109-1114.
  CrossrefPubMedGoogle Scholar
• 7 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: 874-879.
  CrossrefPubMedGoogle Scholar
• 8 Lederle FA, Sacks JM, Fiore L. et al. The prophylaxis of medical patients for thromboembolism pilot study. Am J Med 2006; 119: 54-59.
  PubMedGoogle Scholar
• 9 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: 2463-2472.
  CrossrefPubMedGoogle Scholar
• 10 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 Int Med 2010; 153: 8-18.
  CrossrefPubMedGoogle Scholar
• 11 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. Br Med J 2006; 332: 325-329.
  CrossrefPubMedGoogle Scholar
• 12 Mahe I, Bergmann JF, d’Azemar 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: 347-351.
  CrossrefPubMedGoogle Scholar
• 13 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 (06) 381S-3453S
  CrossrefPubMedGoogle Scholar
• 14 Wittkowsky AK. Effective anticoagulation therapy: defining the gap between clinical studies and clinical practice. Am J Manag Care 2004; 10 (10) S297-306. discussion S12–17
  PubMedGoogle Scholar
• 15 Ageno W. Do medical patients need to receive pharmacologic prophylaxis for the prevention of venous thromboembolism?. Intern Emerg Med 2012; 07 (Suppl. 03) S189-192.
  PubMedGoogle Scholar
• 16 Khoury H, Welner S, Kubin M. et al. Disease burden and unmet needs for prevention of venous thromboembolism in medically ill patients in Europe show underutilisation of preventive therapies. Thromb Haemost 2011; 106: 600-608.
  Article in Thieme ConnectPubMedGoogle Scholar
• 17 Albertsen IE, Larsen TB, Rasmussen LH. et al. Prevention of venous thromboembolism with new oral anticoagulants versus standard pharmacological treatment in acute medically ill patients: a systematic review and meta-analysis. Drugs 2012; 72: 1755-1764.
  CrossrefPubMedGoogle Scholar
• 18 Oger E. Incidence of venous thromboembolism: a community-based study in Western France. EPI-GETBP Study Group. Groupe d’Etude de la Thrombose de Bretagne Occidentale. Thromb Haemost 2000; 83: 657-660.
  Article in Thieme ConnectPubMedGoogle Scholar
• 19 Oger E, Bressollette L, Nonent M. et al. High prevalence of asymptomatic deep vein thrombosis on admission in a medical unit among elderly patients. Thromb Haemost 2002; 88: 592-597.
  Article in Thieme ConnectPubMedGoogle Scholar
• 20 Loh E, Sutton MS, Wun CC. et al. Ventricular dysfunction and the risk of stroke after myocardial infarction. N Engl J Med 1997; 336: 251-257.
  CrossrefPubMedGoogle Scholar
• 21 Howell MD, Geraci JM, Knowlton AA. Congestive heart failure and outpatient risk of venous thromboembolism: a retrospective, case-control study. J Clin Epidemiol 2001; 54: 810-816.
  CrossrefPubMedGoogle Scholar
• 22 Bernard GR, Artigas A, Brigham KL. et al. The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Resp Crit Care Med 1994; 149: 818-824.
  CrossrefPubMedGoogle Scholar
• 23 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: 1075-1079.
  CrossrefPubMedGoogle Scholar
• 24 Levi M, Keller TT, van Gorp E. et al. Infection and inflammation and the coagulation system. Cardiovasc Res 2003; 60: 26-39.
  CrossrefPubMedGoogle Scholar
• 25 Fitzgerald JR, Foster TJ, Cox D. The interaction of bacterial pathogens with platelets. Nature Rev Microbiol 2006; 04: 445-457.
  CrossrefPubMedGoogle Scholar
• 26 Alikhan R, Cohen AT, 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.
  CrossrefPubMedGoogle Scholar
• 27 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: 190-196.
  Article in Thieme ConnectPubMedGoogle Scholar
• 28 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.;
  Google Scholar