Antithrombotic therapy for pregnancy loss

Paulien G. de Jong, Mariëtte Goddijn, Saskia Middeldorp

BACKGROUND Although an association between thrombophilia and pregnancy loss has been observed in many studies, little is known about the pathophysiological mechanisms behind this association. Considering the association between thrombophilia and pregnancy loss, the efficacy of antithrombotic therapy for women with pregnancy loss (with or without thrombophilia) has been studied for the past 30 years. METHODS We performed a comprehensive review of the literature on the strength of the association between thrombophilia and pregnancy loss, the pathophysiological mechanisms and the efficacy of antithrombotic therapy to increase the chance of live birth. RESULTS The association between pregnancy loss and thrombophilia varies according to the type of thrombophilia (e.g. antiphospholipid syndrome versus forms of inherited thrombophilia) and according to the type of pregnancy loss (single versus recurrent pregnancy loss and early versus late pregnancy loss). Thrombophilia may induce thrombosis in decidual vessels or impair placentation through hypercoagulability and inflammation, but these hypotheses need further verification. For women with antiphospholipid syndrome, evidence from small-sized trials suggests a beneficial effect of antithrombotic therapy but additional randomized controlled trials are essential to confirm this. Whether antithrombotic therapy increases the chance of live birth in women with inherited thrombophilia is unknown. Recent randomized controlled trials have consistently shown that antithrombotic therapy does not increase the chance of live birth in women with unexplained recurrent miscarriage. CONCLUSIONS There are large gaps in knowledge and a lack of evidence for treatment of women with pregnancy loss with thrombophilia. To provide a solid base for clinical practice, further studies on the role of coagulation in reproduction, as well as international collaborations in randomized controlled trials of antithrombotic therapy in women with pregnancy loss, and antiphospholipid syndrome or inherited thrombophilia are urgently needed.