Women with antiphospholipid syndrome (APS) frequently experience obstetric complications, including recurrent pregnancy loss. Typically, women with the persistent presence of antiphospholipid antibodies and a history of thrombosis, as well as recurrent miscarriage, are given thromboprophylaxis during pregnancy in addition to aspirin. Treatment can take the form of antepartum administration of prophylactic- or intermediate-dose unfractionated heparin or prophylactic-dosed, low-molecular-weight heparin combined with aspirin. However, this current clinical practice is based on limited published evidence.
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A recent Cochrane Review evaluated the role of aspirin and/or heparin in improving pregnancy outcomes in APS patients. The review included women who had experienced more than one unexplained fetal death after 10 or more weeks of gestation, one or more premature delivery before 34 weeks of gestation due to severe pre-eclampsia. Placental insufficiency and three unexplained consecutive miscarriages before 10 weeks of gestation were also characterized as recurrent pregnancy loss due to APS.
The review found that for women with persistent antiphospholipid antibodies, the combination of heparin and aspirin during pregnancy—as opposed to aspirin treatment alone—may increase live birth rate. Eva N. Hamulyak, MD, PhD candidate, and colleagues at the University of Amsterdam, The Netherlands, performed a meta-analysis and found that one large study comparing low-molecular-weight heparin plus aspirin to aspirin alone drove the observed benefit of heparin. The review, published in the May issue of Cochrane Database of Systemic Reviews, also found that adverse events were not frequently, or not uniformly, reported in the included studies.1
The authors identified 11 trials that met their predefined inclusion criteria. Although only two of the trials were blinded for treatment, they assessed all the trials as being low risk for performance bias because live birth is an unequivocal outcome unlikely to be affected by treatment allocation. However, only three of the trials adhered to the timeframe of at least 12 weeks between antiphospholipid antibody tests, and the antibody cut-off levels differed greatly between trials.
None of the trials included in the systemic review had a treatment comparator arm. Thus, the review was unable to determine if aspirin alone affected live birth rate relative to placebo. Instead, the results indicate the combination of heparin, started after a positive pregnancy test, plus aspirin may slightly improve live birth rates compared with aspirin alone. The authors were unable to conclude that aspirin alone or heparin plus aspirin had any effect on the risk of pre-eclampsia, preterm delivery of a live infant, intrauterine growth restriction or adverse events in the mother or child.
When the authors evaluated low-molecular-weight heparin with aspirin vs. unfractionated heparin with aspirin, the pooled risk ratio for live birth did not reveal a clear benefit of one heparin over the other. The meta-analysis also was unable to determine the ideal timing of initiation and duration of treatment.
The studies did not report frequent occurrence of easy bruising at injection site or allergies, both of which are adverse events commonly associated with heparin therapy. Additionally, hemorrhage and heparin-induced thrombocytopenia, common side effects of unfractionated heparin therapy, were not commonly reported.
Lara C. Pullen, PhD, is a medical writer based in the Chicago area.
- Hamulyák EN, Scheres LJ, Marijnen MC, et al. Aspirin or heparin or both for improving pregnancy outcomes in women with persistent antiphospholipid antibodies and recurrent pregnancy loss. Cochrane Database Syst Rev. 2020 May 2;5(5):CD012852.