Pregnancy and heparin: prolonged use led to a small reduction in femur bone density.

Clinical bottom line (level 4)

  1. Women who took heparin during pregnancy had a significant decrease in bone density postpartum.
Barbour et al: American Journal of Obstetrics and Gynaecology 1994; 170: 862-869
Expires June 2003

The study

Case-control study with unblinded, unobjective outcomes, not adjusted for confounding factors, not validated in an independent set of patients.

Setting: university hospital, USA

28 patients (aged mean 28 years, 100% female) pregnant women

Excluded if
  • underlying bone diseases
  • renal disease
  • thyroid dysfunction
  • on long-term steroids
  • morbidly obese


    • Cases: 14 patients (100% female, mean age -): with venous thromboembolism and receiving 12,000-21,000 units of heparin /day if low risk (previous VTE without clear cause) so that anti-factor Xa 0.05-0.2 IU/ml; receiving 23,000-50,000 units of heparin/day if high risk (acute DVT, heart valves, history of VTE with thrombophilia) so that aPTT 1.5-2.5
    Controls: 14 patients (100% female, mean age -): no venous thromboembolism or heparin


    Outcomes studied:
    • Patients were followed for 6 months.

    The evidence

    • Dual photon densimetry was used to measure bone density of femur and lumbar vertebrae.
    • femur bone density (gm/cm ³ ) (SD) at baseline:
      • control- 0.980 (0.092)
      • case- 0.943 (0.154)
      • mean difference (95% CI)- 0.037 (-0.062 to 0.14)
    • femur bone density immediately postpartum:
      • control- 0.972 (0.088)
      • case- 0.891 (0.107)
      • mean difference- 0.081 (0.005 to 0.16)
    • femur bone density 6 months postpartum:
      • control- 0.954 (0.099)
      • case- 0.906 (0.145)
      • mean difference- 0.048 (-0.048 to 0.14)
    • There was no significant difference noted in lumbar vertebrae.
    • No venous thromboembolism occurred.

    Comments

    1. The study was too small to demonstrate a dose-response relationship.
    2. Given the side-effects of treatment, for the use of heparin the indication must be convincing, the possibility of underlying bone disease must be evaluated, calcium supplementation should be given and the use of LMW rather than unfractionated heparin should be considered.

    Citation

    1. Barbour LA, Kick SD, Steiner JF, et al: A prospective study of heparin-induced osteoporosis in pregnancy using bone densimetry. American Journal of Obstetrics and Gynaecology 1994; 170: 862-869
    Contributor: Chris Ball and Clare Wotton, June 2000
    Reviewer: George Carson

    Clinical Question.
    Patient pregnant women with VTE
    Intervention or Exposure heparin
    Outcome bone density