APS in Pregnancy

Professor Catherine Nelson-Piercy

Guy’s and St. Thomas’ Hospitals Trust

Antiphospholipid syndrome (APS) affects women of child-bearing age and is commonly encountered in obstetric practice.  Pregnancy poses an important challenge for health care professionals caring for these women. Pre-conception counselling with stratification to differentiate the phenotypes of obstetric APS is important as this determines risk and management.

APS may present with adverse pregnancy outcome. aPL target the placenta by binding β₂-glycoprotein I (β₂ GPI) on the trophoblast. Both thrombotic APS and lupus anticoagulant are markers for adverse pregnancy outcome. A relevant clinical history should prompt screening for anticardiolipin antibodies (aCL) and lupus anticoagulant (LA), which if positive should be repeated 12 weeks later. It is important to take a detailed obstetric history as not all losses are typical for APS and it is equally important not to label women with APS who only have aPL. Stratification of the aPL profile into high / medium / low risk is also important for determining management. The recently published ACR/EULAR APS classification criteria, designed primarily for research, use an evidence based weighting system for both laboratory and clinical criteria.

Women diagnosed with APS based on 3 or more early pregnancy losses (weighting 1) have a reduced risk of subsequent pre-eclampsia and preterm delivery compared to women with a previous history of early onset pre-eclampsia with or without fetal loss (weighting 3) or previous venous thrombosis (weighting 1 or 3 depending on whether and how provoked).

The EULAR recommendations for management of APS will be discussed. Women with thrombotic APS are managed with LMWH in pregnancy and obstetric APS is managed with low dose aspirin +/- LMWH. Paradoxically the evidence from randomized controlled trials supporting the use of low molecular weight heparin (LMWH) in addition to aspirin is lacking for women with early onset pre-eclampsia with or without evidence of placental insufficiency. This is in contrast to the numerous studies and systematic reviews addressing the use of aspirin with or without LMWH for women with APS diagnosed following recurrent early pregnancy losses. Hydroxychloroquine has been explored as a therapy in APS and a randomized trial is in progress.

References

1. Kim MY, Buyon JP, Guerra MM, et al. Angiogenic factor imbalance early in pregnancy predicts adverse outcomes in patients with lupus and antiphospholipid antibodies: results of the PROMISSE study. Am J Obstet Gynecol 2016;214(1):108.e1-08.e14.
2. Mekinian A, Lazzaroni MG, Kuzenko A, et al. The efficacy of hydroxychloroquine for obstetrical outcome in anti-phospholipid syndrome: Data from a European multicenter retrospective study. Autoimmun Rev 2015;14(6):498-502.
3. Schreiber K, Hunt BJ. Managing antiphospholipid syndrome in pregnancy. Thromb Res.2019 Sep;181 Suppl 1:S41-S46.
4. Soh MC, Pasupathy, D, Gray G, Nelson-Piercy C. Persistent antiphospholipid antibodies do not contribute to adverse pregnancy outcomes. Rheumatology 2013; 52:1642–7.
5. Tektonidou MG, et al. Eular recommendations for the management of antiphospholipid syndrome in adults. Ann Rheum Dis 2019;78:1296–1304. doi:10.1136/annrheumdis-2019-215213
6. Barbhaiya M, Zuily S, Naden R, et al. The 2023 ACR/EULAR antiphospholipid syndrome classification criteria. Arthritis & Rheumatology. 2023;75(10):1687-1702.
7. Yang Z, Shen X, Zhou C, Wang M, Liu Y, Zhou L. Prevention of recurrent miscarriage in women with antiphospholipid syndrome: A systematic review and network meta-analysis. 2021;30(1):70-79.