Antithrombotic therapy to prevent recurrent pregnancy loss in antiphospholipid syndrome-What is the evidence?

J Thromb Haemost. 2021 May;19(5):1174-1185. doi: 10.1111/jth.15290. Epub 2021 Mar 26.


Aspirin and heparin are widely used to reduce the risk of recurrent pregnancy loss in women with antiphospholipid syndrome. This practice is based on only a few intervention studies, and uncertainty regarding benefits and risk remains. In this case-based review, we summarize the available evidence and address the questions that are most important for clinical practice. We performed a systematic review of randomized controlled trials assessing the effect of heparin (low molecular weight heparin [LMWH] or unfractionated heparin [UFH]), aspirin, or both on live birth rates in women with persistent antiphospholipid antibodies and recurrent pregnancy loss. Eleven trials including 1672 women met the inclusion criteria. Aspirin only did not increase live birth rate compared to placebo in one trial of 40 women (risk ratio [RR] 0.94; 95% confidence interval [CI] 0.71-1.25). One trial of 141 women reported a higher live birth rate with LMWH only than with aspirin only (RR 1.20; 95% CI 1.00-1.43). Five trials totaling 1295 women compared heparin plus aspirin with aspirin only. The pooled RR for live birth was 1.27 (95% CI 1.09-1.49) in favor of heparin plus aspirin. There was significant heterogeneity between the subgroups of LMWH and UFH (RR for LWMH plus aspirin versus aspirin 1.20, 95% CI: 1.04-1.38; RR for UFH plus aspirin versus aspirin 1.74, 95% CI: 1.28-2.35; I2 78.9%, p = .03). Characteristics of participants and adverse events were not uniformly reported. Heparin (LMWH or UFH) plus aspirin may improve live birth rates in women with recurrent pregnancy loss and antiphospholipid antibodies, but evidence is of low certainty.

Keywords: antiphospholipid syndrome; heparin; live birth; recurrent pregnancy loss-aspirin.

Publication types

  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Abortion, Habitual* / prevention & control
  • Anticoagulants / adverse effects
  • Antiphospholipid Syndrome* / complications
  • Antiphospholipid Syndrome* / diagnosis
  • Antiphospholipid Syndrome* / drug therapy
  • Female
  • Fibrinolytic Agents / adverse effects
  • Heparin
  • Heparin, Low-Molecular-Weight / therapeutic use
  • Humans
  • Pregnancy


  • Anticoagulants
  • Fibrinolytic Agents
  • Heparin, Low-Molecular-Weight
  • Heparin