Heparin treatment in antiphospholipid syndrome with recurrent pregnancy loss: a systematic review and meta-analysis

Obstet Gynecol. 2010 Jun;115(6):1256-1262. doi: 10.1097/AOG.0b013e3181deba40.


Objective: To estimate the effect of combined heparin and aspirin compared with aspirin monotherapy in pregnant women with antiphospholipid syndrome and recurrent pregnancy loss.

Data sources: We searched the PubMed database up to December 2009 for English-language studies using the key words "aspirin AND (heparin OR low molecular weight heparin), (antiphospholipid OR anticardiolipin OR aPL) AND pregnancy."

Methods of study selection: Two hundred ninety- two studies were initially screened. Randomized controlled trials comparing the effect of heparin (unfractionated heparin or low molecular weight heparin) plus aspirin compared with aspirin alone on the live-birth rate in women with a history of at least two miscarriages and antiphospholipid antibodies were eligible.

Tabulation, integration, and results: The pooled effect of unfractionated heparin and low molecular weight heparin was evaluable in three and two randomized controlled studies, respectively, with regard to live births, which was the major outcome. Overall, treatment effects were in favor of heparin against first-trimester losses (odd ratio [OR] 0.39, 95% confidence interval [CI] 0.24-0.65, number needed to treat 6). More specifically, unfractionated heparin displayed a significant effect (OR 0.26, 95% CI 0.14-0.48, number needed to treat 4), while the pooled effect of low molecular weight heparin was insignificant (OR 0.70, 95% CI 0.34-1.45). Combination therapy of either unfractionated heparin or low molecular weight heparin with aspirin failed to display any significant effect in the prevention of late-pregnancy losses. No significant differences were observed between treatment and control groups for any other outcomes.

Conclusion: The combination of unfractionated heparin and aspirin confers a significant benefit in live births. However, the efficacy of low molecular weight heparin plus aspirin remains unproven, highlighting the urgent need for large controlled trials.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Abortion, Habitual / etiology
  • Abortion, Habitual / prevention & control*
  • Antiphospholipid Syndrome / complications
  • Antiphospholipid Syndrome / drug therapy*
  • Aspirin / therapeutic use
  • Drug Therapy, Combination
  • Female
  • Fibrinolytic Agents / therapeutic use*
  • Heparin / therapeutic use*
  • Humans
  • Pregnancy


  • Fibrinolytic Agents
  • Heparin
  • Aspirin