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)

Paul A Ockelford; Janet Patterson; Allan S Johns

doi:10.1055/s-0038-1647114

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1989; 62(04): 1046-1049
DOI: 10.1055/s-0038-1647114

Original Article

Clinical Studies

Schattauer GmbH Stuttgart

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)

Paul A Ockelford

The Section of Haematology, Department of lmmunobiology, School of Medicine, University of Auckland, New Zealand

,

Janet Patterson

The Section of Haematology, Department of lmmunobiology, School of Medicine, University of Auckland, New Zealand

,

Allan S Johns

The Section of Haematology, Department of lmmunobiology, School of Medicine, University of Auckland, New Zealand

› Author Affiliations

Abstract

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Summary

The safety and efficacy of the low molecular weight heparin fragment (Fragmin) administered as a single daily injection of 2,500 anti Xa units has been evaluated in 183 patients undergoing major elective general surgery. The study was double-blinded and placebo controlled. The active agent, or placebo, was given subcutaneously with the preoperative medication and continued postoperatively for 5-9 days. Ninety five patients received Fragmin and 88 were randomized to receive the placebo. The clinical characteristics of the two treatment groups were similar. Fragmin significantly reduced the incidence of deep venous thrombosis, as detected by a positive ¹²⁵I fibrinogen leg scan, relative to the placebo treated patients (4/95, 4.2%; v. 14/88, 15.9%; p = 0.008). The thrombotic events occurred predominantly (73%) amongst patients with malignancy. Haemorrhagic endpoints necessitating discontinuation of the trial treatment were 4% in each group. No severe adverse reactions or drug related deaths occurred. These results indicate that 2,500 anti Xa units of Fragmin given only once daily is effective thromboprophylaxis for patients undergoing major elective abdominal surgery.

Keywords

Heparin - Low molecular weight heparin - Venous thrombosis prophylaxis - General surgery - Randomized trial

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References

References
1 Colditz GA, Tuden RL, Oster G. Rates of venous thrombosis aftergeneral surgery: combined results of randomised clinical trials. Lancet 1986; 2: 143-146
2 Conti S, Daschbach B. Venous thromboembolism prophylaxis; a survey of its use in the United States. Arch Surg 1982; 117: 1036-1040
3 Dawes J, Prowse CV, Pepper DS. Absorption of heparin, LMW heparin and SP54 after subcutaneous injection, assessed by competitive binding assay. Thromb Res 1986; 44: 683-693
4 Bergquist D, Hedner U, Sjorin E, Holmer E. Anticoagulant effects of two types of low molecular weight heparin administered subcutaneously. Thromb Res 1983; 32: 381-391
5 Carter CJ, Kelton JG, Hirsh J, Cerskus A, Santos AV, Gent M. The relationship between the haemorrhagic and antithrombotic properties of low molecular weight heparin in rabbits. Blood 1982; 59: 1239-1245
6 Kakkar KK, Djazaeri B, Fok J, Fletcher M, Scully MF, Westwick J. Low molecular weight heparin and prevention of postoperative deep vein thrombosis. Br Med J 1982; 284: 375-379
7 Kakkar VV, Murray W JG. Efficacy and safety of low molecular weight heparin (CY 216) in preventing postoperative venous thromboembolism: a cooperative study. Br J Surg 1985; 72: 786-791
8 Koller M, Schoch U, Buchmann P, Largiader F, Von Felten A, Frick PG. Low molecular weight heparin (Kabi 2165) as thromboprophylaxis in elective visceral surgery. Thromb Haemostas 1986; 56: 243-246
9 Bergquist D, Burmark US, Frisell J. et al Low molecular weight heparin once daily compared with conventional low-dose heparin twice daily. A prospective double-blind multicentre trial on prevention of postoperative thrombosis Br J Surg 1986; 73: 204-208
10 Turpie AG G, Levine MN, Hirsh J. et al A randomised controlled trial of a low molecular weight heparin (Enoxaparin) to prevent deep vein thrombosis in patients undergoing elective hip surgery. N Engl J Med 1986; 315: 925-929
11 Teien AN, Lie M, Abildgaard U. Assay of heparin in plasma using a chromogenic substrate for activated factor X. Thromb Res 1976; 8: 413-416
12 Kakkar VV, Nicolaides AN, Renney JT G, Friend JR, Clarke MD. ¹²⁵I-fibrinogen uptake test adopted for routine screening. Lancet 1970; 1: 540-542
13 Negus D, Pinto DJ, Le Quesne LP, Brown N, Chapman M. ¹²⁵I-labelled fibrinogen in the diagnosis of deep-vein thrombosis and its correlation with phlebography. Br J Surg 1968; 55: 835-839
14 Flanc C, Kakkar VV, Clarke MB. The detection of venous thrombosis of the legs using ₁₂₅I-labelled fibrinogen. Br J Surg 1968; 55: 742-747
15 Colton T. Statistics in Medicine. 1. ed Little, Brown and Co.; Boston: 1974
16 Kakkar VV. Prevention of venous thromboembolism. In: Haemostasis and Thrombosis. Bloom AL, Thomas DP. (Eds) Churchill Livingstone; New York: 1981. pp 669-683
17 Salzman EW, Hirsh J. Prevention of venous thromboembolism. In: Haemostasis and Thrombosis: Basic Principles and Clinical Practice. Colman RW, Hirsh J, Marder VJ, Salzman EW. (Eds) J B Lippincott; Philadelphia: 1982. pp 986-999
18 International Multicentre Trial. Prevention of postoperative pulmonary embolism by low doses of heparin. Lancet 1975; 2: 45-51
19 Gallus AS, Hirsh J, Tuttle RJ, Trebilcock R, O’Brien SE. Small subcutaneous doses of heparin in the prevention of venous thrombosis. N Engl J Med 1973; 288: 545
20 Collins R, Scrimgeous A, Yusuf SJ, Peto R. Reduction in fatal pulmonary embolism and venous thrombosis by perioperative administration of subcutaneous heparin. Overview of results of randomised trials in general, orthopaedic and urologic surgery N Engl J Med 1988; 318: 1162-1173