Bloody mess

Abstract

Women with positive antiphospholipid antibodies may present with severe preeclampsia, fetal growth restriction (FGR), fetal demise, and recurrent miscarriage.1Ziakas P.D. Pavlou M. Voulgarelis M. Heparin treatment in antiphospholipid syndrome with recurrent pregnancy loss A systematic review and meta-analysis.Obstet Gynecol. 2010; 115: 1256-1262Crossref PubMed Scopus (137) Google Scholar, 2Branch D.W. Silver R.M. Porter T.F. Obstetric antiphospholipid syndrome: current uncertainties should guide our way.Lupus. 2010; 19: 446-452Crossref PubMed Scopus (28) Google Scholar In addition, these women are at increased risk of arterial and venous thrombosis.3American College of Obstetricians and GynecologistsACOG practice bulletin no. 118.Antiphospholipid syndrome. January 2011; Google Scholar As a result, testing for these antibodies is increasing in women with such complications and those with positive tests for lupus anticoagulant, anticardiolipin, or anti-B2 glycoprotein I are considered to have the antiphospholipid antibody syndrome (APS). Once APS is diagnosed, the essential question is whether any treatment, beyond counseling and close observation in subsequent pregnancy, is necessary. During the past 2 decades, several authors suggested using heparin with or without aspirin to improve pregnancy outcome in women with APS.2Branch D.W. Silver R.M. Porter T.F. Obstetric antiphospholipid syndrome: current uncertainties should guide our way.Lupus. 2010; 19: 446-452Crossref PubMed Scopus (28) Google Scholar, 3American College of Obstetricians and GynecologistsACOG practice bulletin no. 118.Antiphospholipid syndrome. January 2011; Google Scholar There are no randomized trials evaluating the benefits of such therapy in women with prior severe preeclampsia, FGR, or fetal demise. There are 9 randomized or pseudorandomized trials evaluating heparin with aspirin, aspirin alone, or a placebo in patients with recurrent miscarriage and APS. The results of these trials are inconsistent.4Miyakis S. Lockshin M.D. Atsumi T. et al.International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome.J Thromb Haemost. 2006; 4: 295-306Crossref PubMed Scopus (4921) Google Scholar Of interest, the rate of live birth in the placebo subjects (n = 28) ranged from 85% to 100%; in the aspirin-only subjects (n = 207), the rate was 42-90%; in the unfractionated heparin-plus-aspirin subjects (n = 113), the rate was 31-85%; and in the low-molecular-weight heparin-plus-aspirin subjects (n = 111), it was 69-84%. In 2006, the laboratory criteria for APS have been revised,5Laskin C.A. Spitzer K.A. Clark C.C. et al.Low molecular weight heparin and aspirin for recurrent pregnancy loss: results from the randomized, controlled Hep ASA trial.J Rheumatol. 2009; 36: 279-287Crossref PubMed Scopus (271) Google Scholar and thus, there are currently no randomized trials evaluating the benefits of heparin and aspirin in women with recurrent miscarriage and true APS. A recent American College of Obstetricians and Gynecologists practice bulletin on APS does not support screening for anticardiolipin antibodies in patients with severe preterm preeclampsia or FGR but recommends screening those patients with 1 fetal loss or 3 or more recurrent embryonic losses. It also recommends the prophylactic use of heparin and aspirin in subsequent pregnancies in such women. However, such recommendation is not evidence based. Because the potential benefits of treatment are uncertain, screening such women is very costly and is associated with anxiety, and treatment is associated with side effects that can be severe. At present, data from relevant literature suggest that the association of anticardiolipin antibodies with recurrent miscarriage and placental insufficiency is weak at best. There are no evidence-based studies to indicate that treatment with prophylactic doses of heparin plus aspirin are beneficial. Thus, there is an urgent need for a multicenter trial with adequate sample size. Such trials will hopefully provide conclusive evidence-based treatment to replace recommendations based on personal bias.