Antithrombotic treatment for pregnancy complications: which path for the journey to precision medicine?

Abstract

SummaryHaemostatic and vascular biology mechanisms appear to play an important role in the pathogenesis of placenta-mediated pregnancy complications. Although low-dose aspirin (LDA) has a modest effect in preventing preeclampsia, antithrombotic interventions, LDA and low molecular weight heparin (LMWH) have not definitively proven their effectiveness in women with placenta-mediated pregnancy complications selected by previous pregnancy outcome alone. Given the heterogeneous aetiology of placenta-mediated pregnancy complications, it is critical to stratify patients according to maternal and fetal characteristics and disease mechanisms rather than simply by pregnancy outcome, such as miscarriage. Such stratification could identify those who could benefit from antithrombotic interventions in pregnancy. We lack data on genome-wide association studies, biomarkers and trials of interventions applied to specific homogeneous populations. Future studies should focus on elaborating different disease mechanisms and examining antithrombotic interventions in specific and more homogeneous groups, such as thrombophilic women with well-characterized placenta-mediated pregnancy complications, stratified by disease severity and pathological findings. Because of fetal safety concerns with new anticoagulants, the intervention should focus on heparins alone or in combination with LDA. Thus, placentamediated pregnancy complications deserve precision medicine, defining disease by mechanism rather than outcome with interventions focused on a more personalized approach.

Low-molecular-weight heparin and aspirin use in relation to pregnancy outcome in women with systemic lupus erythematosus and antiphospholipid syndrome: A cohort study

“…LMWH probably has an early effect that may occur at cellular level, by decreasing trophoblast apoptosis and increasing the production of proteases involved in the trophoblast invasion of the maternal endometrium (23,24). In vitro studies have shown an effect of LMWH on angiogenesis in the placental villi and show an influence on the dysregulation of soluble vascular endothelial growth factor (25,26).…”

Antithrombotic therapy for pregnancy complications: let's not throw the baby out with the bath water

“…This resonates with other trials that also showed no general benefit, including the ALIVE trial, where LDA and LMWH were used in women with recurrent pregnancy loss with preconceptional LDA use 1. Thus, EAGeR and a number of other trials show no benefit from antithrombotic interventions starting either before or following conception.…”

“…Although there is no consistent benefit from antithrombotic interventions for pregnancy complications in these trials, others have reported positive results 1. Therefore, it is important to make a better assessment of where the treatment is best employed, based on biological plausibility for effectiveness, before rejecting antithrombotics for prevention of pregnancy complications.…”

Thrombosis and hemostasis health in pregnancy: Registries from the International Society on Thrombosis and Haemostasis

“…Those complications, such as preeclampsia, placental abruption, and birth of a small‐for‐gestational age neonate due to placental insufficiency and fetal death, remain leading causes of fetal‐maternal morbidity and mortality and are risk factors for maternal cardiovascular diseases . Effective preventive strategies and assessment of risk of recurrence do not currently exist . Controversy remains around the decision to perform thrombophilia testing or prescribe low‐molecular‐weight heparin.…”

“…Participants of recurrence do not currently exist. [4][5][6][7][8] Controversy remains around the decision to perform thrombophilia testing or prescribe low-molecular-weight heparin. This is mostly based on the opinion of the consulting expert and sometimes the patient's preference.…”