Semin Thromb Hemost 2006; 32(8): 755-766
DOI: 10.1055/s-2006-955458
Copyright © 2006 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA.

Prevention of Venous Thromboembolism

Mario Pini1 , Alex C. Spyropoulos2
  • 1Medicina Interna II, Ospedale di Fidenza, Fidenza, Parma, Italy
  • 2Clinical Thrombosis Center, Lovelace Medical Center Albuquerque, New Mexico
Further Information

Publication History

Publication Date:
15 December 2006 (online)

ABSTRACT

Patients with clinical conditions such as surgery, trauma, and acute medical illness have a transiently increased risk of venous thromboembolism and merit consideration for adequate thromboprophylaxis. The choice of an appropriate pharmacologic or physical means of prophylaxis should be made taking into account both the thrombotic and bleeding risk associated with patient-related factors and the type of surgery or other disease state involved. A large number of randomized clinical trials, meta-analyses, and guidelines developed by scientific societies worldwide have addressed this issue and have provided information and recommendations that should be considered carefully. The aim of this review is to provide the practicing physician with a brief updated summary of the subject, stratifying those patients at low thrombotic risk who do not require specific thromboprophylaxis apart from early ambulation, from those at moderate or higher thrombotic risk. Patients at moderate thrombotic risk face a 10 to 20% risk of deep vein thrombosis (DVT) and require prophylaxis with low-dose unfractionated heparin or low molecular weight heparins (LMWHs) at a dosage < 3400 U once daily, or with graduated elastic stockings if their bleeding risk is high. Patients with an expected 20 to 40% DVT rate without prophylaxis are considered at high thrombotic risk and should be treated preferentially with LMWHs at high prophylactic dosage (> 3400 U). Patients undergoing major orthopedic surgery face a DVT rate > 40%, are considered at very high risk of venous thromboembolism, and should be given either LMWHs at high prophylactic dosage, fondaparinux, or vitamin K antagonists-either alone or in association with intermittent pneumatic compression devices.

REFERENCES

  • 1 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
  • 2 Gallus A S, Hirsh J, O'Brien S E, McBride J A, Tuttle R J, Gent M. Prevention of venous thromboembolism with small subcutaneous doses of heparin.  JAMA. 1976;  235 1980-1982
  • 3 Kakkar V V, Corrigan T P, Fossard D P. Prevention of fatal postoperative pulmonary embolism by low dose of heparin. An international multicentre trial.  Lancet. 1975;  2 45-51
  • 4 Warkentin T E, Levine M N, Hirsh J et al.. Heparin-induced thrombocytopenia in patients treated with low molecular weight heparin or unfractionated heparin.  N Engl J Med. 1995;  332 1330-1335
  • 5 Pini M, Froehlich J, Bergmann J F et al.. Comparison of US and European practices in the prevention of venous thromboembolism in hospitalized medical patients: findings from the International Medical Prevention Registry on Venous Thromboembolism (IMPROVE).  Blood. 2003;  11 320(Abst)
  • 6 Hirsh J. Low molecular weight heparin.  Thromb Haemost. 1993;  70 204-207
  • 7 Petitou M, Lormeau J C, Choay J. Chemical synthesis of glycosaminoglycans: new appoach to antithrombotic drugs.  Nature. 1991;  350(suppl) 30-33
  • 8 Eriksson B I, Bauer K A, Lassen M R et al.. Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after hip-fracture surgery.  N Engl J Med. 2001;  345 1298-1304
  • 9 Bauer K A, Eriksson B I, Lassen M R et al.. Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after elective major knee surgery.  N Engl J Med. 2001;  345 1305-1310
  • 10 Lassen M R, Bauer K A, Eriksson B I et al.. Postoperative fondaparinux versus preoperative enoxaparin for prevention of venous thromboembolism in elective hip-replacement surgery: a randomised double-blind comparison.  Lancet. 2002;  359 1715-1720
  • 11 Turpie A G, Bauer K A, Eriksson B I et al.. Postoperative fondaparinux versus postoperative enoxaparin for prevention of venous thromboembolism in elective hip replacement surgery: a randomised double blind trial.  Lancet. 2002;  359 1721-1726
  • 12 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 1058-1070
  • 13 Wells P S, Lensing AWA, Hirsh J. Graduated compression stockings in the prevention of postoperative venous thromboembolism.  Arch Intern Med. 1994;  154 67-72
  • 14 Amarigiri S V, Lees T A. Elastic compression stockings for prevention of deep vein thrombosis.  Cochrane Database Syst Rev. 2000;  1 , CD001484
  • 15 Borly L, Wille-Jørgensen P, Rasmussen M S. Systematic review of thromboprophylaxis in colorectal surgery-an update.  Colorectal Dis. 2005;  7 122-127
  • 16 Muhe E. Intermittent sequential high-pressure compression of the leg: a new method of preventing deep vein thrombosis.  Am J Surg. 1984;  147 781-785
  • 17 Hull R D, Raskob G E, Gent M et al.. Effectiveness of intermittent pneumatic leg compression for preventing deep vein thrombosis after total hip replacement.  JAMA. 1990;  263 2313-2317
  • 18 Turpie A G, Hirsh J, Gent M, Julian D, Johnson J. Prevention of deep vein thrombosis in potential neurosurgical patients: a randomised trial comparing graduated compression stockings alone or graduated compression stockings plus intermittent pneumatic compression with control.  Arch Intern Med. 1989;  149 679-681
  • 19 Vaughn B K, Knezevich S, Lombardi Jr A V, Mallory T H. Use of the Greenfield filter to prevent fatal embolism associated with total hip and knee arthroplasty.  J Bone Joint Surg (Am). 1989;  71 1542-1548
  • 20 Nicolaides A N, Bergqvist D, Hull R et al.. Prevention of venous thromboembolic events: International Consensus Statement (guidelines according to scientific evidence).  Int Angiol. 1997;  16 3-38
  • 21 Ageno W. Applying risk assessment models in general surgery: overview of our clinical experience.  Blood Coagul Fibrinolysis. 1999;  10(suppl) S71-S78
  • 22 Bergqvist D, Lindblad B, Matzsch T. Risk of combining low molecular weight heparin for thromboprophylaxis and epidural or spinal anesthesia.  Semin Thromb Hemost. 1993;  19(suppl) 147-151
  • 23 Wysowski D K, Talarico L, Bacsanyi J, Botstein P. Spinal and epidural haematoma and low molecular weight heparin.  N Engl J Med. 1998;  338 1774-1775
  • 24 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 1162-1173
  • 25 Clagett G P, Reisch J S. Prevention of venous thromboembolism in general surgical patients: results of meta-analysis.  Ann Surg. 1988;  208 227-240
  • 26 Mismetti P, Laporte S, Darmon J Y, Buchmuller A, Decousus H. Meta-analysis of low molecular weight heparin in the prevention of venous thromboembolism in general surgery.  Br J Surg. 2001;  88 913-930
  • 27 Nurmohamed M T, Rosendaal F R, Büller H R et al.. Low molecular weight heparin versus standard heparin in general and orthopedic surgery: a meta-analysis.  Lancet. 1992;  340 152-156
  • 28 Leizorovicz A, Haugh M C, Chapuis F R, Samama M M, Boissel J P. Low molecular weight heparins in the prevention of post-operative thrombosis.  BMJ. 1992;  305 913-920
  • 29 Kakkar V V, Murray W J. Efficacy and safety of low-molecular-weight heparin (CY216) in preventing postoperative venous thrombo-embolism: a co-operative study.  Br J Surg. 1985;  98 266a
  • 30 The European Fraxiparin Study Group . Comparison of a low molecular weight and unfractionated heparin for the prevention of deep vein thrombosis in patients undergoing abdominal surgery.  Br J Surg. 1988;  75 1058-1063
  • 31 Koch A, Bouges S, Ziegler S, Dinkel H, Daures J P, Victor N. Low molecular weight heparin and unfractionated heparin in thrombosis prophylaxis after major surgical interventions: update of previous meta-analyses.  Br J Surg. 1997;  84 750-759
  • 32 Bergqvist D, Burmark U S, Flordal P A et al.. 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
  • 33 Kakkar V V, Cohen A, Edmonson R A et al.. Low molecular weight versus standard heparin for prevention of venous thromboembolism after major abdominal surgery. The Thromboprophylaxis Collaborative Group.  Lancet. 1993;  341 259-264
  • 34 Bergqvist D, Agnelli G, Cohen A T et al.. Duration of prophylaxis against venous thromboembolism with enoxaparin after surgery for cancer.  N Engl J Med. 2002;  346 975-980
  • 35 Wille-Jørgensen P. Low dosage heparin combined with either dihydroergotamine or graduated supportive stockings. Combined prevention of thrombosis in colonic surgery.  Ugeskr Laeger. 1986;  148 501-503
  • 36 Wille-Jørgensen P, Hauch O, Dimo B, Christensen S W, Jensen R, Hansen B. Prophylaxis of deep venous thrombosis after acute abdominal operations.  Surg Gynecol Obstet. 1991;  172 44-48
  • 37 Agnelli G, Bergqvist D, Cohen A et al.. Randomized double-blind study to compare the efficacy and safety of postoperative fondaparinux (Arixtra) and preoperative dalteparin in the prevention of venous thromboembolism after high-risk abdominal surgery: the Pegasus Study.  Blood. 2003;  102 13a
  • 38 Riber C, Alstrup N, Nymann T, Bogstad J W, Wille-Jørgensen P, Tonnesen H. Postoperative thromboembolism after day-case herniorrhaphy.  Br J Surg. 1996;  83 420-421
  • 39 Baca I, Schneider B, Kohler T, Misselwitz F, Zehle A, Muhe F. Prevention of venous thromboembolism in patients undergoing minimally invasive interventions and brief inpatient treatment: Results of a multicenter, prospective, randomized, controlled study with a low-molecular-weight heparin.  Chirurgia (Bucur). 1997;  68 1275-1280
  • 40 Bounameaux H, Didier D, Polat O, Desmarais S, de Moerloose P, Huber O. Antithrombotic prophylaxis in patients undergoing laparoscopic cholecystectomy.  Thromb Res. 1997;  86 271-273
  • 41 White R H, Zhou H, Romano P S. Incidence of symptomatic venous thromboembolism after different elective or urgent surgical procedures.  Thromb Haemost. 2003;  90 446-455
  • 42 Donat R, Mancey-Jones B. Incidence of thromboembolism after transurethral resection of the prostate (TURP): a study on TED stockings prophylaxis and literature review.  Scand J Urol Nephrol. 2002;  36 119-123
  • 43 Kucher N, Koo S, Quiroz R et al.. Electronic alerts to prevent venous thromboembolism among hospitalized patients.  N Engl J Med. 2005;  352 969-977
  • 44 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 Br. 1995;  77 6-10
  • 45 Khaw F M, Moran C G, Pinder I M, Smith S R. The incidence of fatal pulmonary embolism after knee replacement with no prophylactic anticoagulation.  J Bone Joint Surg Br. 1993;  75 940-941
  • 46 Planes A, Vovhelle N, Mazas F et al.. Prevention of postoperative venous thrombosis: a randomised trial comparing unfractionated heparin and low molecular weight heparin in patients undergoing total hip replacement.  Thromb Haemost. 1988;  60 407-410
  • 47 Colwell C W, Spiro T E, Trowbridge A A et al.. Use of enoxaparin, a low-molecular-weight heparin, and unfractionated heparin for the prevention of deep vein thrombosis after elective hip replacement. A clinical trial comparing efficacy and safety.  J Bone Joint Surg Am. 1994;  76 3-14
  • 48 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;  119 1105-1112
  • 49 Leyvraz P F, Richard J, Bachmann F et al.. Adjusted versus fixed dose subcutaneous heparin in the prevention of deep vein thrombosis after total hip replacement.  N Engl J Med. 1983;  309 954-958
  • 50 Hull R D, Pineo G F, MacIsaac S. Low-molecular-weight heparin prophylaxis: pre-operative versus postoperative initiation in patients undergoing elective hip surgery.  Thromb Res. 2001;  101 155-162
  • 51 Eriksson B I, Lassen M R. for the PENTasacharide in Hip-FRActure Surgery Plus (PENTIPHRA 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 1337-1342
  • 52 Lassen M R, Borris L C, Anderson B S et al.. Efficacy and safety of prolonged thromboprophylaxis with a low molecular weight heparin (dalteparin) after total hip arthroplasty-the Danish Prolonged Prophylaxis (DaPP) study.  Thromb Res. 1998;  89 281-287
  • 53 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 randomised comparison of enoxaparin versus placebo.  Lancet. 1996;  348 224-228
  • 54 Bergqvist D, Benoni G, Björgell O et al.. Low-molecular-weight heparin (enoxaparin) as prophylaxis against venous thromboembolism after total hip replacement.  N Engl J Med. 1996;  335 696-700
  • 55 Dahl O E, Andreassen G, Aspelin T et al.. 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
  • 56 Prandoni P, Bruchi O, Sabbion P et al.. Prolonged thromboprophylaxis with oral anticoagulants after total hip arthroplasty: a prospective controlled randomized study.  Arch Intern Med. 2002;  162 1966-1971
  • 57 Comp P C, Spiro T E, Friedman R J et al.. Prolonged enoxaparin therapy to prevent venous thromboembolism after primary hip or knee replacement. Enoxaparin Clinical Trial Group.  J Bone Joint Surg Am. 2001;  83 336-345
  • 58 White R H, Romano P S, Zhou H, Rodrigo J, Bargar W. Incidence and time course of thromboembolic outcomes following total hip or knee arthroplasty.  Arch Intern Med. 1998;  158 1525-1531
  • 59 Hjelmstedt A, Bergvall U. Incidence of thrombosis in patients with tibial fractures: a phlebographic study.  Acta Chir Scand. 1968;  134 209-218
  • 60 Abelseth G, Buckley R E, Pineo G E, Hull R, Rose M S. Incidence of deep vein thrombosis in patients with fractures of the lower extremity distal to the hip.  J Orthop Trauma. 1996;  10 230-235
  • 61 Stringer M D, Steadman C A, Hedges A R, Thomas E M, Morley T R, Kakkar V V. Deep vein thrombosis after elective knee surgery. An incidence study in 312 patients.  J Bone Joint Surg Br. 1989;  71 492-497
  • 62 Kujath P, Spannagel U, Habscheid W. Incidence and prophylaxis of deep venous thrombosis in outpatients with injury of the lower limb.  Haemostasis. 1993;  23(suppl 1) 20-26
  • 63 Kock H J, Schmit-Neuerburg K P, Hanke J, Rudofsky G, Hirche H. Thromboprophylaxis with low-molecular-weight heparin in outpatients with plaster-cast immobilization of the leg.  Lancet. 1995;  346 459-461
  • 64 Lassen M R, Borris L C, Nakov R L. Use of the low-molecular-weight heparin reviparin to prevent deep vein thrombosis after leg injury requiring immobilization.  N Engl J Med. 2002;  347 726-730
  • 65 Jørgensen P S, Warming T, Hansen K et al.. Low molecular weight heparin (Innohep) as thromboprophylaxis in outpatients with a plaster cast: a venographic controlled study.  Thromb Res. 2002;  105 477-480
  • 66 Giannadakis K, Gehling H, Sitter H, Acherbach S, Hahne H, Gotzen L. Is a general pharmacological thromboembolism prophylaxis necessary in ambulatory treatment by plaster cast immobilization in lower limb injuries?.  Unfallchirurg. 2000;  103 475-478
  • 67 Solis G, Saxby T. Incidence of DVT following surgery of the foot and ankle.  Foot Ankle Int. 2002;  23 411-414
  • 68 Demers C, Marcoux S, Ginsberg J S, Laroche F, Cloutier R, Poulin J. Incidence of venographically proved deep vein thrombosis after knee arthroscopy.  Arch Intern Med. 1998;  158 47-50
  • 69 Schippinger G, Wirnsberger G H, Obernosterer A, Babinski K. Thromboembolic complications after arthroscopic knee surgery. Incidence and risk factors in 111 patients.  Acta Orthop Scand. 1998;  69 144-146
  • 70 Jaureguito J W, Greenwald A E, Wilcox J F, Paulos L E, Rosenberg T D. The incidence of deep venous thrombosis after arthroscopic knee surgery.  Am J Sports Med. 1999;  27 707-710
  • 71 Wirth T, Schneider B, Misselwitz F et al.. Prevention of venous thromboembolism after knee arthroscopy with low-molecular-weight heparin (reviparin): results of a randomised controlled trial.  Arthroscopy. 2001;  17 393-399
  • 72 Michot M, Conen D, Holtz D et al.. Prevention of deep-vein thrombosis in ambulatory arthroscopic knee surgery: a randomised trial of prophylaxis with low-molecular-weight heparin.  Arthroscopy. 2002;  18 257-263
  • 73 Belch J J, Lowe G D, Pollock J G, Forbes C D, Prentice C R. Low dose heparin in the prevention of deep-vein thrombosis after aortic bifurcation graft surgery.  Thromb Haemost. 1980;  42 1429-1433
  • 74 Olin J W, Graor R A, O'Hara P, Young J R. The incidence of deep venous thrombosis in patients undergoing abdominal aortic aneurysm resection.  J Vasc Surg. 1993;  18(6) 1037-1041
  • 75 Hollyoak M, Woodruff P, Muller M, Daunt N, Weir P. Deep venous thrombosis in postoperative vascular surgical patients: a frequent finding without prophylaxis.  J Vasc Surg. 2001;  34(4) 656-660
  • 76 Saarinen J, Sisto T, Laurikka J, Salenius J P, Tarkka M. Late sequelae of acute deep venous thrombosis: evaluation five and ten years after.  Phlebology. 1995;  10 106-109
  • 77 Farkas J C, Chapuis C, Combe S et al.. A randomised controlled trial of a low-molecular-weight heparin (Enoxaparin) to prevent deep-vein thrombosis in patients undergoing vascular surgery.  Eur J Vasc Surg. 1993;  7(5) 554-560
  • 78 Kudsk K A, Fabian T C, Baum S, Gold R E, Mangiante E, Voeller G. Silent deep vein thrombosis in immobilized multiple trauma patients.  Am J Surg. 1989;  158(6) 515-519
  • 79 Meissner M H, Chandler W L, Elliott J S. Venous thromboembolism in trauma: a local manifestation of systemic hypercoagulability?.  J Trauma. 2003;  54(2) 224-231
  • 80 Geerts W H, Jay R M, Code K I et al.. A comparison of low-dose heparin with low molecular weight heparin as prophylaxis against venous thromboembolism after major trauma.  N Engl J Med. 1996;  335 701-707
  • 81 Elliott C G, Dudney T M, Egger M et al.. Calf-thigh sequential pneumatic compression compared with plantar venous pneumatic compression to prevent deep-vein thrombosis after non-lower extremity trauma.  J Trauma. 1999;  47(1) 25-32
  • 82 Consortium for Spinal Cord Medicine . Prevention of thromboembolism in spinal cord injury.  J Spinal Cord Med. 1997;  20(3) 259-283
  • 83 Cade J F. High risk of the critically ill for venous thromboembolism.  Crit Care Med. 1982;  10(7) 448-450
  • 84 Belch J J, Lowe GDO, Ward A G, Forbes C D, Prentice CRM. Prevention of deep vein thrombosis in medical patients by low-dose heparin.  Scott Med J. 1981;  26 115-117
  • 85 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(11) 793-800
  • 86 Leizorovicz A, Cohen A T, Turpie A G, Olsson C G, Vaitkus P T, Goldhaber S Z. Randomized, placebo-controlled trial of dalteparin for the prevention of venous thromboembolism in acutely ill medical patients.  Circulation. 2004;  110(7) 874-879
  • 87 Cohen A T, Davidson B L, Gallus A S 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
  • 88 Nicolaides A N, Breddin H K, Fareed J et al.. Prevention of venous thromboembolism. International Consensus Statement.  Int Angiol. 2001;  20(1) 1-37
  • 89 Levine M, Rickles F R. Treatment of venous thromboembolism in cancer patients.  Haemostasis. 1998;  28(suppl 3) 66-70
  • 90 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(9) 963-968
  • 91 Samama M M. An epidemiologic study of risk factors for deep vein thrombosis in medical outpatients.  Arch Intern Med. 2000;  160 3415-3420
  • 92 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
  • 93 Baglin T P, White K, Charles A. Fatal pulmonary embolism in hospitalised medical patients.  J Clin Pathol. 1997;  50 609-610
  • 94 Goldhaber S Z, Tapson V F. A prospective registry of 5,451 patients with ultrasound-confirmed deep vein thrombosis.  Am J Cardiol. 2004;  93(2) 259-262
  • 95 Tapson V F, Decousus H, Piovella F, Zotz R B, Allegrone J, Anderson F A. A multinational observational cohort study in acutely ill medical patients of practices in prevention of venous thromboembolism: findings of the International Medical Prevention Registry on Venous Thromboembolism (IMPROVE).  Blood. 2003;  11 321a
  • 96 Halkin H, Goldberg J, Modan M, Modan B. Reduction of mortality in general medical in-patients by low-dose heparin prophylaxis.  Ann Intern Med. 1982;  96 561-565
  • 97 Gardlund B. Randomised, controlled trial of low-dose heparin for prevention of fatal pulmonary embolism in patients with infectious diseases.  Lancet. 1996;  347 1357-1361
  • 98 Lechler E, Schramm W, Flosbach C W. 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
  • 99 Kleber F X, Witt C, Vogel G, Koppenhagen K, Schomaker U, Flosbach C W. 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
  • 100 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 randomized clinical trials.  Thromb Haemost. 2000;  83 14-19
  • 101 Alikhan R. A safety analysis of thromboprophylaxis in acute medical illness.  Thromb Haemost. 2003;  89 590-591
  • 102 Lloyd A C, Anderson P M, Quinlan D J, Bearne A. Economic evaluation of the use of enoxaparin for thromboprophylaxis in acutely ill medical patients.  Journal of Medical Economics. 2001;  4 99-113
  • 103 McGarry L J, Thompson D, Weinstein M C, Goldhaber S Z. Cost effectiveness of thromboprophylaxis with a low-molecular-weight heparin versus unfractionated heparin in acutely ill medical inpatients.  Am J Manag Care. 2004;  10(9) 632-642
  • 104 Turpie AGG, Levine M N, Hirsh J 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(8532) 523-526
  • 105 Turpie AGG. Orgaran in the prevention of deep vein thrombosis in stroke patients.  Haemostasis. 1992;  22 92-98
  • 106 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
  • 107 Muir K W, Watt A, Baxter G, Grosset D G, Lees K R. Randomized trial of graded compression stockings for prevention of deep-vein thrombosis after acute stroke.  QJM. 2000;  93(6) 359-364
  • 108 Kapoor M, Kupfer Y Y, Tessler S. Subcutaneous heparin prophylaxis significantly reduces the incidence of venous thromboemolic events in the critically ill.  Crit Care Med. 1999;  27(12 suppl) A69
  • 109 Goldhaber S Z, Kett D H, Cusumano C J et al.. Low molecular weight heparin versus minidose unfractionated heparin for prophylaxis against venous thromboembolism in medical intensive care unit patients: a randomized controlled trial.  JACC. 2000;  35(suppl) 325A

Professor Mario PiniM.D. 

Medicina II, Ospedale di Fidenza

via Tencati 5, 43036 Fidenza, Parma, Italy

Email: mpini@ausl.pr.it

    >