Download PDF
Thromb Haemost 2005; 94(04): 867-871
DOI: 10.1160/TH04-03-0189
Cellular Proteolysis and Oncology
Schattauer GmbH

Evaluation of perioperative fatal pulmonary embolism and death in cancer surgical patients

The MC-4 cancer substudy
Ajay K. Kakkar
1   Centre for Surgical Sciences, St. Bartholomew’s and The London Hospitals Medical School, London, UK
,
Sylvia Haas
2   Institut für Experimentelle Onkologie und Therapieforschung, Technical University of Munich, Germany
,
Helmut Wolf
3   Novartis Pharma GmbH, Nürnberg, Germany
,
Albrecht Encke
4   Zentrum für Chirurgie, University of Frankfurt/Main, Germany
› Author AffiliationsGrant support:This study was supported by a grant from Novartis Pharma GmbH, Nürnberg, Germany
Further Information

Publication History

Received22 October 2002

Accepted after revision14 July 2005

Publication Date:
07 December 2017 (online)

    Permissions and Reprints

Summary

Cancer patients undergoing surgery are at a high risk of venous thromboembolism, but few studies have described the rate of autopsy-confirmed fatal pulmonary embolism after heparin thromboprophylaxis. In a post hoc analysis of a randomized study (MC-4), which compared the efficacy and safety of certoparin (3000 anti-Xa IU, subcutaneously, once-daily) with unfractionated heparin (5000 IU, subcutaneously, three-times daily) in 23078 patients undergoing surgery lasting more than 30 min, the incidence of autopsy-confirmed fatal pulmonary embolism, death and bleeding in the cancer patients (n=6124) was compared with non-cancer patients (n=16954). Fatal pulmonary embolism was significantly more frequent in cancer patients (0.33% [20/6124]) than in non-cancer patients (0.09% [15/16954], relative risk (RR), 3.7 [95% confidence intervals (CI), 1.80, 7.77], p=0.0001) at 14 days post-prophylaxis. Perioperative mortality was also significantly higher in cancer patients than in noncancer patients (3.14% [192/6124] vs. 0.71% [120/16954], RR, 4.54 [95% CI, 3.59, 5.76], p=0.0001), as were blood loss (p<0.0001), and transfusion requirements (p<0.0001). Prevention of venous thromboembolism in cancer surgical patients remains a clinical challenge.

Keywords

Cancer surgery - thromboprophylaxis - fatal pulmonary embolism - death
 

  • References

  • 1 Trousseau A. Phlegmasia alba dolens. In: Cliniques Medicales de l’Hotel-Dieu de Paris.. Paris: JB Balliere et Fils; 1865
    Google Scholar
  • 2 Geerts WH, Pineo GF, Heit JA. et al. Prevention of venous thromboembolism: The seventh ACCP conference on antithrombotic and thrombolytic therapy. Chest 2004; 126 (Suppl) 338S-400S.
    CrossrefPubMedGoogle Scholar
  • 3 Kakkar AK, Williamson RC. Prevention of venous thromboembolism in cancer patients. Semin Thromb Hemost 1999; 25: 239-43.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 4 Lee AY. Management of thrombosis in cancer: primary prevention and secondary prophylaxis. Br J Haematol 2005; 128: 291-302.
    CrossrefPubMedGoogle Scholar
  • 5 Lee AY, Levine MN. The thrombophilic state induced by therapeutic agents in the cancer patient. Semin Thromb Hemost 1999; 25: 137-45.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 6 Deitcher SR, Gomes MP. The risk of venous thromboembolic disease associated with adjuvant hormone therapy for breast carcinoma: a systematic review. Cancer 2004; 101: 439-49.
    CrossrefPubMedGoogle Scholar
  • 7 Nicolaides AN, Breddin HK, Fareed J. et al. Prevention of venous thromboembolism. International Consensus Statement. Guidelines compiled in accordance with the scientific evidence. Int Angiol 2001; 20: 1-37.
    PubMedGoogle Scholar
  • 8 Clagett GP, Reisch JS. Prevention of venous thromboembolism in general surgical patients. Results of meta-analysis. Ann Surg 1988; 208: 227-40.
    CrossrefPubMedGoogle Scholar
  • 9 ENOXACAN Study Group.. Efficacy and safety of enoxaparin versus UFH for prevention of deep vein thrombosis in elective cancer surgery: a double-blind randomized multicentre trial with venographic assessment. Br J Surg 1997; 84: 1099-103.
    CrossrefPubMedGoogle Scholar
  • 10 Bergqvist D, Burmark US, Flordal PA. 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.
    CrossrefPubMedGoogle Scholar
  • 11 Gallus AS. Prevention of post-operative deep leg vein thrombosis in patients with cancer. Thromb Haemost 1997; 78: 126-32.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 12 Lee AY. Management of thrombosis in cancer: primary prevention and secondary prophylaxis. Br J Haematol 2005; 128: 291-302.
    CrossrefPubMedGoogle Scholar
  • 13 Prevention of fatal postoperative PE by low doses of heparin – An international multicentre trial. Lancet 1975; 2: 145-51.
    PubMedGoogle Scholar
  • 14 Haas S, Wolf H, Kakkar A. et al. Prevention of fatal pulmonary embolism and mortality in surgical patients – a double blind comparison of low-molecular-weight heparin with unfractionated heparin. Thromb Haemost 2005; 94: 814-9.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 15 Kakkar AK, DeRuvo N, Chinswangwatanakul V. et al. Extrinsic-pathway activation in cancer with high factor VIIa and tissue factor. Lancet 1995; 346: 1004-5.
    CrossrefPubMedGoogle Scholar
  • 16 Falanga A, Rickles FR. Pathophysiology of the thrombophilic state in the cancer patient. Semin Thromb Hemost 1999; 25: 173-82.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 17 Rickles FR, Edwards RL. Activation of blood coagulation in cancer: Trousseau’s syndrome revisited. Blood 1983; 62: 14-31.
    CrossrefPubMedGoogle Scholar
  • 18 Pineo GF, Brain MC, Gallus AS. et al. Tumors, mucus production, and hypercoagulability. Ann N Y Acad Sci 1974; 230: 262-70.
    CrossrefPubMedGoogle Scholar
  • 19 Bergqvist D, Agnelli G, Cohen AT. et al. Duration of prophylaxis against venous thromboembolism with enoxaparin after surgery for cancer. N Engl J Med 2002; 346: 975-980.
    CrossrefPubMedGoogle Scholar
  • 20 Rasmussen M, Jørgensen L, Wille-Jørgensen P. et al. Prolonged prophylaxis with dalteparin after major abdominal surgery. Thromb Haemost. 2001 OC 1733.
    PubMedGoogle Scholar
  • 21 Collins R, Scrimgeour A, Yusuf S. et al. Reduction in fatal PE 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: 1162-73.
    CrossrefPubMedGoogle Scholar