Indian Journal of Critical Care Medicine

Register      Login



Volume / Issue

Online First

Related articles

VOLUME 18 , ISSUE 6 ( June, 2014 ) > List of Articles


Thrombo-prophylaxis in acutely ill medical and critically ill patients

Jai Sharma, Dinesh Singh

Keywords : Critically ill, deep vein thrombosis, heparin, mortality, thrombo-prophylaxis

Citation Information : Sharma J, Singh D. Thrombo-prophylaxis in acutely ill medical and critically ill patients. Indian J Crit Care Med 2014; 18 (6):382-391.

DOI: 10.4103/0972-5229.133902

License: CC BY-ND 3.0

Published Online: 01-01-2006

Copyright Statement:  Copyright © 2014; The Author(s).


Thrombo-prophylaxis has been shown to reduce the incidence of pulmonary embolism (PE) and mortality in surgical patients. The purpose of this review is to find out the evidence-based clinical practice criteria of deep vein thrombosis (DVT) prophylaxis in acutely ill medical and critically ill patients. English-language randomized controlled trials, systematic reviews, and meta-analysis were included if they provided clinical outcomes and evaluated therapy with low-dose heparin or related agents compared with placebo, no treatment, or other active prophylaxis in the critically ill and medically ill population. For the same, we searched MEDLINE, PUBMED, Cochrane Library, and Google Scholar. In acutely ill medical patients on the basis of meta-analysis by Lederle et al. (40 trials) and LIFENOX study, heparin prophylaxis had no significant effect on mortality. The prophylaxis may have reduced PE in acutely ill medical patients, but led to more bleeding events, thus resulting in no net benefit. In critically ill patients, results of meta-analysis by Alhazzani et al. and PROTECT Trial indicate that any heparin prophylaxis compared with placebo reduces the rate of DVT and PE, but not symptomatic DVT. Major bleeding risk and mortality rates were similar. On the basis of MAGELLAN trial and EINSTEIN program, rivaroxaban offers a single-drug approach to the short-term and continued treatment of venous thrombosis. Aspirin has been used as antiplatelet agent, but when the data from two trials the ASPIRE and WARFASA study were pooled, there was a 32% reduction in the rate of recurrence of venous thrombo-embolism and a 34% reduction in the rate of major vascular events.

PDF Share
  1. Warkentin TE. Aspirin for dual prevention of venous and arterial thrombosis. N Engl J Med 2012;367:2039-41.
  2. Geerts W, Cook D, Selby R, Etchells E. Venous thromboembolism and its prevention in critical care. J Crit Care 2002;17:95-104.
  3. Ribic C, Lim W, Cook D, Crowther M. Low-molecular-weight heparin thromboprophylaxis in medical-surgical critically ill patients: A systematic review. J Crit Care 2009;24:197-205.
  4. Warwick D, Samama MM. The contrast between venographic and clinical endpoints in trials of thromboprophylaxis in hip replacement. J Bone Joint Surg Br 2000;82:480-2.
  5. Geerts WH, Heit JA, Clagett GP, Pineo GF, Colwell CW, Anderson FA Jr, et al. Prevention of venous thromboembolism. Chest 2001;119:132S-75.
  6. Cade JF. High risk of the critically ill for venous thromboembolism. Crit Care Med 1982;10:448-50.
  7. Alhazzani W, Lim W, Jaeschke RZ, Murad MH, Cade J, Cook DJ. Heparin thromboprophylaxis in medical-surgical critically ill patients: A systematic review and meta-analysis of randomized trials. Crit Care Med 2013;41:2088-98.
  8. 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, Guyatt G, Walter S, Heels-Ansdell D, et al. Dalteparin versus unfractionated heparin in critically ill patients. N Engl J Med 2011;364:1305-14.
  9. Shorr AF, Williams MD. Venous thromboembolism in critically ill patients. Observations from a randomized trial in sepsis. Thromb Haemost 2009;101:139-44.
  10. Kapoor M, Kupfer YY, Tessler S. Subcutaneous heparin prophylaxis significantly reduces the incidence of venous thromboembolic events in the critically ill. Abstr. Crit Care Med 1999;27 Suppl: A69.
  11. Goldhaber SZ, Kett DH, Cusumano CJ. Low molecular weight heparin versus mini-dose unfractionated heparin for prophylaxis against venous thromboembolism in medical intensive care unit patients: A randomized controlled trial. Abstr. J Am Coll Cardiol 2000;35 Suppl: 325A.
  12. Fraisse F, Holzapfel L, Couland JM, Simonneau G, Bedock B, Feissel M, 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 Respir Crit Care Med 2000;161:1109-14.
  13. De A, Roy P, Garg VK, Pandey NK. Low-molecular-weight heparin and unfractionated heparin in prophylaxis against deep vein thrombosis in critically ill patients undergoing major surgery. Blood Coagul Fibrinolysis 2010;21:57-61.
  14. Dahan R, Houlbert D, Caulin C, Cuzin E, Viltart C, Woler M, 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;16:159-64.
  15. Samama MM, Cohen AT, Darmon JY, Desjardins L, Eldor A, Janbon C, 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.
  16. Leizorovicz A, Cohen AT, Turpie AG, Olsson CG, Vaitkus PT, Goldhaber SZ, et al. Randomized, placebo-controlled trial of dalteparin for the prevention of venous thromboembolism in acutely ill medical patients. Circulation 2004;110:874-9.
  17. 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;347:1357-61.
  18. Lowe GD, Sandercock PA, Rosendaal FR. Prevention of venous thromboembolism after major orthopaedic surgery: Is fondaparinux an advance? Lancet 2003;362:504-5.
  19. Lederle FA, Sacks JM, Fiore L, Landefeld CS, Steinberg N, Peters RW, et al. The prophylaxis of medical patients for thromboembolism pilot study. Am J Med 2006;119:54-9.
  20. 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;155:602-15.
  21. Kakkar AK, Cimminiello C, Goldhaber SZ, Parakh R, Wang C, Bergmann JF, et al. Low-molecular-weight heparin and mortality in acutely ill medical patients. N Engl J Med 2011;365:2463-72.
  22. Mahé I, Bergmann JF, d′Azémar P, Vaissie JJ, Caulin C. 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;61:347-51.
  23. Belch JJ, Lowe GD, Ward AG, Forbes CD, Prentice CR. Prevention of deep vein thrombosis in medical patients by low-dose heparin. Scott Med J 1981;26:115-7.
  24. Cohen AT, Davidson BL, Gallus AS, Lassen MR, Prins MH, Tomkowski W, et al. Efficacy and safety of fondaparinux for the prevention of venous thromboembolism in older acute medical patients: Randomised placebo controlled trial. BMJ 2006;332:325-9.
  25. Weber C, Merminod T, Herrmann FR, Zulian GB. Prophylactic anti-coagulation in cancer palliative care: A prospective randomised study. Support Care Cancer 2008;16:847-52.
  26. Harenberg J, Kallenbach B, Martin U, Dempfle CE, Zimmermann R, Kübler W, et al. Randomized controlled study of heparin and low molecular weight heparin for prevention of deep-vein thrombosis in medical patients. Thromb Res 1990;59:639-50.
  27. Aquino JP, Gambier A, Ducros JJ. Prophylaxis of thromboembolic disorders in elderly patients with fraxiparine. In: Bounameaux H, Samama M, ten Cate JW, editors. Fraxiparine: Second International Symposium Recent Pharmacological and Clinical Data. Monte Carlo: Schattauer; 1990.
  28. Harenberg J, Roebruck P, Heene DL. Subcutaneous low-molecular-weight heparin versus standard heparin and the prevention of thromboembolism in medical inpatients. The Heparin Study in Internal Medicine Group. Haemostasis 1996;26:127-39.
  29. 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;76:529-34.
  30. Lechler E, Schramm W, Flosbach CW. The venous thrombotic risk in non-surgical patients: Epidemiological data and efficacy/safety profile of a low-molecular-weight heparin (enoxaparin). The Prime Study Group. Haemostasis 1996;26 Suppl 2:49-56.
  31. Kleber FX, Witt C, Vogel G, Koppenhagen K, Schomaker U, Flosbach CW, et al. 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;145:614-21.
  32. Schellong SM, Haas S, Greinacher A, Schwanebeck U, Sieder C, Abletshauser C, et al. An open-label comparison of the efficacy and safety of certoparin versus unfractionated heparin for the prevention of thromboembolic complications in acutely ill medical patients: CERTAIN. Expert Opin Pharmacother 2010;11:2953-61.
  33. Riess H, Haas S, Tebbe U, Gerlach HE, Abletshauser C, Sieder C, et al. A randomized, double-blind study of certoparin vs. unfractionated heparin to prevent venous thromboembolic events in acutely ill, non-surgical patients: CERTIFY Study. J Thromb Haemost 2010;8:1209-15.
  34. Luba M, Firek A, Kochanowski Z. Two models of thromboprophylaxis in acutely ill medical inpatients. Pol Arch Med Wewn 2007;117:31-7.
  35. Hull RD, Schellong SM, Tapson VF, Monreal M, Samama MM, Nicol P, et al. Extended-duration venous thromboembolism prophylaxis in acutely ill medical patients with recently reduced mobility: A randomized trial. Ann Intern Med 2010;153:8-18.
  36. McCarthy ST, Turner JJ, Robertson D, Hawkey CJ, Macey DJ. Low-dose heparin as a prophylaxis against deep-vein thrombosis after acute stroke. Lancet 1977;2:800-1.
  37. McCarthy ST, Turner J. Low-dose subcutaneous heparin in the prevention of deep-vein thrombosis and pulmonary emboli following acute stroke. Age Ageing 1986;15:84-8.
  38. Turpie AG, Levine MN, Hirsh J, Carter CJ, Jay RM, Powers PJ, et al. Double-blind randomised trial of Org 10172 low-molecular-weight heparinoid in prevention of deep-vein thrombosis in thrombotic stroke. Lancet 1987;1:523-6.
  39. Dickmann U, Voth E, Schicha H, Henze T, Prange H, Emrich D. Heparin therapy, deep-vein thrombosis and pulmonary embolism after intracerebral hemorrhage. Klin Wochenschr 1988;66:1182-3.
  40. Prins MH, Gelsema R, Sing AK, van Heerde LR, den Ottolander GJ. Prophylaxis of deep venous thrombosis with a low-molecular-weight heparin (Kabi 2165/Fragmin) in stroke patients. Haemostasis 1989;19:245-50.
  41. Sandset PM, Dahl T, Stiris M, Rostad B, Scheel B, Abildgaard U. A double-blind and randomized placebo-controlled trial of low molecular weight heparin once daily to prevent deep-vein thrombosis in acute ischemic stroke. Semin Thromb Hemost 1990;16 Suppl: 25-33.
  42. Kay R, Wong KS, Yu YL, Chan YW, Tsoi TH, Ahuja AT, et al. Low-molecular-weight heparin for the treatment of acute ischemic stroke. N Engl J Med 1995;333:1588-93.
  43. The International Stroke Trial (IST): A randomised trial of aspirin, subcutaneous heparin, both, or neither among 19435 patients with acute ischaemic stroke. International Stroke Trial Collaborative Group. Lancet 1997;349:1569-81.
  44. Dumas R, Woitinas F, Kutnowski M, Nikolic I, Berberich R, Abedinpour F, et al. A multicentre, double-blind, randomized study to compare the safety and efficacy of once-daily ORG 10172 and twice-daily low-dose heparin in preventing deep-vein thrombosis in patients with acute ischaemic stroke. Age Ageing 1994;23:512-6.
  45. Turpie AG, Gent M, Côte R, Levine MN, Ginsberg JS, Powers PJ, et al. A low-molecular-weight heparinoid compared with unfractionated heparin in the prevention of deep vein thrombosis in patients with acute ischemic stroke. A randomized, double-blind study. Ann Intern Med 1992;117:353-7.
  46. 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.
  47. Diener HC, Ringelstein EB, von Kummer R, Landgraf H, Koppenhagen K, Harenberg J, 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;37:139-44.
  48. Sherman DG, Albers GW, Bladin C, Fieschi C, Gabbai AA, Kase CS, 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;369:1347-55.
  49. Prasad BK, Banerjee AK, Howard H. Incidence of deep vein thrombosis and the effect of pneumatic compression of the calf in elderly hemiplegics. Age Ageing 1982;11:42-4.
  50. Muir KW, Watt A, Baxter G, Grosset DG, Lees KR. Randomized trial of graded compression stockings for prevention of deep-vein thrombosis after acute stroke. QJM 2000;93:359-64.
  51. CLOTS Trials Collaboration, Dennis M, Sandercock PA, Reid J, Graham C, Murray G, 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;373:1958-65.
  52. Green D, Akuhota V, Eiken M, Feinglass J, Fuller S, Hwang C, et al. Prevention of thromboembolism in stroke rehabilitation patients. Top Stroke Rehabil 1998;5:68-74.
  53. Lacut K, Bressollette L, Le Gal G, Etienne E, De Tinteniac A, Renault A, et al. Prevention of venous thrombosis in patients with acute intracerebral hemorrhage. Neurology 2005;65:865-9.
  54. CLOTS (Clots in Legs or Stockings after Stroke) Trial Collaboration. Thigh-length versus below-knee stockings for deep venous thrombosis prophylaxis after stroke: A randomized trial. Ann Intern Med 2010;153:553-62.
  55. Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuünemann HJ, American College of Chest Physicians Antithrombotic Therapy and Prevention of Thrombosis Panel. Executive summary: Antithrombotic Therapy and Prevention of Thrombosis, 9 th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141 Suppl: 7S-47.
  56. Barbar S, Noventa F, Rossetto V, Ferrari A, Brandolin B, Perlati M, 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;8:2450-7.
  57. 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;83:657-60.
  58. Spencer FA, Emery C, Lessard D, Anderson F, Emani S, Aragam J, et al. The Worcester Venous Thromboembolism study: A population-based study of the clinical epidemiology of venous thromboembolism. J Gen Intern Med 2006;21:722-7.
  59. Hutten BA, Prins MH. Duration of treatment with vitamin K antagonists in symptomatic venous thromboembolism. Cochrane Database Syst Rev 2006;25:CD001367.
  60. 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.
  61. Rodger MA, Kahn SR, Wells PS, Anderson DA, Chagnon I, Le Gal G, et al. Identifying unprovoked thromboembolism patients at low risk for recurrence who can discontinue anticoagulant therapy. CMAJ 2008;179:417-26.
  62. Cohen AT, Spiro TE, Büller HR, Haskell L, Hu D, Hull R, et al. Rivaroxaban for thromboprophylaxis in acutely ill medical patients. N Engl J Med 2013;368:513-23.
  63. Goldhaber SZ, Leizorovicz A, Kakkar AK, Haas SK, Merli G, Knabb RM, et al. Apixaban versus enoxaparin for thromboprophylaxis in medically ill patients. N Engl J Med 2011;365:2167-77.
  64. EINSTEIN Investigators, Bauersachs R, Berkowitz SD, Brenner B, Buller HR, Decousus H, et al. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 2010;363:2499-510.
  65. EINSTEIN-PE Investigators, Büller HR, Prins MH, Lensin AW, Decousus H, Jacobson BF, et al. Oral rivaroxaban for the treatment of symptomatic pulmonary embolism. N Engl J Med 2012;366:1287-97.
  66. Becattini C, Agnelli G, Schenone A, Eichinger S, Bucherini E, Silingardi M, et al. Aspirin for preventing the recurrence of venous thromboembolism. N Engl J Med 2012;366:1959-67.
  67. Brighton TA, Eikelboom JW, Mann K, Mister R, Gallus A, Ockelford P, et al. Low-dose aspirin for preventing recurrent venous thromboembolism. N Engl J Med 2012;367:1979-87.
PDF Share
PDF Share

© Jaypee Brothers Medical Publishers (P) LTD.