Download PDF
Thromb Haemost 2002; 87(02): 182-186
DOI: 10.1055/s-0037-1612970
In Focus
Schattauer GmbH

Postpartum Bone Mineral Density in Women Treated for Thromboprophylaxis with Unfractionated Heparin or LMW Heparin

Ville Pettilä
1   Department of Anaesthesiology and Intensive Care Medicine, Helsinki University Central Hospital, Finland
,
Pekka Leinonen
2   Departments of Obstetrics and Gynaecology, Helsinki University Central Hospital, Finland
,
Antti Markkola
3   Department of Radiology, Helsinki University Central Hospital, Finland
,
Vilho Hiilesmaa
2   Departments of Obstetrics and Gynaecology, Helsinki University Central Hospital, Finland
,
Risto Kaaja
2   Departments of Obstetrics and Gynaecology, Helsinki University Central Hospital, Finland
› Author Affiliations
Further Information

Publication History

Received 10 August 2001

Accepted after revision 28 November 2001

Publication Date:
13 December 2017 (online)

Also available at
    Permissions and Reprints

Summary

Venous thromboembolism remains an important cause of maternal mortality. In a randomised open study, 44 pregnant women with confirmed previous or current thromboembolism were randomised to receive either low-molecular-weight heparin, dalteparin (N = 21) once daily subcutaneously or unfractionated sodium heparin (UF heparin, N = 23) twice daily subcutaneously for thromboprophylaxis during pregnancy and puerperium. Bone mineral density (BMD) in the lumbosacral spine was measured with dual X-ray absorptiometry (DEXA) 1, 6, 16, 52 weeks and, if possible, 3 years after delivery. BMD values were also compared with those of healthy, delivered women (N =19).

Mean BMD of the lumbar spine was significantly lower in the unfractionated heparin group compared with the dalteparin and with the control groups (repeated measures ANOVA p = 0.02). BMD in the dalteparin group did not differ from BMD of healthy delivered women. Multiple logistic regression analysis revealed that therapy was the only independent factor influencing BMD at weeks 16 and 52. Therefore we recommend use of dalteparin instead of UF heparin for long-term thromboprophylaxis during and after pregnancy.

Keywords

Bone mineral density - osteoporosis - pregnancy - heparin - dalteparin
 

  • References

  • 1 Gates S. Thromboembolic disease in pregnancy. Curr Opin Obstet Gynecol 2000; 12: 117-22.
    CrossrefPubMedGoogle Scholar
  • 2 Nelson-Piercy C, Letsky EA, de Swiet M. Low-molecular-weight heparin for obstetric thromboprophylaxis: Experience of sixty-nine pregnancies in sixty-one women of high risk. Am J Obstet Gynecol 1997; 176: 1062-8.
    CrossrefPubMedGoogle Scholar
  • 3 De Swiet M, Floyd E, Letsky E. Low risk of recurrent thromboembolism in pregnancy (letter). Br J Hosp Med 1987; 38: 264.
    PubMedGoogle Scholar
  • 4 Howell R, Fidler J, Letsky E. The risk of antenatal subcutaneous heparin prophylaxis: a controlled trial. Br J Obstet Gynaecol 1983; 90: 1124-8.
    CrossrefPubMedGoogle Scholar
  • 5 Tengborn L, Bergqvist D, Mätzsch T, Bergqvist A, Hedner U. Recurrent thromboembolism in pregnancy and puerperium: Is there need for thromboprophylaxis?. Am J Obstet Gynecol 1989; 160: 90-4.
    CrossrefPubMedGoogle Scholar
  • 6 Badaracco MA, Vessey MP. Recurrence of venous thromboembolic disease and the use of oral contraceptives. BMJ 1974; 01: 215-7.
    CrossrefPubMedGoogle Scholar
  • 7 Brill-Edwards P, Ginsberg JS, Gent M, Hirsh J, Burrows R, Kearon C, Geerts W, Kovacs M, Weitz JI, Robinson KS, Whittom R, Couture G. Safety of withholding heparin in pregnant women with the history of venous thromboembolism. N Engl J Med 2000; 343: 1439-44.
    CrossrefPubMedGoogle Scholar
  • 8 Melissari E, Parker CJ, Wilson NV. et al. Use of low molecular weight heparin in pregnancy. Thromb Haemost 1992; 68: 652-6.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 Forestier F, Sóle Y, Aiach M, Gélas MA, Daffos F. Absence of transplacental passage of Fragmin during the second and third trimester of pregnancy. Thromb Haemost 1992; 67: 180-1.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 10 Ginsberg JS, Greer IA, Hirsch J. Use of antithrombotic agents during pregnancy. Chest 2001; 119: 122S-131S.
    CrossrefPubMedGoogle Scholar
  • 11 Heilmann L, Schneider DM, von Tempelhoff GF. Antithrombotic therapy in high-risk pregnancy. Hematol Oncol Clin North Am 2000; 14: 1133-50.
    CrossrefPubMedGoogle Scholar
  • 12 Hunt BJ, Doughty HA, Majumdar G, Copplestone A, Kerslage S, Buchanan N, Hughes G, Khamashta M. Thromboprophylaxis with low molecular weight heparin (Fragmin) in high risk pregnancies. Thromb Haemost 1997; 77: 39-43.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 13 Rey E, Rivard GE. Prophylaxis and treatment of thromboembolic diseases during pregnancy with dalteparin. Int J Gynaecol Obstet 2000; 71: 19-24.
    CrossrefPubMedGoogle Scholar
  • 14 Dulitzki M, Pauzner R, Langevitz P, Pras M, Many A, Schiff E. Lowmolecular-weight heparin during pregnancy and delivery: Preliminary experience with 41 pregnancies. Obstet Gynecol 1996; 87: 380-3.
    CrossrefPubMedGoogle Scholar
  • 15 Ellison J, Walker ID, Greer IA. Antenatal use of enoxaparin for prevention and treatment of thromboembolism in pregnancy. Br J Obstet Gyn 2000; 107: 1116-21.
    CrossrefPubMedGoogle Scholar
  • 16 Bar J, Cohen-Sacher B, Hod M, Blickstein D, Lahav J, Merlob P. Lowmolecular weight heparin for thrombophilia in pregnant women. Int J Gynaecol Obstet 2000; 69: 209-13.
    CrossrefPubMedGoogle Scholar
  • 17 Backos M, Thomas E, Murphy M, Dore C, Regan L. Bone density changes in pregnant women treated with heparin: a prospective, longitudinal study. Human Reprod 1999; 14: 2876-80.
    CrossrefPubMedGoogle Scholar
  • 18 Barbour LA, Kick SD, Steiner JF. et al. A prospective study of heparininduced osteoporosis in pregnancy using bone densitometry. Am J Obstet Gynecol 1994; 170: 862-9.
    CrossrefPubMedGoogle Scholar
  • 19 Douketis JD, Ginsberg JS, Burrows RF, Duku EK, Webber CE, BrillEdwards P. The effects of long-term heparin therapy during pregnancy on bone mineral density: prospective matched cohort study. Thromb Haemost 1996; 75: 254-7.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 20 Pettilä V, Kaaja R, Leinonen P, Ekblad U, Kataja M, Ikkala E. Thromboprophylaxis with low molecular weight heparin (dalteparin) in pregnancy. Thromb Res 1999; 96: 275-82.
    CrossrefPubMedGoogle Scholar
  • 21 Shaughnessy SG, Hirsh J, Bhandari M, Muir J, Young E, Weitz JI. Heparininduced bone loss is not reversible after stopping heparin treatment in rats. Blood. 1998 92. (suppl 1) abstr 1473.
    PubMedGoogle Scholar
  • 22 Bhandari M, Hirsh J, Weitz JI, Young E, Venner TJ, Shaughnessy SG. The effects of standard and low molecular weight heparin on bone nodule formation in vitro. Thromb Haemost 1998; 80: 413-7.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 23 Muir JM, Hirsh J, Weitz JI, Andrew M, Young E, Shaughnessy SG. A histomorfometric comparison of effects of heparin and low-molecularweight heparin on cancellous bone in rats. Blood 1997; 89: 3236-42.
    PubMedGoogle Scholar
  • 24 Murray WJ, Lindo VS, Kakkar VV, Melissari E. Long-term administrations of heparin and heparin fractions and osteoporosis in experimental animals. Blood Coagul Fibrinolysis 1995; 06: 113-8.
    CrossrefPubMedGoogle Scholar
  • 25 Casele H, Laifer SA. Prospective evaluation of bone density in pregnant women receiving the low molecular weight heparin enoxaparin sodium. J Matern Fetal Med 2000; 09: 122-5.
    PubMedGoogle Scholar
  • 26 Naylor KE, Iqbal P, Fledelius C, Fraser RB, Eastell R. The effect of pregnancy on bone density and bone turnover. J Bone Miner Res 2000; 15: 129-37.
    CrossrefPubMedGoogle Scholar
  • 27 Kolthoff N, Eiken P, Kristensen B, Nielsen SP. Bone mineral changes during pregnancy and lactation: a longitudinal study. Clin Sci (Colch) 1998; 94: 405-12.
    CrossrefPubMedGoogle Scholar
  • 28 Dahlman TC. Osteoporotic fractures and the recurrence of thromboembolism during pregnancy and puerperium in 184 women undergoing thromboprophylaxis with heparin. Am J Obstet Gynecol 1993; 168: 1265-70.
    CrossrefPubMedGoogle Scholar
  • 29 Dahlman T. Heparin and osteoporosis. Studies on longterm thromboprophylaxis in pregnancy. Academic dissertation. Stockholm, Sweden: Karolinska Hospital; 1992
    Google Scholar