Drugs

, Volume 60, Issue 3, pp 575–595 | Cite as

Proficient and Cost-Effective Approaches for the Prevention and Treatment of Venous Thrombosis and Thromboembolism

Review Article

Abstract

Thrombosis is clearly a common cause of death in the US. It is obviously of major importance to define the aetiology of deep vein thrombosis (DVT) as (i) many of these events are preventable if appropriate therapy, dependent upon the risk factors known is utilised; (ii) appropriate antithrombotic therapy will decrease risks of recurrence; (iii) the type of defect(s) and risk(s) will determine length of time the patient should remain on therapy for secondary prevention and (iv) if the defect is hereditary appropriate family members can be assessed. Aside from mortality, significant additional morbidity occurs from DVT including, but not limited to, stasis ulcers and other sequelae of post-phlebitic syndrome.

Numerous studies have provided evidence that medical patients and patients undergoing surgery or trauma are at significant risk for developing DVT, including pulmonary embolism (PE). Thus, an important task for the clinician is to prevent DVT and its complications. It is important to define risk groups where prophylaxis must be considered. The attitudes and beliefs towards prophylaxis show great regional variations. This is true for the definition of risk groups, the proportion of patients receiving prophylaxis and prophylactic modalities used. For this reason, various ‘consensus conference’ groups have attempted to alleviate these problems; the primary mission of consensus guidelines is to provide optimal direction to the clinician in the setting of clinical practice. If the practice guidelines generated are successful they will assist clinicians in decision-making for their patients, and they will also provide protection against unjustified malpractice actions.

Therapy may be complex, as clinical studies continue to identify more effective treatments. This review includes currently accepted approaches to the treatment of DVT. The clinical course of DVT is highly dynamic. When the response to therapy is not as expected, more than one cause of DVT may be present in a patient. Treatment must address the primary coagulopathy as well as any precipitating factors. The risk of pharmacological intervention must be balanced against potential benefit.

If the incidence of DVT in a given disorder is low and if the mortality rate is similarly low, therapy with an agent known to be associated with a high risk for complications, such as warfarin, would not be indicated. If DVT is seen primarily after surgery or in other high-risk situations, therapy might be limited to a fixed time period. However, if the ongoing risk of DVT remains high or if a history of recurrent DVT dictates, lifelong therapy might be indicated. The recommendations presented are based upon published controlled trials; however, indications for therapy and therapeutic agents of choice will continually evolve.

By applying the principles outlined in this review, substantial cost savings, reduction in morbidity and reductions in mortality should occur.

References

  1. 1.
    Bick RL, Fareed J. Current status of thrombosis: a multidisciplinary medical issue and major American health problem: beyond the year 2000. Clin Appl Thromb Hemost 1997; 3 Suppl.: 1Google Scholar
  2. 2.
    American Heart Association. Heart and stroke-1997. Dallas (TX): American Heart Association, 1996Google Scholar
  3. 3.
    Bick RL, Kaplan H. Syndromes of thrombosis and hypercoagulability: congenital and acquired causes of thrombosis. Med Clin North Am 1998; 82: 409–58PubMedCrossRefGoogle Scholar
  4. 4.
    Bick RL, Jakway J, Baker W.F. Deep vein thrombosis: prevalence of etiologic factors and results of management in 100 consecutive patients. Semin Thromb Hemost 1992; 18: 267–74PubMedCrossRefGoogle Scholar
  5. 5.
    Bergqvist D, Lundblad B. Incidence of venous thromboembolism in medical and surgical patients. In: Bergqvist D, Comerota A, Nicolaides A, et al., editors. Prevention of venous thromboembolism. London: Med-Orion Press, 1994: 3–16Google Scholar
  6. 6.
    Silverstein MD, Heit JA, Mohr DN, et al. Trends in the incidence of deep vein thrombosis and pulmonary embolism: a 25-year population-based study. Arch Intern Med 1998; 158(6): 585–93PubMedCrossRefGoogle Scholar
  7. 7.
    Ramaswami G, Nicolaides AN. The natural history of deep vein thrombosis [chapter 10]. In: Bergqvist D, Comerota A, Nicolaides A, et al., editors. Prevention of venous throinboembolism. London: Med-Orion Press, 1994: 3: 109–22Google Scholar
  8. 8.
    Bick RL, Ancypa D. Blood protein defects associated with thrombosis: laboratory assessment. Clin Lab Med 1995; 15(1): 125–63PubMedGoogle Scholar
  9. 9.
    MedPar. The MedStat group outcomes analysis. Nashville (TN): Medpar, 1998Google Scholar
  10. 10.
    De Stefano V, Finazzi G, Mannucci PM. Inherited thrombophilia: pathogenesis, clinical syndromes and management. Blood 1996; 87(9): 3531–44PubMedGoogle Scholar
  11. 11.
    Bick RL. Sticky platelet syndrome: a common cause of unexplained venous and arterial thrombosis-results of prevalence and treatment outcome. Clin Appl Thromb Hemost 1998; 4: 77–81CrossRefGoogle Scholar
  12. 12.
    Mammen EF. Ten year’s experience with the ‘Sticky Platelet Syndrome’. Clin Appl Thromb Hemost 1995; 1: 66–72CrossRefGoogle Scholar
  13. 13.
    Bick RL. The antiphospholipid thrombosis syndromes: a common multidisciplinary medical problem. Clin Appl Thromb Hemost 1997; 3: 270–83CrossRefGoogle Scholar
  14. 14.
    Bick RL. Antiphospholipid thrombosis syndromes: etiology, pathophysiology, diagnosis and management. Int J Hematol 1997; 65(3): 193–213PubMedCrossRefGoogle Scholar
  15. 15.
    Bick RL. Therapy for venous thrombosis: guidelines for a competent and cost-effective approach. Clin Appl Thromb Hemost 1999; 5: 2–9PubMedCrossRefGoogle Scholar
  16. 16.
    Bick RL, Hinton R.C. Prevalence of hereditary and acquired coagulation protein/platelet defects in patients with cerebral ischemic events [abstract]. Blood 1998; 92: Suppl. 1 (Pt 2): 114Google Scholar
  17. 17.
    Bick RL. Syndromes of thrombosis and hypercoagulability: congenital and acquired thrombophilias. Clin Appl Thromb Hemost 1989; 4: 25–50CrossRefGoogle Scholar
  18. 18.
    Beyth RJ, Cohen AM, Landefeld CS. Long-term outcomes of deep-vein thrombosis. Arch Intern Med 1995; 155(10): 1031–7PubMedCrossRefGoogle Scholar
  19. 19.
    Prandoni P, Lensing AWA, Cogo A, et al. The long-term clinical course of acute deep venous thrombosis. Ann Intern Med 1996; 125(1): 1–7PubMedGoogle Scholar
  20. 20.
    Marshall J, Tu D. Dalteparin: a low molecular weight heparin. PHD Pharm Lett 1998; 16: 1–3Google Scholar
  21. 21.
    Ardeparin and danaparoid for prevention of deep vein thrombosis. Med Lett Drugs Ther 1997; 39(1011): 94–5Google Scholar
  22. 22.
    Bick RL, Haas SK. International consensus recommendations: summary statement and additional suggested guidelines. Med Clin North Am 1998; 83: 613–34CrossRefGoogle Scholar
  23. 23.
    American College of Chest Physicians. Conference on anti-thrombotic therapy. Chest 1986 Feb; 89: 1–69Google Scholar
  24. 24.
    European Consensus Statement on the prevention of venous thromboembolism. Int Angiol 1992; 11: 151–9Google Scholar
  25. 25.
    Waersted A, Westbye O, Beermann B, et al., editors. Treatment of venous thrombosis and pulmonary embolism. In: Waersted A, Westbye O, Beermann B, et al., editors. Norwegian Medicines Control Authority, Oslo Norway, 1995. Sueden: Medical Products Agency Uppsala, 1995: 1–89Google Scholar
  26. 26.
    Prevention of venous thromboembolism. International Consensus Statement (guideline according to scientific evidence) [editorial]. Int Angiol 1997; 16: 3–77Google Scholar
  27. 27.
    Mclntyre K. Medicolegal implications of consensus statements. Chest 1995; 108: 502–5CrossRefGoogle Scholar
  28. 28.
    Hull RD, Pineo GF. Prophylaxis of deep venous thrombosis and pulmonary embolus: current recommendations. Med Clin North Am 1998; 82(3): 477–93PubMedCrossRefGoogle Scholar
  29. 29.
    Dismuke SE, Wagner EH. Pulmonary embolism as a cause of death: the changing mortality in hospitalized patients. JAMA 1986; 255(15): 2039–42PubMedCrossRefGoogle Scholar
  30. 30.
    Dalen JE, Alpert JS. Natural history of pulmonary embolism. Prog Cardiovasc Dis 1975; 17(4): 257–70CrossRefGoogle Scholar
  31. 31.
    Baker WF. Diagnosis of deep venous thrombosis and pulmonary emboism. Med Clin North Am 1998; 82(3): 459–76PubMedCrossRefGoogle Scholar
  32. 32.
    Anderson 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(5): 933–8CrossRefGoogle Scholar
  33. 33.
    Clagett GP, Reisch JS. Prevention of venous thromboembolism in general surgical patients: results of meta-analysis. Ann Surg 1988; 208(2): 227–40PubMedCrossRefGoogle Scholar
  34. 34.
    Collins R, Scrimgeour A, Yusef S, et al. Reduction in fatal pulmonary embolism and venous thrombosis by perioperative administration of subcutaneous heparin. N Engl J Med 1988; 318: 1162–73PubMedCrossRefGoogle Scholar
  35. 35.
    Nicolaides AN, Bergqvist D, Hull RD, et al. Prevention of venous thromboembolism: International Consensus Statement. Int Angiol 1997; 16:3–38Google Scholar
  36. 36.
    Nicolaides AN. Prevention of thromboembolism: European Consensus Statement. In: Bergqvist D, Comerota AJ, Nicolaides AN, et al., editors. Prevention of venous thromboembolism. Los Angeles: Med-Orion Publishing Co., 1994: 443–56Google Scholar
  37. 37.
    Bratzler DW, Raskob GE, Murray CK, et al. Underuse of venous thromboembolism prophylaxis for general surgery patients. Arch Intern Med 1998; 158(17): 1909–12PubMedCrossRefGoogle Scholar
  38. 38.
    Kakkar VV, Adams PC. Preventive and therapeutic approach to venous thromboembolism: can death from pulmonary embolism be prevented? J Am Coll Cardiol 1986; 8: 146B–58PubMedCrossRefGoogle Scholar
  39. 39.
    Skinner DB, Salzman EW. Anticoagulant prophylaxis in surgical patients. Surg Gynecol Obstet 1967; 125(4): 741–6PubMedGoogle Scholar
  40. 40.
    Shephard RM, White HA, Shirkey AL. Anticoagulant prophylaxis of thromboembolism in post-surgical patients. Am J Surg 1966; 112:698–702CrossRefGoogle Scholar
  41. 41.
    International Multicentre Trial: prevention of fatal postoperative pulmonary embolism by low doses of heparin. Lancet 1975; II: 45–64Google Scholar
  42. 42.
    Bergqvist D. Prevention in individual patient groups: general surgery. In: Bergqvist D, Comerota AJ, Nicolaides AN, et al., editors. Prevention of venous thromboembolism. Los Angeles: Med-Orion Publishing Co, 1994: 243–8Google Scholar
  43. 43.
    Coventry MB, Nolan DR, Beckenbaugh RD. ‘Delayed’ prophylactic anticoagulation: a study of results and complications in 2,012 total hip arthroplasties. J Bone Joint Surg Am 1973; 55(7): 1487–92PubMedGoogle Scholar
  44. 44.
    Eskeland G, Solheim K, Skhorten F. Anticoagulant prophylaxis, thromboembolism and mortality in elderly patients with hip fracture: a controlled clinical trial. Acta Chir Scand 1986; 131: 16–29Google Scholar
  45. 45.
    Kearon C, Hirsh J. Starting prophylaxis for venous thromboembolism postoperatively. Arch Intern Med 1995; 155(4): 366–72PubMedCrossRefGoogle Scholar
  46. 46.
    Palareti G, Borghi B, Coccheri S, for the CITO Study Group. Postoperative versus preoperative initiation of deep-vein thrombosis prophylaxis with a low molecular weight heparin (Nadroparin) in elective hip replacement. Clin Appl Thromb Hemost 1996; 2: 18–24CrossRefGoogle Scholar
  47. 47.
    Hull RD, Hirsh J, Carter CJ, et al. Diagnostic efficacy of impedance plethysmography for clinically suspected deep-vein thrombosis: a randomized trial. Ann Intern Med 1985; 102(1): 21–8PubMedGoogle Scholar
  48. 48.
    Walenga J, Bick RL. Heparin associated thrombocytopenia and other adverse effects of heparin therapy. Cardiol Clin (Ann Drug Ther) 1998; 2: 123–40Google Scholar
  49. 49.
    Kakkar VV, Cohen AT, Edmonson RA, et al. Low molecular weight versus standard heparin for prevention of venous thromboembolism after major abdominal surgery: the Thrombo-prophylaxis Collaborative Group. Lancet 1993; 341(8840): 259–65PubMedCrossRefGoogle Scholar
  50. 50.
    Kakkar VV, Boeckl O, Boneau B, et al. Efficacy and safety of a low-molecular-weight heparin and standard unfractionated heparin for prophylaxis of postoperative venous thromboembolism: European multicenter trial. World J Surg 1997; 21(1): 2–8PubMedCrossRefGoogle Scholar
  51. 51.
    Bergqvist D, Matzsch T, Brumark U, et al. Low-molecular-weight heparin given the evening before surgery compared with conventional low-dose heparin in prevention of thrombosis. Br J Surg 1988; 75(9): 888–91PubMedCrossRefGoogle Scholar
  52. 52.
    Samama M, Bernard P, Bonnardot JP, et al. Low-molecular-weight heparin compared with unfractionated heparin in prevention of postoperative thrombosis. Br J Surg 1988; 75(2): 128–31PubMedCrossRefGoogle Scholar
  53. 53.
    European Fraxiparin Study Group. Comparison of a low-molecular-weight heparin and unfractionated heparin for the prevention of deep vein thrombosis in patients undergoing abdominal surgery. Br J Surg 1988; 75: 1058–63CrossRefGoogle Scholar
  54. 54.
    Caen JP. A randomized double-blind study between a low-molecular-weight heparin Kabi 2165 and standard heparin in the prevention of deep-vein thrombosis in general surgery: a French multicentre trial. Thromb Haemost 1988; 59(2): 216–20PubMedGoogle Scholar
  55. 55.
    Leizorovicz A, Picolet H, Peyrieux JC, et al. Prevention of perioperative deep vein thrombosis in general surgery: a multi-centre double-blind study comparing two doses of logiparin and standard heparin. Br J Surg 1991; 78: 412–16CrossRefGoogle Scholar
  56. 56.
    Nurmohamed MT, Verhaeghe R, Haas S, et al. A comparative trial of a low molecular weight heparin (Enoxaparin) versus standard heparin for the prophylaxis of postoperative deep vein thrombosis in general surgery. Am J Surg 1995; 169(6): 567–71PubMedCrossRefGoogle Scholar
  57. 57.
    Bergqvist D, Burmark US, Flordal PA, et al. Low molecular weight heparin started before surgery as prophylaxis against deep vein thrombosis: 2500 versus 500 Xal units in 2070 patients. Br J Surg 1995; 82(4): 496–501PubMedCrossRefGoogle Scholar
  58. 58.
    Leclerc JR, Geerts WH, Desjardins L, et al. Prevention of deep vein thrombosis after major knee surgery: a randomized, double-blind trial comparing a low-molecular-weight heparin fragment (Enoxaparin) to placebo. Thromb Haemost 1992; 67(4): 417–23PubMedGoogle Scholar
  59. 59.
    Leclerc JR, Geerts WH, Desjardins L, et al. Prevention of venous thromboembolism after knee arthroplasty — a randomized, double-blind trial comparing a low molecular weight heparin fragment (Enoxparin) to Warfarin [abstract]. Thromb Haemost 1995; 73(6): 1103Google Scholar
  60. 60.
    Heit J, Berkowitz S, Bona R, et al. Efficacy and safety of Normiflow (a LMWH) compared to warfarin for prevention of venous thromboembolism following total knee replacement: a double-blind, dose-ranging study [abstract]. Thromb Haemost 1995; 73(6): A739Google Scholar
  61. 61.
    Nurmohamed MT, Rosendaal FR, Büller HR, et al. Low molecular weight heparin in the prophylaxis of venous thrombosis: a meta-analysis. Lancet 1992; 340: 152–6PubMedCrossRefGoogle Scholar
  62. 62.
    Geerts WH, Jay RM, Code Kl, 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(10): 701–7PubMedCrossRefGoogle Scholar
  63. 63.
    Dale C, Gallus A, Wycherley A, et al. Prevention of venous thrombosis with minidose warfarin after joint replacement. BMJ 1991; 303(6796): 224PubMedCrossRefGoogle Scholar
  64. 64.
    Roberts VC, Sabri S, Beely AH, et al. The effect of intermittently applied external pressure on the hemodynamics of the lower limb in man. Br J Surg 1972; 59(3): 233–6CrossRefGoogle Scholar
  65. 65.
    Skillman JJ, Collins RR, Coe NP, et al. Prevention of deep vein thrombosis in neurosurgical patients: a controlled, randomized trial of external pneumatic compression boots. Surgery 1978; 83(3): 354–8PubMedGoogle Scholar
  66. 66.
    Ramos R, Salem BI, Pawlikowski MP, et al. The efficacy of pneumatic compression stockings in the prevention of pulmonary embolism after cardiac surgery. Chest 1996; 109(1): 82–5PubMedCrossRefGoogle Scholar
  67. 67.
    Hull RD, Raskob G, Gent M, et al. Effectiveness of intermittent pneumatic leg compression for preventing deep vein thrombosis after total hip replacement. JAMA 1990; 263(17): 2313–7PubMedCrossRefGoogle Scholar
  68. 68.
    Clagett GP, Anderson FA, Heit J. Prevention of venous thromboembolism. Chest 1998; 114 (5 Suppl.): 531S–60PubMedCrossRefGoogle Scholar
  69. 69.
    Turner GM, Cole SF, Brooks JH. The efficacy of graduated compression stockings in the prevention of deep vein thrombosis after major gynecological surgery. Br J Obstet Gynecol 1984; 91: 588–91CrossRefGoogle Scholar
  70. 70.
    Kakkar VV. Effectiveness and safety of low molecular weight heparins (LMWH) in the prevention of venous thromboembolism. Thromb Haemost 1995; 74(1): 364–8PubMedGoogle Scholar
  71. 71.
    Haas SK. Treatment of deep venous thrombosis: current recommendations. Med Clin North Am 1998; 82(3): 495–510PubMedCrossRefGoogle Scholar
  72. 72.
    Philbrick JT, Becker DM. Calf deep vein thrombosis: a wolf in sheep’s clothing. Arch Intern Med 1988; 148(10): 2131–8PubMedCrossRefGoogle Scholar
  73. 73.
    Baker WF, Bick RL. Deep vein thrombosis: diagnosis and management. Med Clin North Am 1994; 78(3): 685–712PubMedGoogle Scholar
  74. 74.
    Murano G, Bell WR. Thrombolytic therapy. In: Bick RL, Bennett JM, Brynes RK, editors. Hematology: clinical and laboratory practice. St Louis (MO): Mosby, 1993: 1624–33Google Scholar
  75. 75.
    Bell WR. Thrombolytic therapy: agents, indications and laboratory monitoring. Med Clin North Am 1994; 78(3): 745–64PubMedGoogle Scholar
  76. 76.
    Hoomes DW, Bura A, Mazzolai L, et al. Subcutaneous heparin compared with continuous intravenous heparin administration in the initial treatment of deep vein thrombosis: a meta-analysis. Ann Intern Med 1992; 116: 279–84Google Scholar
  77. 77.
    Doyle DJ, Turpie AGG, Hirsh J, et al. Adjusted subcutaneous heparin or continuous intravenous heparin in patients with acute deep vein thrombosis. Ann Intern Med 1987; 107(4): 441–5PubMedGoogle Scholar
  78. 78.
    Anderson G, Fagrell B, Holmgren K, et al. Subcutaneous administration of heparin: a randomized comparison with intravenous administration of heparin to patients with deep-vein thrombosis. Thromb Res 1982; 27: 631–9CrossRefGoogle Scholar
  79. 79.
    Hull RD, Raskob G, Hirsh J, et al. Continuous intravenous heparin compared with intermittent subcutaneous heparin in the initial treatment of proximal vein thrombosis. N Engl J Med 1986; 315(18): 1109–14PubMedCrossRefGoogle Scholar
  80. 80.
    Hull RD, Raskob GE, Brant RF, et al. The importance of initial treatment on long-term outcomes of antithrombotic therapy. Arch Intern Med 1997; 157(20): 2317–21PubMedCrossRefGoogle Scholar
  81. 81.
    Walenga JM, Bick RL. Heparin-induced thrombocytopenia, paradoxical thromboembolism, and other side effects of heparin therapy. Med Clin North Am 1998; 82(3): 635–58PubMedCrossRefGoogle Scholar
  82. 82.
    Columbus Investigators. Low-molecular-weight heparin in the treatment of patients with venous thromboembolism. N Engl J Med 1997; 337: 657–62CrossRefGoogle Scholar
  83. 83.
    Duroux P. A Collaborative European Multicentre Study: a randomized trial of subcutaneous low molecular weight heparin (CY216) compared with intravenous unfractionated heparin in the treatment of deep vein thrombosis. Thromb Haemost 1991; 65: 251–6Google Scholar
  84. 84.
    Faivre R, Neuhart Y, Kieffer Y, et al. A new treatment of deep venous thrombosis: low molecular weight heparin fractions: randomized study [in French]. Presse Med 1988; 17(5): 197–200PubMedGoogle Scholar
  85. 85.
    Fiessinger JN, Lopez-Fernandez M, Gatterer E, et al. Once-daily subcutaneous Dalteparin, a low molecular weight heparin, for the initial treatment of acute deep vein thrombosis. Thromb Haemost 1996; 76(2): 195–9PubMedGoogle Scholar
  86. 86.
    Hull RD, Raskob GE, Pineo GF, et al. Subcutaneous low-molecular-weight heparin compared with continuous intravenous heparin in the treatment of proximal-vein thrombosis. N Engl J Med 1992; 326(15): 975–82PubMedCrossRefGoogle Scholar
  87. 87.
    Koopman MM, Prandoni P, Piovella F, et al. Treatment of venous thrombosis with intravenous unfractionated heparin administered in the hospital as compared with subcutaneous low-molecular-weight heparin administered at home. N Engl J Med 1996; 334(11): 682–7PubMedCrossRefGoogle Scholar
  88. 88.
    Levine M, Gent M, Hirsh J, et al. A comparison of low-molecular-weight heparin administered primarily at home with unfractionated heparin administered in the hospital for proximal deep-vein thrombosis. N Engl J Med 1996; 334: 677PubMedCrossRefGoogle Scholar
  89. 89.
    Lindmarker P, Holmstrom M, Granqvist S, et al. Comparison of once-daily subcutaneous Fragmin with continuous intravenous unfractionated heparin in the treatment of deep venous thrombosis. Thromb Haemost 1994; 72(2): 186–90PubMedGoogle Scholar
  90. 90.
    Lopaciuk S, Meissner AJ, Filipecki S, et al. Subcutaneous low molecular weight heparin versus subcutaneous unfractionated heparin in the treatment of deep vein thrombosis: a Polish multicenter trial. Thromb Haemost 1992; 68(1): 14–8PubMedGoogle Scholar
  91. 91.
    Luomanmaki K and the Finnish multicentre group. Low molecular weight heparin (Fragmin) once daily vs continuous infusion of standard heparin in the treatment of DVT [abstract]. Haemostasis 1994; 24 Suppl. 1: 248Google Scholar
  92. 92.
    Prandoni P, Lensing AWA, Buller HR, et al. Comparison of subcutaneous low-molecular-weight heparin with intravenous standard heparin in proximal deep-vein thrombosis. Lancet 1992; 339(8791): 441–5PubMedCrossRefGoogle Scholar
  93. 93.
    Simonneau G, Charbonnier B, Decousus H, et al. Subcutaneous low molecular weight heparin compared with continuous intravenous unfractionated heparin in the initial treatment proximal vein thrombosis. Arch Intern Med 1993; 153(13): 1541–6PubMedCrossRefGoogle Scholar
  94. 94.
    Simonneau G, Sors H, Charbonnier B, et al. A comparison of low-molecular-weight heparin with unfractionated heparin for acute pulmonary embolism: the THESEE Study Group. N Engl J Med 1997; 337(10): 663–9PubMedCrossRefGoogle Scholar
  95. 95.
    van den Belt AGM, Prins MH, Lensing AWA, et al. Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for venous thromboembolism. Cochrane Review. In: The Cochrane Library, Issue 2. Oxford: Update Software, 1998Google Scholar
  96. 96.
    Hull RD, Raskob GE, Pineo GF, et al. The treatment of proximal vein thrombosis with subcutaneous low molecular weight heparin compared with continuous intravenous heparin: the Canadian-American Thrombosis Study Group. Clin Appl Thromb Hemost 1995; 1: 151–9CrossRefGoogle Scholar
  97. 97.
    Shafer AI. Low-molecular-weight heparin: an opportunity for home treatment of venous thrombosis [editorial]. N Engl J Med 1996; 334: 724CrossRefGoogle Scholar
  98. 98.
    Harrison L, McGinnis J, Crowther M, et al. Assessment of outpatient treatment of deep-vein thrombosis with low-molecular-weight heparin. Arch Intern Med 1998; 158: 2001–3PubMedCrossRefGoogle Scholar
  99. 99.
    Wells P, Kovacs M, Bormanis J, et al. Expanding eligibility for outpatient treatment of deep venous thrombosis and pulmonary embolus with low-molecular-weight heparin: a comparison of self-injection with homecare injection. Arch Intern Med 1998; 158(16): 1809–12PubMedCrossRefGoogle Scholar

Copyright information

© Adis International Limited 2000

Authors and Affiliations

  1. 1.Department of Medicine and PathologyUniversity of Texas Southwestern Medical CenterDallasUSA
  2. 2.Dallas Thrombosis, Hemostasis and Difficult Hematology Clinical CenterDallasUSA

Personalised recommendations