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Semin Thromb Hemost 2002; 28(6): 569-576
DOI: 10.1055/s-2002-36701
Copyright © 2002 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Thromboembolic Disease In Surgery For Malignancy-Rationale For Prolonged Thromboprophylaxis

Amjad Khushal1 , Dan  Quinlan2 , Raza Alikhan1 , Jeremy Gardner1 , Clare  Bailey1 , Ander Cohen1
  • 1Department of Academic Surgery, Guy's, King's, and St. Thomas' Schools of Medicine, London
  • 2Radiology Department, King's College Hospital, London, United Kingdom
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Publication History

Publication Date:
21 January 2003 (online)

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ABSTRACT

Patients undergoing surgery for malignancy are at increased risk of initial and recurrent venous thromboembolism (VTE). Several factors have been found to increase the risk of deep vein thrombosis (DVT) in cancer patients both during the first days after the operation and after discharge from hospital. Although, in general, thromboprophylaxis is provided to cancer patients after surgery, the length of time these patients require prophylaxis has not yet been established. Autopsy series, clinical series, and clinical trials indicate that up to about 40% of VTE occurs post discharge. General surgical patients undergoing major abdominal surgery require VTE prophylaxis, and prolonged thromboprophylaxis should be considered in the post-discharge period in high-risk patients, particularly those with cancer. Evidence from studies in general and orthopedic surgery show that prolonged prophylaxis reduces the number of thromboembolic events after discharge from hospital. Prophylaxis should be simple, safe, and effective and should be administered easily to allow continuation of therapy after discharge. Low-molecular-weight heparins are potentially the most suitable agents for long-term thromboprophylaxis in cancer patients.

KEYWORD

Thromboprophylaxis - deep-vein thrombosis - pulmonary embolism - low-molecular-weight heparin (LMWH) - cancer surgery

REFERENCES

  • 1 Geerts W H, Heit J A, Clagett G P. Prevention of venous thromboembolism.  Chest . 2001;  119 132S-175S
    CrossrefPubMedSearch in Google Scholar
  • 2 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
    CrossrefPubMedSearch in Google Scholar
  • 3 Nicolaides A N, Bergqvist D, Hull R. Prevention of venous thromboembolism. International Consensus Statement (guidelines according to scientific evidence).  Int Angiol . 1997;  16 3-38
    PubMedSearch in Google Scholar
  • 4 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
    PubMedSearch in Google Scholar
  • 5 Rasmussen M S, Wille-Jørgensen P, Jørgensen L N. Postoperative fatal pulmonary embolism in a general surgical department.  Am J Surg . 1995;  169 214-216
    CrossrefPubMedSearch in Google Scholar
  • 6 Huber O, Bounameaux H, Borst F, Rohner A. Postoperative pulmonary embolism after hospital discharge. An underestimated risk.  Arch Surg . 1992;  127 310-313
    CrossrefPubMedSearch in Google Scholar
  • 7 Robinson K S, Anderson D R, Gross M. Ultrasonographic screening before hospital discharge for deep venous thrombosis after arthroplasty: the post-arthroplasty screening study. A randomized, controlled trial.  Ann Intern Med . 1997;  127 439-445
    PubMedSearch in Google Scholar
  • 8 Planes A, Vochelle N, Darmon J 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
    CrossrefPubMedSearch in Google Scholar
  • 9 Bergqvist D, Benoni G, Björgell O. Low-molecular-weight heparin (enoxaparin) as prophylaxis against venous thromboembolism after total hip replacement.  N Engl J Med . 1996;  335 696-700
    CrossrefPubMedSearch in Google Scholar
  • 10 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
    PubMedSearch in Google Scholar
  • 11 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 (DaPP) Study.  Thromb Res . 1998;  89 281-287
    CrossrefPubMedSearch in Google Scholar
  • 12 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, randomized comparison. North American Fragmin Trial Investigators.  Arch Intern Med . 2000;  160 2208-2215
    CrossrefPubMedSearch in Google Scholar
  • 13 Heit J A, Elliott C G, Trowbridge A A. Ardeparin sodium for extended out-of-hospital prophylaxis against venous thromboembolism after total hip or knee replacement. A randomized, double-blind, placebo-controlled trial.  Ann Intern Med . 2000;  132 853-861
    PubMedSearch in Google Scholar
  • 14 Lausen I, Jensen R, Jørgensen L N. Incidence and prevention of deep venous thrombosis occurring late after general surgery: randomised controlled study of prolonged thromboprophylaxis.  Eur J Surg . 1998;  164 657-663
    CrossrefPubMedSearch in Google Scholar
  • 15 Bergqvist D, Agnelli G, Cohen A T. Duration of prophylaxis against venous thromboembolism with enoxaparin after surgery for cancer.  N Engl J Med . 2002;  346 975-980
    CrossrefPubMedSearch in Google Scholar
  • 16 Donati M B. Cancer and thrombosis.  Haemostasis . 1994;  24 128-131
    PubMedSearch in Google Scholar
  • 17 Sproul E E. Carcinoma and venous thrombosis: the frequency of association of carcinoma in the body or tail of the pancreas with multiple venous thrombosis.  Am J Cancer . 1938;  34 566-585
    PubMedSearch in Google Scholar
  • 18 Ambrus J L, Ambrus C M, Pickern J, Soldes S, Bross I. Hematologic changes and thromboembolic complications in neoplastic disease and their relationship to metastasis.  J Med . 1975;  6 433-458
    PubMedSearch in Google Scholar
  • 19 Kakkar A K, Williamson R C. Prevention of venous thromboembolism in cancer patients.  Semin Thromb Hemost . 1999;  25 239-243
    Thieme ConnectPubMedSearch in Google Scholar
  • 20 Carson J L, Kelley M A, Duff A. The clinical course of pulmonary embolism.  N Engl J Med . 1992;  326 1240-1245
    CrossrefPubMedSearch in Google Scholar
  • 21 Gore J M, Appelbaum J S, Greene H L, Dexter L, Dalen J E. Occult cancer in patients with acute pulmonary embolism.  Ann Intern Med . 1982;  96 556-560
    PubMedSearch in Google Scholar
  • 22 Prandoni P, Lensing A W, Büller H R. Deep-vein thrombosis and the incidence of subsequent symptomatic cancer.  N Engl J Med . 1992;  327 1128-1133
    CrossrefPubMedSearch in Google Scholar
  • 23 Griffin M R, Stanson A W, Brown M L. Deep venous thrombosis and pulmonary embolism. Risk of subsequent malignant neoplasms.  Arch Intern Med . 1987;  147 1907-1911
    CrossrefPubMedSearch in Google Scholar
  • 24 Nordström M, Lindblad B, Anderson H, Bergqvist D, Kjellström T. Deep venous thrombosis and occult malignancy: an epidemiological study.  BMJ . 1994;  308 891-894
    CrossrefPubMedSearch in Google Scholar
  • 25 Baron J A, Gridley G, Weiderpass E, Nyren O, Linet M. Venous thromboembolism and cancer.  Lancet . 1998;  351 1077-1080
    CrossrefPubMedSearch in Google Scholar
  • 26 Sørensen H T, Mellemkjaer L, Steffensen F H, Olsen J H, Nielsen G L. The risk of a diagnosis of cancer after primary deep venous thrombosis or pulmonary embolism.  N Engl J Med . 1998;  338 1169-1173
    CrossrefPubMedSearch in Google Scholar
  • 27 Goldberg R J, Seneff M, Gore J M. Occult malignant neoplasm in patients with deep venous thrombosis.  Arch Intern Med . 1987;  147 251-253
    CrossrefPubMedSearch in Google Scholar
  • 28 Trousseau A. Lectures on Clinical Medicine.  London: The New Syndenham Society 1872: 282-332
    Search in Google Scholar
  • 29 Virchow R. Phlogose und Thrombose im GefäBsystem. In: Virchow R, ed. Gesammelte Abhandlungen zur Wissenschaftlichen Medicin Frankfurt, Germany: von Meidinger Sohn 1856: 458
    Search in Google Scholar
  • 30 Moore Jr D F, Osteen R T, Karp D D, Steele Jr G, Wilson R E. Anticoagulants, venous thromboembolism, and the cancer patient.  Arch Surg . 1981;  116 405-407
    PubMedSearch in Google Scholar
  • 31 Levine M N, Gent M, Hirsh J. The thrombogenic effect of anticancer drug therapy in women with stage II breast cancer.  N Engl J Med . 1988;  318 404-407
    CrossrefPubMedSearch in Google Scholar
  • 32 Ogawa S, Gerlach H, Esposito C. Hypoxia modulates the barrier and coagulant function of cultured bovine endothelium. Increased monolayer permeability and induction of procoagulant properties.  J Clin Invest . 1990;  85 1090-1098
    CrossrefPubMedSearch in Google Scholar
  • 33 Patterson W P, Ringenberg Q S. The pathophysiology of thrombosis in cancer.  Semin Oncol . 1990;  17 140-146
    PubMedSearch in Google Scholar
  • 34 Rickles F R, Edwards R L. Activation of blood coagulation in cancer: Trousseau's syndrome revisited.  Blood . 1983;  62 14-31
    PubMedSearch in Google Scholar
  • 35 Booth B W, Weiss R B. Venous thrombosis during adjuvant chemotherapy (Letter).  N Engl J Med . 1981;  305 170
    PubMedSearch in Google Scholar
  • 36 Weiss R B, Tormey D C, Holland J F, Weinberg V E. Venous thrombosis during multimodal treatment of primary breast carcinoma.  Cancer Treat Rep . 1981;  65 677-679
    PubMedSearch in Google Scholar
  • 37 Goodnough L T, Saito H, Manni A, Jones P K, Pearson O H. Increased incidence of thromboembolism in stage IV breast cancer patients treated with a five-drug chemotherapy regimen. A study of 159 patients.  Cancer . 1984;  54 1264-1268
    CrossrefPubMedSearch in Google Scholar
  • 38 Donati M B, Semeraro N. Cancer cell procoagulants and their pharmacological modulation.  Haemostasis . 1984;  14 422-429
    PubMedSearch in Google Scholar
  • 39 Reich R, Thompson E W, Iwamoto Y. Effects of inhibitors of plasminogen activator, serine proteinases, and collagenase IV on the invasion of basement membranes by metastatic cells.  Cancer Res . 1988;  48 3307-3312
    PubMedSearch in Google Scholar
  • 40 Carty N J, Taylor I, Roath O S, el-Baruni K, Francis J L. Tissue procoagulant activity may be important in sustaining metastatic tumour growth.  Clin Exp Metastasis . 1992;  10 175-181
    CrossrefPubMedSearch in Google Scholar
  • 41 Bergqvist D, Lindblad B. A 30-year survey of pulmonary embolism verified at autopsy: an analysis of 1274 surgical patients.  Br J Surg . 1985;  72 105-108
    PubMedSearch in Google Scholar
  • 42 Lindblad B, Eriksson A, Bergqvist D. Autopsy-verified pulmonary embolism in a surgical department: analysis of the period from 1951 to 1988.  Br J Surg . 1991;  78 849-852
    CrossrefPubMedSearch in Google Scholar
  • 43 Clarke-Pearson D L, Jelovsek F R, Creasman W T. Thromboembolism complicating surgery for cervical and uterine malignancy: incidence, risk factors, and prophylaxis.  Obstet Gynecol . 1983;  61 87-94
    PubMedSearch in Google Scholar
  • 44 Clarke-Pearson D L, Synan I S, Coleman R E, Hinshaw W, Creasman W T. The natural history of postoperative venous thromboemboli in gynecologic oncology: a prospective study of 382 patients.  Am J Obstet Gynecol . 1984;  148 1051-1054
    PubMedSearch in Google Scholar
  • 45 Sørensen C, Andersen M, Kristiansen V B, Jensen R, Wille-Jørgensen P. The occurrence of late thromboembolic complications after elective abdominal surgery [in Danish].  Ugeskr Laeger . 1990;  152 1586-1587
    PubMedSearch in Google Scholar
  • 46 Scurr J H, Coleridge-Smith P D, Hasty J H. Deep venous thrombosis: a continuing problem.  BMJ . 1988;  297 28
    PubMedSearch in Google Scholar
  • 47 Kakkar V V, Corrigan T P, Fossard D P. Prevention of fatal postoperative pulmonary embolism by low doses of heparin. An international multicentre trial.  Lancet . 1975;  2 45-51
    PubMedSearch in Google Scholar
  • 48 Kiil J, Kiil J, Axelsen F, Andersen D. Prophylaxis against postoperative pulmonary embolism and deep-vein thrombosis by low-dose heparin.  Lancet . 1978;  1 1115-1116
    PubMedSearch in Google Scholar
  • 49 Clarke-Pearson D L, Coleman R E, Synan I S, Hinshaw W, Creasman W T. Venous thromboembolism prophylaxis in gynecologic oncology: a prospective, controlled trial of low-dose heparin.  Am J Obstet Gynecol . 1983;  145 606-613
    PubMedSearch in Google Scholar
  • 50 Wille-Jørgensen P, Kjaergaard J, Thorup J. Heparin with and without dihydroergotamine in prevention of thromboembolic complications of major abdominal surgery. A randomized trial.  Arch Surg . 1983;  118 926-928
    PubMedSearch in Google Scholar
  • 51 Clarke-Pearson D L, Synan I S, Hinshaw W M, Coleman R E, Creasman W T. Prevention of postoperative venous thromboembolism by external pneumatic calf compression in patients with gynecologic malignancy.  Obstet Gynecol . 1984;  63 92-98
    PubMedSearch in Google Scholar
  • 52 Bergqvist D, Lindblad B. The thromboprophylactic effect of graded elastic compression stockings in combination with dextran 70.  Arch Surg . 1984;  119 1329-1331
    PubMedSearch in Google Scholar
  • 53 Wille-Jørgensen P, Thorup J, Fischer A, Holst-Christensen J, Flamsholt R. Heparin with and without graded compression stockings in the prevention of thromboembolic complications of major abdominal surgery: a randomized trial.  Br J Surg . 1985;  72 579-581
    PubMedSearch in Google Scholar
  • 54 Ockelford P A, Patterson J, Johns A S. A double-blind randomized placebo controlled trial of thromboprophylaxis in major elective general surgery using once daily injections of a low molecular weight heparin fragment (Fragmin).  Thromb Haemost . 1989;  62 1046-1049
    PubMedSearch in Google Scholar
  • 55 Leizorovicz A, Picolet H, Peyrieux J C, Boissel J P. Prevention of perioperative deep vein thrombosis in general surgery: a multicentre double blind study comparing two doses of logiparin and standard heparin. HBPM Research Group.  Br J Surg . 1991;  78 412-416
    PubMedSearch in Google Scholar
  • 56 Wille-Jørgensen P, Hauch O, Dimo B. Prophylaxis of deep venous thrombosis after acute abdominal operation.  Surg Gynecol Obstet . 1991;  172 44-48
    PubMedSearch in Google Scholar
  • 57 Kakkar V V, Cohen A T, Edmonson R A. Low molecular weight versus standard heparin for prevention of venous thromboembolism after major abdominal surgery. The Thromboprophylaxis Collaborative Group.  Lancet . 1993;  341 259-265
    CrossrefPubMedSearch in Google Scholar
  • 58 Collins R, Scrimgeour A, Yusuf S, Phil D, 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
    CrossrefPubMedSearch in Google Scholar
  • 59 Skinner J A, Gerrard D J, Zahn H. An assessment of deep venous function following total hip arthroplasty complicated by venographically proven deep vein thrombosis.  Thromb Haemost . 1995;  73 1110
    PubMedSearch in Google Scholar
  • 60 Prandoni P, Lensing A W, Cogo A. The long-term clinical course of acute deep venous thrombosis.  Ann Intern Med . 1996;  125 1-7
    CrossrefPubMedSearch in Google Scholar
  • 61 Andersen M, Wille-Jørgensen P. Late complications of asymptomatic deep venous thrombosis.  Eur J Surg . 1991;  157 527-530
    PubMedSearch in Google Scholar
  • 62 Cohen A T, Khushal A. Extended thromboprophylaxis following lower limb arthroplasty: what do the clinical trials mean?.  Haemostasis . 2000;  30 88-94
    CrossrefPubMedSearch in Google Scholar
  • 63 Mohr D N, Silverstein M D, Murtaugh P A, Harrison J M. Prophylactic agents for venous thrombosis in elective hip surgery. Meta-analysis of studies using venographic assessment.  Arch Intern Med . 1993;  153 2221-2228
    CrossrefPubMedSearch in Google Scholar
  • 64 Lieberman J R, Wollaeger J, Dorey F. The efficacy of prophylaxis with low-dose warfarin for prevention of pulmonary embolism following total hip arthroplasty.  J Bone Joint Surg Am . 1997;  79 319-325
    PubMedSearch in Google Scholar
  • 65 Leclerc J R, Gent M, Hirsh J, Geerts W H, Ginsberg J S. The incidence of symptomatic venous thromboembolism during and after prophylaxis with enoxaparin: a multi-institutional cohort study of patients who underwent hip or knee arthroplasty. Canadian Collaborative Group.  Arch Intern Med . 1998;  158 873-878
    CrossrefPubMedSearch in Google Scholar
  • 66 Cohen A T, Mohamed M S, Kakkar V V. The clinical experience of reviparin in the prevention of deep vein thrombosis.  Drugs Today . 1995;  31 5-9
    PubMedSearch in Google Scholar
  • 67 Paiement G D, Wessinger S J, Hughes R, Harris W H. Routine use of adjusted low-dose warfarin to prevent venous thromboembolism after total hip replacement.  J Bone Joint Surg Am . 1993;  75 893-898
    PubMedSearch in Google Scholar
  • 68 Cohen A T, Skinner J A, Kakkar V V. Antiplatelet treatment for thromboprophylaxis: a step forward or backwards?.  BMJ . 1994;  309 1213-1215
    PubMedSearch in Google Scholar
  • 69 Davies L M, Richardson G A, Cohen A T. Economic evaluation of enoxaparin as post discharge prophylaxis for deep vein thrombosis (DVT) in elective hip surgery.  Value in Health . 2000;  3 397-406
    CrossrefPubMedSearch in Google Scholar
  • 70 Detournay B, Planes A, Vochelle N, Fagnani F. Cost effectiveness of a low-molecular-weight heparin in prolonged prophylaxis against deep vein thrombosis after total hip replacement.  Pharmacoeconomics . 1998;  13 81-89
    PubMedSearch in Google Scholar
  • 71 Sarasin F P, Bounameaux H. Cost-effectiveness of prophylactic anticoagulation prolonged after hospital discharge following general surgery.  Arch Surg . 1996;  131 694-697
    PubMedSearch in Google Scholar
  • 72 Friedman R J, Dunsworth G A. Cost analyses of extended prophylaxis with enoxaparin after hip arthroplasty.  Clin Orthop . 2000;  370 171-182
    PubMedSearch in Google Scholar