Subscribe to RSS
Download PDF
DOI: 10.1055/s-0037-1614625
Dermatan Sulphate for the Prevention of Postoperative Venous Thromboembolism in Patients with Cancer
Study monitoring and statistical data handling were performed by Medicina Domani Pharma, Milano (L. M. Fuccella, R. Lepore) and Genova (L. Menta). The study was supported in part by a grant from Mediolanum Farmaceutici, Milano.
Publication History
Received
25 January 1999
Accepted after revision
15 April 1999
Publication Date:
11 December 2017 (online)
Summary
Background: Patients undergoing surgery for cancer are at high risk for venous thromboembolism (VTE). Agents that selectively inhibit thrombin, such as dermatan sulphate, have potential for a favourable benefit-risk ratio in the prevention of this complication.
Methods: Patients scheduled for elective abdominal, thoracic, gynecologic or urologic surgery for cancer resection, were randomised to dermatan sulphate (600 mg intramuscularly on the second day before surgery, then 300 mg once daily), or calcium heparin (5,000 IU subcutaneously t.i.d., starting 2 hours before operation). Both treatments were continued until postoperative day 7 or until adequate mobilisation was achieved. Bilateral venography was scheduled at the end of treatment. Venograms were centrally assessed in blind conditions. The study outcomes were VTE (venographically proven deep vein thrombosis [DVT] or symptomatic, objectively confirmed pulmonary embolism) and bleeding complications.
Results: At 27 centres, 842 patients were randomised and underwent surgery (418 dermatan sulphate, 424 heparin). Efficacy was assessed in 521 patients with adequate venography and/or confirmed pulmonary embolism. DVT was observed in a total of 96 patients; symptomatic non-fatal pulmonary embolism developed in 2 patients (one per group), who also had DVT at venography. Postoperative VTE occurred in 40 of 267 patients on dermatan sulphate, 15.0%, versus 56 of 254 patients on heparin, 22.0% (p = 0.033). Relative risk reduction was 32.7% (95% confidence interval, 3.1 to 53.2%). The rate of bleeding complications in all operated patients was 6.9% with dermatan sulphate and 7.5% with heparin (confidence interval for the absolute risk difference, -4.1 to 2.9%). The inhospital mortality rate was 1.2% and 1.4%, respectively.
Conclusions: In oncologic surgery, dermatan sulphate prevents VTE more effectively than heparin without increasing bleeding complications.
-
References
- 1 Gallus AS. Prevention of post-operative deep leg vein thrombosis in patients with cancer. Thromb Haemost 1997; 78: 126-32.
- 2 Levine M. Cancer patients In:. Prevention of venous thromboembolism Goldhaber SZ. ed. New York: Marcel Dekker; 1993: 463-83.
- 3 Huber O, Bounameaux H, Borst F, Rohner A. Postoperative pulmonary embolism after hospital discharge: an underestimated risk. Arch Surg 1992; 127: 310-3.
- 4 Clagett GP, Anderson FA, Geerts W, Heit J, Knudson M, Lieberman JR, Merli GJ, Wheeler HB. Prevention of venous thromboembolism. Chest 1998; 114: 531S-60S.
- 5 Weinmann EE, Salzman EW. Deep-vein thrombosis. N Engl J Med 1994; 331: 1630-41.
- 6 Clagett GP, Reisch JS. Prevention of venous thromboembolism in general surgical patients. Ann Surg 1988; 208: 227-40.
- 7 ENOXACAN Study Group. The efficacy and safety of enoxaparin vs un-fractionated 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: 1099-103.
- 8 McLeod RS, Geerts WH, Sniderman K, Greenwood C. et al. Thromboprophylaxis after colorectal surgery – results of a randomized, double-blind comparison of low dose heparin and enoxaparin. Thromb Haemost 1997; supplement 753 abstract PD-3078.
- 9 The European Fraxiparine 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: 1058-63.
- 10 Bergqvist D, Burmark U, Frisell J, Guilbaud O. et al. Thromboprophylactic effect of low molecular weight heparin started in the evening before general abdominal surgery: a comparison with low-dose heparin. Semin Thromb Hemost 1990; 16 (Suppl) 19-24.
- 11 Nurmohamed MT, Verhaeghe R, Haas S, Iriarte JA, Vogel G, Van Rij AM, Prentice CR, Ten Cate JW. 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: 567-71.
- 12 Nurmohamed MT, Rosendaal FR, Buller HR, Dekker E, Hommes DW, Vandenbroucke JP, Briet E. Low-molecular-weight heparin versus standard heparin in general and orthopaedic surgery: a meta-analysis. Lancet 1992; 340: 152-6.
- 13 Koch A, Bouges S, Ziegler S, Dinkel H, Daures JP, 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: 750-9.
- 14 Tollefsen DM, Petska CA, Monafo WJ. Activation of heparin cofactor II by dermatan sulfate. J Biol Chem 1983; 258: 6713-6.
- 15 Bendayan P, Boneu B, Boccalon H. Dermatan sulfate is a more potent inhibitor of clot-bound thrombin than un-fractionated and low molecular weight heparins. Thromb Haemost 1994; 71: 576-80.
- 16 Agnelli G, Gianese F. Dermatan sulfate: biological and pharmacological properties; clinical applications. In:. Prevention of venous thromboembolism Goldhaber SZ. ed Marcel Dekker; New York: 1993: 287-313.
- 17 Carrié D, Caranobe C, Gabaig AM, Larroche M, Boneu B. Effects of heparin, dermatan sulfate and of their association on the inhibition of venous thrombosis growth in the rabbit. Thromb Haemost 1992; 68: 637-41.
- 18 Matthiasson SE, Lindblad B, Stjernquist U, Bergqvist D. The haemorrhagic effect of low molecular weight heparins, dermatan sulphate and hirudin. Haemostasis 1995; 25: 203-11.
- 19 Cohen AT, Phillips MJ, Edmondson RA, Skinner JA, Das SK, Cooper DJ, Thomas EM, Melissari E, Kakkar VV. A dose ranging study to evaluate dermatan sulphate in preventing deep vein thrombosis following total hip arthroplasty. Thromb Haemost 1994; 72: 793-8.
- 20 Agnelli G, Cosmi B, Di Filippo P, Ranucci V. et al. A randomised, double-blind, placebo-controlled trial of dermatan sulphate for prevention of deep vein thrombosis in hip fracture. Thromb Haemost 1992; 67: 203-8.
- 21 Prandoni P, Meduri F, Cuppini S, Toniato A, Zangrandi F, Polistena P, Gianese F, Maffei Faccioli A. Dermatan sulfate: a safe approach to prevention of postoperative deep vein thrombosis. Br J Surg 1992; 79: 505-9.
- 22 Imbimbo BP, Sié P, Agnelli G, Saivin S, Dupouy D, Damiani M, Houin G, Gianese F. Intramuscular dermatan sulfate MF701 in patients with hip fracture: relationship between pharmacokinetics and antithrombotic efficacy. Thromb Haemost 1994; 71: 553-7.
- 23 Rabinov K, Paulin S. Roentgen diagnosis of venous thrombosis in the leg. Arch Surg 1972; 104: 134-44.
- 24 PIOPED Investigators. Value of the ventilation/perfusion scan in acute pulmonary embolism Results of the prospective investigation of pulmonary embolism diagnosis. JAMA 1990; 263: 2753-9.
- 25 Makuch R, Simon R. Sample size requirements for evaluating a conservative therapy. Cancer Treat Rep 1978; 62: 1037-40.
- 26 Collins R, Scrimgeour A, Yusuf S, Peto R. Reduction in fatal pulmonary embolism and venous thrombosis by perioperative administration of subcutaneous heparin. N Engl J Med 1988; 318: 1162-73.
- 27 Lohr JM, James KV, Deshmukh RM, Hasselfeld KA. Calf vein thrombi are not a benign finding. Am J Surg 1995; 170: 86-90.
- 28 Gallus A, Cade J, Ockelford P, Hepburn S, Maas M, Magnani H, Bucknall T, Stevens J, Porteous F. Orgaran (Org 10172) or heparin for preventing venous thrombosis after elective surgery for malignant disease? A double. blind, randomised, multicentre comparison. Thromb Haemost 1993; 70: 562-7.