Thromb Haemost 1989; 62(03): 940-944
DOI: 10.1055/s-0038-1651032
Original Article
Schattauer GmbH Stuttgart

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

M N Levine
*   The Departments of Medicine, Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ont., Canada
,
A Planes
+   The Clinique Radio-Chirurgicale du Mail, La Rochelle, France
,
J Hirsh
*   The Departments of Medicine, Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ont., Canada
,
M Goodyear
*   The Departments of Medicine, Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ont., Canada
,
N Vochelle
+   The Clinique Radio-Chirurgicale du Mail, La Rochelle, France
,
M Gent
*   The Departments of Medicine, Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ont., Canada
› Author Affiliations
Further Information

Publication History

Received: 21 November 1988

Accepted after revision 30 May 1989

Publication Date:
30 June 2018 (online)

Summary

Studies in experimental animals have demonstrated that there is a relationship between levels of low molecular weight (LMW) heparin and both bleeding and inhibition of thrombosis. The relationship between these outcomes and ex vivo anti-factor Xa levels has been examined in 163 patients undergoing total hip replacement who were given prophylaxis once daily with a LMW heparin (enoxaparine). Fifty patients received 60 mg of enoxaparine and 113 received 40 mg, both regimens being administered subcutaneously once daily. Blood samples for anti-factor Xa levels were collected 12 hours after the injection on the day of surgery and on days 1, 3 and 6, postoperatively. The incidence of wound hematoma was 5.3% when the maximum anti-factor Xa level was ≤0.2 units per ml, but increased to 24.5% when the anti-factor Xa level exceeded 0.2 units per ml, P = 0.0008. The incidence of postoperative thrombosis was low (6.3%) if the minimum anti-factor Xa level exceeded 0.1 units per ml, but increased to 14.6% when ≤0.1 units per ml, and to 18.8% if the anti-factor Xa level was ≤0.05 units per ml. Regression analysis revealed that there was a statistically significant relationship between anti-factor Xa level and wound hematoma, P = 0.002 and anti-factor Xa level and thrombosis, P = 0.03. These findings suggest that when enoxaparine is administered as a once daily subcutaneous injection, the 12 hour anti-factor Xa level should not exceed 0.2 units per ml to minimize bleeding and levels >0.05 units per ml should be obtained to optimize efficacy.

 
  • References

  • 1 Carter CJ, Kelton JG, Hirsh J, Cerskus A, Santos AV, Gent M. The relationship between the hemorrhagic and antithrombotic properties of low molecular weight heparin in rabbits. Blood 1982; 59: 1239-1245
  • 2 Ockelford PA, Carter CJ, Cerskus A, Smith CA, Hirsh J. Comparison of the in vivo hemorrhagic and antithrombotic effects of a low antithrombin III affinity heparin fraction. Thromb Res 1982; 27: 679-690
  • 3 Ockelford PA, Carter CJ, Mitchell L, Hirsh J. Discordance between the anti-Xa activity and the antithrombotic activity of an ultra-low molecular weight heparin fraction. Thromb Res 1982; 28: 401-409
  • 4 Fernandez FA, N'guyen P, Van Ryn J, Ofosu FA, Hirsh J, Buchanan MR. Hemorrhagic doses of heparin and other glycosaminoglycans induce a platelet effect. Thromb Res 1986; 43: 491-495
  • 5 Hirsh J, Ofosu FA, Levine M. The development of low molecular weight heparins for clinical use. In: Thrombosis and Haemostasis 1987. Verstraete M, Vermylen J, Lijnen R, Amout J. (eds). Leuven University Press; Leuven: 1987. pp 325-348
  • 6 Levine MN, Hirsh J. Clinical use of low molecular weight heparins and heparinoids. Semin Thromb Haemostas 1988; 14: 116-125
  • 7 ten Cate H, Henny CH P, ten Cate JW, Btiller HR, Dabhoiwala NF. Randomized double-blind, placebo controlled safety study of low molecular weight heparinoid in patients undergoing transurethral resection of the prostate. Thromb Haemostas 1987; 57: 92-96
  • 8 Planes A, Vochelle N, Ferru J, Przyrowski D, Clerc J, Fagola M, Planes M. Enoxaparine low molecular weight heparin: its use in the prevention of deep venous thrombosis following total hip replacement. Haemostasis 1986; 16: 152-158
  • 9 Planes A, Vochelle N, Mansat C. Prevention of deep vein thrombosis after total hip replacement by enoxaparine: one daily injection of 40 mg versus two daily injections of 20 mg. Thromb Haemostas 1987; 117 (Abstr 415).
  • 10 Planes A, Vochelle N, Mazas F, Mansat C, Zucman J, Landais A, Pascariello JC, Weill D, Butel J. Prevention of postoperative venous thrombosis: a randomized trial comparing unfractionated heparin with low molecular weight heparin in patients undergoing total hip replacement. Thromb Haemostas 1988; 60: 407-410
  • 11 Aiach M, Michaud A, Balian JL, Lefebvre M, Woler M, Fourtillan J. A new low molecular weight heparin derivative: in vitro and in vivo studies. Thromb Res 1983; 31: 611-621
  • 12 Colton T. Statistics in Medicine. Little; Brown, Boston: 1974. pp 127-146
  • 13 Fleiss JL. Statistical Methods for Rates and Proportions. 2nd ed. John Wiley; New York: 1981. pp 19-27
  • 14 Armitage P. Tests for linear trends in proportions and frequencies. Biometrics 1955; 11: 375-386
  • 15 Cox DR. The analysis of binary data. Methuen; London: 1970. pp 14-26
  • 16 Turpie AG G, Levine MN, Hirsh J, Carter CJ, Jay RM, Powers PJ, Andrew M, Hull RD, Gent M. A randomized controlled trial of a low molecular weight heparin (enoxaparine) to prevent deep vein thrombosis in patients undergoing elective hip surgery. N Engl J Med 1987; 315: 925-929
  • 17 Samama M, Bernard P, Bonnardot VP, Tissot E, Lanson Y, Combe-Tamzali S. Low molecular weight heparin (enoxaparine) compared with unfractionated heparin thrice in day in prevention of postoperative thrombosis. Br J Surg 1988; 75: 128-131
  • 18 Bergqvist 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 multi-centre trial on prevention of postoperative thrombosis. Br J Surg 1986; 73: 204-208
  • 19 Roller M, Schoch U, Buchmann P, Largiader F, Von Felten A, Frick PG. Low molecular weight heparin (KABI-2165) as thromboprophylaxis in elective visceral surgery. A randomized double-blind study versus unfractionated heparin. Thromb Haemostas 1986; 56: 243-246
  • 20 Caen JP. A randomized double-blind study between a low molecular weight heparin KABI 2165 and standard heparin in the prevention of deep vein thrombosis in general surgery. Thromb Haemostas 1988; 59: 216-220
  • 21 Vitoux JF, Aiach M, Roncato M, Fiessinger JN. Should thrombo-prophylactic dosage of low molecular weight heparin be adapted to patient's weight?. Thromb Haemostas 1988; 59: 120