Download PDF
Semin Vasc Med 2001; 01(1): 061-070
DOI: 10.1055/s-2001-14542
Copyright © 2001 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Prevention of Venous Thromboembolism in High-Risk Surgical and Medical Patients

Paolo Prandoni, Paola Sabbion, Cinzia Tanduo, Gabriella Errigo, Ezio Zanon, Enrico Bernardi
  • Department of Medical and Surgical Sciences, University of Padua Medical School, Padua, Italy
Further Information

Publication History

Publication Date:
31 December 2001 (online)

    Permissions and Reprints

ABSTRACT

Although pharmacologic prophylaxis against venous thromboembolism has become the standard of care following total hip and knee replacement, prophylaxis among patients undergoing surgery for hip fracture and other lower extremity trauma remains underutilized. Available experience consistently supports the view that low-molecular-weight heparins are more effective than unfractionated heparin for prevention of proximal deep vein thrombosis (DVT) with no additional hemorrhagic risk and more effective than oral anticoagulants for prevention of in-hospital (mostly distal) venous thrombosis at the price of a higher surgical site bleeding and wound hematoma. The choice between low-molecular-weight heparin and warfarin should be tailored to the individual patients based on the clinical assessment of postoperative thrombosis and bleeding risk as well as the prophylaxis-specific cost and convenience. Whether thromboprophylaxis should be continued for a few additional weeks after hospital discharge is controversial.

The overall incidence of postoperative DVT in patients with cancer is about twice as high as that of patients free of malignancy. Accordingly, they require prophylactic measures comparable with those usually recommended for major orthopedic surgery. In this setting, dermatan sulfate shows promise.

In contrast to surgical patients, prevention of venous thromboembolism is less well studied in hospitalized medical patients. In a recent controlled randomized trial, enoxaparin in high prophylactic doses was an effective and safe measure of thromboprophylaxis in ordinary bedridden patients.

KEYWORD

Venous thromboembolism - thromboprophylaxis - deep vein thrombosis - postoperative

REFERENCES

  • 1 Clagett G P, Anderson Jr A F, Geerts W A. Prevention of venous thromboembolism.  Chest . 1998;  531-560 (531-560)
    PubMedGoogle Scholar
  • 2 Consensus Statement. Prevention of venous thromboembolism.  Intern Angiol . 1997;  16 3-38
    PubMedGoogle Scholar
  • 3 Janku G V, Paiement G D, Green H D. Prevention of venous thromboembolism in orthopaedics in the United States.  Clin Orthop . 1996;  4 313-321
    PubMedGoogle Scholar
  • 4 Laverick M D, Croal S A, Mollan R AB. Orthopaedic surgeons and thromboprophylaxis.  Br Med J . 1991;  303 549-450
    PubMedGoogle Scholar
  • 5 Stratton M A, Anderson F A, Bussey H I. Prevention of venous thromboembolism. Adherence to the 1995 American College of Chest Physicians Consensus Guidelines for surgical patients.  Arch Intern Med . 2000;  160 334-340
    CrossrefPubMedGoogle Scholar
  • 6 Hull R, Raskob G, Pineo G. A comparison of subcutaneous low-molecular-weight heparin with warfarin sodium for prophylaxis against deep-vein thrombosis after hip or knee implantation.  N Engl J Med . 1993;  329 1370-1376
    CrossrefPubMedGoogle Scholar
  • 7 Lowe G DO, Haverkate F, Thompson S G. Prediction of deep vein thrombosis after elective hip replacement surgery by preoperative clinical and haemostatic variables: the ECAT DVT Study.  Thromb Haemost . 1999;  81 879-886
    PubMedGoogle Scholar
  • 8 Ryan D H, Crowther M A, Ginsberg J S, Francis C W. Relation of factor V Leiden genotype to risk for acute deep venous thrombosis after joint replacement surgery.  Ann Intern Med . 1998;  128 270-276
    PubMedGoogle Scholar
  • 9 Lindahl T L, Lundahl T H, Nilsson L, Andersson C A. APC-resistance is a risk factor for postoperative thromboembolism in elective replacement of the hip or knee. A prospective study.  Thromb Haemost . 1999;  81 18-21
    PubMedGoogle Scholar
  • 10 Anderson D R, O'Brien B J, Levine M N, Roberts R, Wells P S, Hirsh J. Efficacy and cost of low-molecular-weight heparin compared with standard heparin for the prevention of deep vein thrombosis after total hip arthroplasty.  Ann Intern Med . 1993;  19 1105-1112
    PubMedGoogle Scholar
  • 11 Kakkar V V, Howes J, Sharma V, Kadziola Z. A comparative, double-blind, randomised trial of a new second generation LMWH (Beniparin) and UFH in the prevention of post-operative venous thromboembolism.  Thromb Haemost . 2000;  83 523-529
    PubMedGoogle Scholar
  • 12 RD Heparin Arthroplasty Group. RD heparin compared with warfarin for prevention of venous thromboembolic disease following total hip or knee arthroplasty.  J Bone Joint Surg . 1994;  76-A 1174-1185
    PubMedGoogle Scholar
  • 13 Hamulyak K, Lensing A WA, van der Meer J, Smid W M, van Ooy A, Hoek J A, for the Fraxiparine Oral Anticoagulant Study Group. Subcutaneous low-molecular-weight heparin or oral anticoagulants for the prevention of deep-vein thrombosis in elective hip and knee replacement?.  Thromb Haemostas . 1995;  74 1428-1431
    PubMedGoogle Scholar
  • 14 Leclerc J R, Geerts W H, Desjardins L. Prevention of venous thromboembolism after knee arthroplasty. A randomized, double-blind trial comparing enoxaparin with warfarin.  Ann Intern Med . 1996;  124 619-626
    PubMedGoogle Scholar
  • 15 Francis C W, Pellegrini V D, Totterman S. Prevention of deep-vein thrombosis after total hip arthroplasty. Comparison of warfarin and dalteparin.  J Bone Joint Surg . 1997;  79A 1365-1372
    PubMedGoogle Scholar
  • 16 Hull R D, Pineo G F, Francis C. Low-molecular-weight heparin prophylaxis using dalteparin in close proximity to surgery vs warfarin in hip arthroplasty patients: a double-blind, randomized comparison. The North American Fragmin Trial Investigators.  Arch Intern Med . 2000;  160 2199-2207
    CrossrefPubMedGoogle Scholar
  • 17 Colwell C W, Collis D K, Paulson R. Comparison of enoxaparin and warfarin for the prevention of venous thromboembolic disease after total hip arthroplasty. Evaluation during hospitalization and three months after discharge.  J Bone Joint Surg . 1999;  81-A 932-940
    PubMedGoogle Scholar
  • 18 Palmer A J, Koppenhagen K, Kirchhof B, Weber U, Bergemann R. Efficacy and safety of low molecular weight heparin, unfractionated hepatrin and warfarin for thrombo-embolism prophylaxis in orthopaedic surgery: a meta-analysis of randomised clinical trials.  Haemostasis . 1997;  27 75-84
    PubMedGoogle Scholar
  • 19 Honward A W, Aaron S D. Low molecular weight heparin decreases proximal and distal deep-venous thrombosis following total knee arthroplasty.  Thromb Haemost . 1998;  79 902-906
    PubMedGoogle Scholar
  • 20 Hull R D, Raskob G E, Pineo G F. Subcutaneous low-molecular-weight heparin vs warfarin for prophylaxis of deep vein thrombosis after hip or knee implantation. An economic perspective.  Arch Intern Med . 1997;  157 298-303
    CrossrefPubMedGoogle Scholar
  • 21 Bergqvist D, Benoni G, Bjorgell O. Low-molecular-weight heparin (enoxaparin) as prophylaxis against venous thromboembolism after total hip replacement.  N Engl J Med . 1996;  335 696-700
    CrossrefPubMedGoogle Scholar
  • 22 Planes A, Vochelle N, Darmon J Y, Fagola M, Bellaud M, Huet Y. Risk of deep-venous thrombosis after hospital discharge in patients having undergone total hip replacement: double-blind randomized comparison of enoxaparin versus placebo.  Lancet . 1996;  348 224-228
    CrossrefPubMedGoogle Scholar
  • 23 Lassen M R, Borris L C, Anderson B S. Efficacy and safety of prolonged thromboprophylaxis with a low molecular weight heparin (Dalteparin) after total hip arthroplasty. The Danish Prolonged Prophylaxis Study.  Thromb Res . 1998;  89 281-287
    CrossrefPubMedGoogle Scholar
  • 24 Dahl O E, Andreassen G, Aspelin T. Prolonged thromboprophylaxis following hip replacement surgery. Results of a double-blind, prospective, randomised, placebo-controlled study with dalteparin (Fragmin).  Thromb Haemost . 1997;  77 26-31
    PubMedGoogle Scholar
  • 25 Hull R D, Pineo G F, Francis C. Low-molecular-weight heparin prophylaxis using dalteparin extended out-of-hospital vs.  in-hospital warfarin/out-of-hospital placebo in hip arthroplasty patients. A double-blind, randomised comparison. Arch Intern Med . 2000;  160 2208-2215
    CrossrefPubMedGoogle Scholar
  • 26 Manganelli D, Pazzagli M, Mazzantini D. Prolonged prophylaxis with unfractionated heparin is effective to reduce delayed deep vein thrombosis in total hip replacement.  Respiration . 1998;  65 369-374
    CrossrefPubMedGoogle Scholar
  • 27 Warwick D, Williams M H, Bannister G C. Death and thromboembolic disease after total hip replacement. A series of 1162 cases with no routine chemical prophylaxis.  J Bone Joint Surg . 1995;  77-B 6-10
    PubMedGoogle Scholar
  • 28 Leclerc J R, Gent M, Hirsh J, Geerts W H, Ginsberg J S, for the Canadian Collaborative Group. The incidence of symptomatic venous thromboembolism during and after prophylaxis with enoxaparin.  Arch Intern Med . 1998;  158 873-878
    CrossrefPubMedGoogle Scholar
  • 29 Heit J A, Elliott G, Trowbridge A A, Morrey B F, Gent M, Hirsh J, for the Ardeparin Arthroplasty Study Group. Ardeparin sodium for extended out-of-hospital prophylaxis against venous thromboembolism after total hip or knee replacement.  Ann Intern Med . 2000;  132 853-861
    PubMedGoogle Scholar
  • 30 Robinson K S, Anderson D R, Gross M. Ultrasonographic screening before hospital discharge for deep venous thrombosis after arthroplasty: the post-arthroplasty screening study.  Ann Intern Med . 1997;  127 439-445
    PubMedGoogle Scholar
  • 31 Verlato F, Bruchi O, Prandoni P. The value of ultrasound screening for proximal vein thrombosis after total hip arthroplasty.  Thromb Haemost (in press).
    PubMedGoogle Scholar
  • 32 Agnelli G, Ranucci V, Veschi F, Rinonapoli E, Lupattelli L, Nenci G G. Clinical outcome of orthopaedic patients with negative lower limb venography at discharge.  Thromb Haemost. 1995;  74 1042-1044
    PubMedGoogle Scholar
  • 33 Ricotta S, Iorio A, Parise P, Nenci G G, Agnelli G. Postdischarge clinically overt venous thromboembolism in orthopaedic surgery patients with negative venography-an overview analysis.  Thromb Haemost . 1996;  76 887-892
    PubMedGoogle Scholar
  • 34 Pulmonary Embolism Prevention (PEP) Trial Collaborative Group. Prevention of pulmonary embolism and deep vein thrombosis with low dose aspirin: Pulmonary Embolism Prevention (PEP) trial.  Lancet . 2000;  355 1295-1302
    CrossrefPubMedGoogle Scholar
  • 35 Kearon C, Hirsh J. Starting prophylaxis postoperatively.  Arch Intern Med . 1995;  4 366-372
    PubMedGoogle Scholar
  • 36 Hull R D, Brant R F, Pineo G F, Stein P D, Raskob G E, Valentine K A. Pre-operative vs post-operative initiation of low-molecular-weight heparin prophylaxis against venous thromboembolism in patients undergoing elective hip replacement.  Arch Intern Med . 1999;  159 137-141
    CrossrefPubMedGoogle Scholar
  • 37 Palareti G, Borghi B, Coccheri S. Postoperative versus preoperative initiation of deep-vein thrombosis prophylaxis with a low-molecular-weight heparin (Nadroparin) in elective hip replacement.  Clin Appl Thrombosis Hemostasis . 1996;  2 18-24
    PubMedGoogle Scholar
  • 38 Jorgensen P S, Strandberg C, Wille-Jorgensen P. Early preoperative thromboprophylaxis with Klexane in hip fracture surgery: a placebo-controlled study.  Clin Appl Thromb Haemost . 1998;  4 141-142
    PubMedGoogle Scholar
  • 39 Prins M H, Hirsh J. A comparison of general anesthesia and regional anesthesia as a risk factor for deep vein thrombosis following hip surgery. A critical review.  Thromb Haemostas . 1990;  64 497-500
    PubMedGoogle Scholar
  • 40 Lumpkin M M. FDA Alert. FDA public health advisory.  Anesthesiology . 1998;  88 27A-28A
    PubMedGoogle Scholar
  • 41 Eriksson B, Wille-Jorgensen P, Kalebo P. A comparison of recombinant hirudin with a low-molecular-weight heparin to prevent thromboembolic complications after total hip replacement.  N Engl J Med . 1997;  337 1329-1335
    CrossrefPubMedGoogle Scholar
  • 42 Eriksson B I, Lindbratt J S, Kalebo P. Methro II: dose-response study of the novel oral, direct thrombin inhibitor, H 376/95 and its subcutaneous formulation melagatran, compared with dalteparin as thromboembolic prophylaxis after total hip or total knee replacement.  Haemostasis . 2000;  20-21 (20-21)
    PubMedGoogle Scholar
  • 43 Samama M M, Bara L, Walenga J. Comparative mechanism of action and pharmacokinetics of pentasaccharide and LMW heparins. 16th International Congress on Thrombosis, Portugal.  State of the Art. 2000;  20-21
    PubMedGoogle Scholar
  • 44 Kakkar V V, Howe C T, Nicolaides A N, Renney J TG, Clarke M B. Deep vein thrombosis of the leg. Is there a ``high risk'' group?.  Am J Surg . 1970;  120 527-530
    Google Scholar
  • 45 Hills N H, Pflug J J, Jeyasingh K, Boardman L, Calnan J S. Prevention of deep vein thrombosis by intermittent pneumatic compression of calf.  Br Med J . 1972;  1 131-135
    PubMedGoogle Scholar
  • 46 Walsh J J, Bonnar J, Wright F W. A study of pulmonary embolism and deep vein thrombosis after major gynaecological surgery using labelled fibrinogen-phlebography and lung scanning.  J Obstet Gynaecol Br Commonw . 1974;  81 311-316
    PubMedGoogle Scholar
  • 47 Sue-Ling H M, Johnston D, McMahon M U, Philips P R, Davies J A. Preoperative identification of patients at high risk of deep venous thrombosis after elective major abdominal surgery.  Lancet . 1986;  1 1173-1176
    PubMedGoogle Scholar
  • 48 Rosemberg I L, Evans M, Pollock A V. Prophylaxis of postoperative leg vein thrombosis by low dose subcutaneous heparin or peroperative calf muscles stimulation: a controlled clinical trial.  Br Med J . 1975;  1 649-651
    PubMedGoogle Scholar
  • 49 Allan A, Williams J T, Bolton J P, Le Quesne P L. The use of graduated compression stockings in the prevention of postoperative deep vein thrombosis.  Br J Surg . 1983;  70 172-174
    CrossrefPubMedGoogle Scholar
  • 50 Multicentre Trial Committee. Dihydroergotamine-heparin prophylaxis of postoperative deep vein thrombosis: a multicentre trial.  JAMA . 1984;  251 2960-2966
    CrossrefPubMedGoogle Scholar
  • 51 Huber O, Bounameaux H, Borst F, Rohner A. Postoperative pulmonary embolism after hospital discharge. An underestimated risk.  Arch Surg . 1992;  127 310-313
    CrossrefPubMedGoogle Scholar
  • 52 Godwin J. Use of low molecular weight heparins in malignancy-related thromboembolic disorders: a clinical review.  Clin Appl Thromb Hemost . 1996;  28-34 (28-34)
    PubMedGoogle Scholar
  • 53 Enoxacan Study group. Efficacy and safety of enoxaparin versus unfractionated heparin for prevention of deep vein thrombosis in elective cancer surgery: a double-blind randomized multicentre trial with venographic assessment.  Br J Surg . 1997;  84 1099-1103
    CrossrefPubMedGoogle Scholar
  • 54 Bergqvist D, Burmark U S, Flordal P A. Low molecular weight heparin started before surgery as prophylaxis against deep vein thrombosis: 2500 versus 5000 XaI units in 2070 patients.  Br J Surg . 1995;  82 496-501
    CrossrefPubMedGoogle Scholar
  • 55 Gallus A, Cade J, Ockelford P. Orgaran (Org 10172) or heparin for preventing venous thrombosis after elective surgery for malignant disease?.  <~>A double-blind, randomised, multicenter comparison. Thromb Haemost . 1993;  70 562-567
    PubMedGoogle Scholar
  • 56 Di Carlo V, Agnelli G, Prandoni P. Dermatan sulphate for the prevention of postoperative venous thromboembolism in patients with cancer.  Thromb Haemost . 1999;  82 30-34
    PubMedGoogle Scholar
  • 57 Nicolaides A N, Irving D. Clinical factors and the risk of deep venous thrombosis. In: Nicolaides AN, ed. Thromboembolism: Aetiology, Advances in Prevention and Management Lancaster, England: MTP Press 1975: 193-204
    Google Scholar
  • 58 Flordal P A, Bergqvist D, Burmark U S, Ljungström K G, Törngren S. Risk factors for major thromboembolism and bleeding tendency after elective general surgical operations.  Eur J Surg . 1996;  162 783-789
    PubMedGoogle Scholar
  • 59 Thromboembolic Risk Factors Consensus Group. Risk of and prophylaxis for venous thromboembolism in hospital patients.  Br Med J . 1992;  79 1-17
    PubMedGoogle Scholar
  • 60 Brown M, Glassenberg M. Mortality factors in patients with acute stroke.  JAMA . 1973;  224 1493-1495
    CrossrefPubMedGoogle Scholar
  • 61 McCarthy S T, Turner J J, Robertson D. Low dose heparin as a prophylaxis against deep vein thrombosis after acute stroke.  Lancet . 1977;  2 800-801
    PubMedGoogle Scholar
  • 62 Prins M H, den Ottolander J H G, Gelsema R. Prophylaxis of deep venous thrombosis with a low molecular weight heparin (Kabi 2165) in stroke patients.  Haemostasis . 1989;  19 245-250
    PubMedGoogle Scholar
  • 63 Sandset P M, 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;  25-33 (25-33)
    PubMedGoogle Scholar
  • 64 Dumas R, Woitinas F, Kutnowski M. 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;  23 512-516
    PubMedGoogle Scholar
  • 65 McCarthy S T, Turner J. Low-dose subcutaneous heparin in the prevention of deep-vein thrombosis and pulmonary emboli following acute stroke.  Age Ageing . 1986;  15 84-88
    CrossrefPubMedGoogle Scholar
  • 66 Turpie A GG, Gent M, Côte R. A low molecular weight heparinoid compared with unfractionated heparin in the prevention of deep vein thrombosis in patients with acute ischemic stroke.  Ann Intern Med . 1992;  117 353-357
    PubMedGoogle Scholar
  • 67 Turpie A GG, Levine M N, Hirsh J. A double-blind randomized trial of ORG 10172 low molecular weight heparinoid in the prevention of deep vein thrombosis in thrombotic stroke.  Lancet . 1987;  1 523-526
    PubMedGoogle Scholar
  • 68 Kay R, Wong K S, Yu Y L. Low-molecular-weight heparin for the treatment of acute ischemic stroke.  N Engl J Med . 1995;  333 1588-1593
    CrossrefPubMedGoogle Scholar
  • 69 Waring W P, Karunas R S. Acute spinal cord injury and the incidence of clinically occurring thromboembolic disease.  Paraplegia . 1991;  29 8-16
    PubMedGoogle Scholar
  • 70 Green D, Lee M Y, Ito V Y. Fixed- vs adjusted-dose heparin in the prophylaxis of thromboembolism in spinal cord injury.  JAMA . 1988;  260 1255-1258
    CrossrefPubMedGoogle Scholar
  • 71 Green D, Lee M Y, Lim A C. Prevention of thromboembolism after spinal cord injury using low-molecular weight heparin.  JAMA . 1990;  113 571-574
    PubMedGoogle Scholar
  • 72 Merli G J, Crabbe S, Doyle L. Mechanical plus pharmacological prophylaxis for deep vein thrombosis in acute spinal cord injury.  Paraplegia . 1992;  30 558-562
    PubMedGoogle Scholar
  • 73 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
    CrossrefPubMedGoogle Scholar
  • 74 Harvey W P, Finch C A. Dicumarol prophylaxis in thromboembolic disease in congestive heart failure.  N Engl J Med . 1950;  242 208-211
    CrossrefPubMedGoogle Scholar
  • 75 Belch J J, Lowe G DO, Ward A G. Prevention of deep venous thrombosis in medical patients by low-dose heparin.  Scott Med J . 1981;  26 115-117
    PubMedGoogle Scholar
  • 76 Emerson P A, Marks P. Prevention of thromboembolism after myocardial infarction: effect of low-dose heparin or smoking.  Br Med J . 1977;  1 18-20
    PubMedGoogle Scholar
  • 77 Marks P, Teather D. Subcutaneous heparin: a logical prophylaxis for deep-vein thrombosis after myocardial infarction.  Practitioner . 1978;  220 425-429
    PubMedGoogle Scholar
  • 78 Murray T S, Lorimer A R, Cox F C, Lawrie T DV. Leg vein thrombosis following myocardial infarction.  Lancet . 1970;  2 792-723
    PubMedGoogle Scholar
  • 79 Simmons A V, Sheppard M A, Cox A F. Deep venous thrombosis after myocardial infarction. Predisposing factors.  Br Heart J . 1973;  35 623-625
    PubMedGoogle Scholar
  • 80 Warlow C, Beattie A G, Terry G, Ogston D, Kenmure A C, 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
    PubMedGoogle Scholar
  • 81 Pitt A, Anderson S T, Habersberger P G, Rosengarten D S. Low-dose heparin in the prevention of deep-vein thromboses in patients with acute myocardial infarction.  Am Heart J . 1980;  99 574-579
    CrossrefPubMedGoogle Scholar
  • 82 Harvey W P, Finch C A. Dicumarol prophylaxis of thromboembolic disease in congestive heart failure.  N Engl J Med . 1950;  242 208-211
    CrossrefPubMedGoogle Scholar
  • 83 Medical Research Council. Assessment of short-term anticoagulant administration after cardiac infarction.  BMJ . 1969;  1 335-342
    PubMedGoogle Scholar
  • 84 Drapkin A, Merskey C. Anticoagulant therapy after acute myocardial infarction.  JAMA . 1972;  222 541-548
    CrossrefPubMedGoogle Scholar
  • 85 Veterans Administration. Anticoagulants in acute myocardial infarction.  JAMA . 1973;  225 724-729
    CrossrefPubMedGoogle Scholar
  • 86 Gallus A S, Hirsh J, Tuttle R J. Small subcutaneous doses of heparin in prevention of venous thrombosis.  N Engl J Med . 1973;  288 545-551
    PubMedGoogle Scholar
  • 87 Moser K M, LeMoine J R, Nachtwey F J, Spragg R G. Deep venous thrombosis and pulmonary embolism. Frequency in a respiratory intensive care unit.  JAMA . 1981;  246 1422-1424
    CrossrefPubMedGoogle Scholar
  • 88 Ibarra-Perez C, Lau-Cortes E, Colmenero-Zubiate S. Prevalence and prevention of deep venous thrombosis of the lower extremities in high-risk pulmonary patients.  Angiology . 1988;  39 505-513
    PubMedGoogle Scholar
  • 89 Cade J F. High risk of the critically ill for venous thromboembolism.  Crit Care Med . 1982;  10 448-450
    CrossrefPubMedGoogle Scholar
  • 90 Hirsch D R, Ingenito E P, Goldhaber S Z. Prevalence of deep venous thrombosis among patients in medical intensive care.  JAMA . 1995;  274 335-337
    CrossrefPubMedGoogle Scholar
  • 91 Samama M, Cohen A T, Darmon J Y, et al. for the Prohylaxis 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;  341 793-800
    CrossrefPubMedGoogle Scholar
  • 92 Mismetti P, Laporte-Simitsidis S, Tardy B. 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 14-19
    PubMedGoogle Scholar