Comparison of enoxaparin and standard heparin in gynaecologic oncologic surgery: A randomised prospective double-blind clinical study

Objective: This study aimed to compare the haemorrhagic complications and efficacy of enoxaparin, a low molecular weight heparin (LMWH), and conventional standard heparin (SH) in gynaecological oncologic surgery.

Materials methods: A double blind, randomised trial was performed on 102 consecutive women undergoing gynaecologic cancer surgery with pelvic and paraaortic lymphadenectomy. The women were separated into those who were given 2,500 IU enoxaparin once daily and SH in a dose of 5,000 IU three times daily. The groups were analysed for intraoperative blood loss, drainage, transfusion requirements, perioperative haemoglobin decrease, wound haematoma, and clinical deep venous thrombosis.

Results: The two groups were well matched for age, weight, and other factors, which could predispose to the development of deep venous thrombosis (DVT) and haemorrhage. No patient developed clinical significant DVT, wound haematoma or intra-abdominal bleeding. There was no significant difference in bleeding complications between the two regimens. The antiFXa level in the plasma was correlated strongly with patient weight.

Conclusions: A dose of 2,500 IU enoxaparin/day does not cause more bleeding complications than SH 5,000 IU three times daily when used to prevent thrombosis. However, the dose of enoxaparin must be adjusted to the patient's weight.

Enoxaparin; Gynaecologic oncology; Haemorrhage; AntiFXa

[1] Freedman K. B., Brookenthal K. R., Fitzgerald R.H. Jr., Williams S., Lonner J. H.: "A meta-analysis of thromboembolic prophylaxis following elective total hip arthroplasty". J. Bone Joint Surg. Am., 2000, 82-A, 929.

[2] Lensing A. W., Prins M. H., Davidson B. L., Hirsh J.: "Treatment of deep venous thrombosis with low-molecular-weight heparins. A meta-analysis (see comments)". Arch. Intern. Med., 1995, 155, 601.

[3] Palmer A. J., Koppenhagen K., Kirchhof B., Weber U., Bergemann R.: "Efficacy and safety of low molecular weight heparin, unfractionated heparin and warfarin for thrombo-embolism prophylaxis in orthopaedic surgery: a meta-analysis of randomised clinical trials". Haemostasis, 1997, 27, 75.

[4] Palmer A. J., Schramm W., Kirchhof B., Bergemann R.: "Low molecular weight heparin and unfractionated heparin for prevention of thrombo-embolism in general surgery: a meta-analysis of randomised clinical trials". Haemostasis, 1997, 27, 65.

[5] Kakkar V. V., Cohen A. T., Edmonson R. A., Phillips M. J., Cooper D. J., Das S. K. et al.: "Low molecular weight versus standard heparin for prevention of venous thromboembolism after major abdominal surgery. The Thromboprophylaxis Collaborative Group (see comments)". Lancet, 1993, 341, 259.

[6] Kakkar V. V., Boeckl 0., Boneu B., Bordenave L., Brehm 0. A., Brucke P. 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, 2, discussion 8.

[7] Nurmohamed M. T., Rosendaal F. R., Buller H. R., Dekker E., Hommes D. W., Vandenbroucke J. P., Briet E.: "Low-molecularweight heparin versus standard heparin in general and orthopaedic surgery: a meta-analysis". Lancet, 1992, 340, 152.

[8] SamamaM., Combe S.: "Prevention of thromboembolic disease in general surgery with enoxaparin (Clexane)". Acta Chir. Scand. Suppl., 1990, 556, 91.

[9] Gazzaniga G. M., Angelini G., Pastorino G., Santoro E., Lucchini M., Dal Pra M. L.: "Enoxaparin in the prevention of deep venous thrombosis after major surgery: multicentric study. The Italian Study Group". Int. Surg., 1993, 78, 271.

[10] Haas S., Flosbach C. W.: "Prevention of postoperative thromboembolism with enoxaparin in general surgery: a German multicenter trial". Semin. Thromb. Hemost., 1993, 19, 164.

[11] Borstad E., Urdal K., Handeland G., Abildgaard U.: "Comparison of low molecular weight heparin vs. unfractionated heparin in gyneco logical surgery". Acta Obst et. Gynecol. Scand., 1988, 67, 99.

[12] Borstad E., Urda! K., Handeland G., Abildgaard U.: "Comparison of low molecular weight heparin vs. unfractionated heparin in gynecological surgery, II: Reduced dose of low molecular weight heparin". Acta Ob stet. Gynecol. Sc and., 1992, 71, 471.

[13] Prevention of venous thromboembolism. International Consensus Statement (guidelines according to scientific evidence). Int. Angiol.,1997,16, 3.

[14] Dickinson L. D., Miller L. D., Patel C. P., Gupta S. K.: "Enoxaparin increases the incidence of postoperative intracranial hemorrhage when initiated preoperatively for deep venous thrombosis prophylaxis in patients with brain tumors". Neurosurgery, 1998, 43, 1074.

[15] Stern S. H., Wixson R. L., O'Connor D.: "Evaluation of the safety and efficacy of enoxaparin and warfarin for prevention of deep vein thrombosis after total knee arthroplasty". J. Arthroplasty, 2000, 15, 153.

[16] Shaieb M. D., Watson B. N., Atkinson R. E.: "Bleeding complications with enoxaparin for deep venous thrombosis prophylaxis". J. Arthroplasty, 1999, 14, 432.

[17] Vitoux J. F., Aiach M., Roncato M., Fiessinger J. N.: "Should thromboprophylactic dosage of low molecular weight heparin be adapted to patient's weight? (letter)". Thromb. Haemost., 1988, 59,120.

[18] Kirchmaier C. M., Lindhoff-Last E., Rubesam D., Scharrer I., Vigh Z., Mosch G. et al.: "Regression of deep vein thrombosis by i.v.-administration of a low molecular weight heparin-results of a pilot study". Thromb. Res., 1994, 73, 337.

[19] Harenberg J., Huck K., Bratsch H., Stehle G., Dempfle C. E., Mall K. et al.: "Therapeutic application of subcutaneous low-molecular-weight heparin in acute venous thrombosis". Haemostasis, 1990, 20, 205.

[20] Harenberg J., Schmidt J. A., Koppenhagen K., Tolle A., Huisman M. V., Buller H. R.: "Fixed-dose, body weight-independent subcutaneous LMW heparin versus adjusted dose unfractionated intravenous heparin in the initial treatment of proximal venous thrombosis. EASTERN Investigators". Thromb. Haemost., 2000, 83,652.

[21] Leclerc J. R., Geerts W. H., Desjardins L., Laflamme G. H., L'Esperance B., Demers C. et al.: "Prevention of venous thromboembolism after knee arthroplasty. A randomized, double-blind trial comparing enoxaparin with warfarin (see comments)". Ann. Intern. Med., 1996, 124, 619.

[22] 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.

[23] Westrich G. H, Haas S. B., Mosca P., Peterson M.: "Meta-analysis of thromboembolic prophylaxis after total knee arthroplasty". J. Bone Joint Surg. Br., 2000, 82, 795.

[24] Levine M. N., Planes A., Hirsh J., Goodyear M., Vochelle N., Gent M.: "The relationship between anti-factor Xa level and clinical outcome in patients receiving enoxaparine low molecular weight heparin to prevent deep vein thrombosis after hip replacement". Thromb. Haemost., 1989, 62, 940.

[25] Bara L., Planes A., Samama M. M.: "Occurrence of thrombosis and haemorrhage, relationship with anti-Xa, anti-Ila activities, and D-dimer plasma levels in patients receiving a low molecular weight heparin, enoxaparin or tinzaparin, to prevent deep vein thrombosis after hip surgery". Br. J. Haematol., 1999, 104, 230.