[show abstract][hide abstract] ABSTRACT: 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.RESULTSThe 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.
Human Reproduction Update 06/2013; · 9.23 Impact Factor
[show abstract][hide abstract] ABSTRACT: Venous thromboembolism (VTE) is effectively treated with anticoagulant therapy. After an initial treatment phase, extended treatment is effective to prevent recurrence after a first event but this is at the expense of a continued risk of bleeding. Ideally, patients at a high risk of recurrence and low risk of bleeding continue anticoagulant therapy, and for those at low risk of recurrence the duration of treatment can be limited. Identifying these patients, however, is difficult. Duration of treatment after a first VTE provoked by a transient risk factor should be limited to 3 months. Although guidelines suggest extended treatment for all patients after unprovoked VTE unless bleeding risk is high, we emphasize that the long-term risks of recurrent VTE off anticoagulation are uncertain whereas the risk of bleeding associated with anticoagulant therapy increases with age. In the absence of evidence of replaced mortality or improved quality of life with extended anticoagulant treatment, we suggest a limited duration for most patients after a first VTE. Extended treatment can be considered, based mainly on patient preference.
British Journal of Haematology 06/2012; 158(4):433-41. · 4.94 Impact Factor
[show abstract][hide abstract] ABSTRACT: Approximately 1-5% of women trying to conceive experience recurrent miscarriage, and in 50% of these women, the cause of the preceding miscarriages is unknown. Inherited thrombophilias such as factor V Leiden mutation, prothrombin gene mutation (PT 20210A), and deficiencies of natural anticoagulants protein C, protein S, and antithrombin are associated with recurrent miscarriage. Knowledge of the association between inherited thrombophilia and recurrent miscarriage and of potential treatment options for improving chances of a live birth could tempt physicians to test for inherited thrombophilia in women with recurrent miscarriage. However, the strength of the association between inherited thrombophilia and recurrent miscarriage is not very strong, and more importantly, no evidence indicates that the use of anticoagulants improves the chance of live birth in these women. With the current state of evidence, testing for inherited thrombophilia should not lead to altered clinical management and therefore, should not be performed routinely in women with recurrent miscarriage but only in the context of scientific studies.
Seminars in Reproductive Medicine 11/2011; 29(6):540-7. · 3.21 Impact Factor