Thrombophilia and pregnancy complications: cause or association?

Summary.  Both acquired and inherited thrombophilia is associated with an increased risk of pregnancy failure (i.e. sporadic and recurrent miscarriage, late fetal loss), as well as hypertensive pregnancy complications such as pre-eclampsia and HELLP syndrome. The question of whether this relationship can be considered causal is rather philosophical. For practical purposes, the consistency and strengths of associations, potential mechanisms and, most importantly, the possibility to intervene with anticoagulants are reviewed. Relevant methodological issues in the case of thrombophilia and pregnancy complications consist of differences between observational and experimental research and quality issues in randomized controlled trials. The mechanisms associating thrombophilia and pregnancy complications are likely to involve effects on trophoblast differentiation rather than mere hypercoagulability. Therapeutic options comprise aspirin as well as (low molecular weight) heparin. For women with antiphospholipid antibody syndrome, this treatment is often suggested although the evidence is limited. For women with inherited thrombophilia and unexplained recurrent pregnancy loss, at present there is no evidence supporting treatment. Observational research is hampered by severe methodological flaws or inconsistent results. Two published randomized trials have not used an adequate comparator (i.e. no treatment or placebo). Currently, randomized controlled trials with no treatment or placebo are being carried out and results should be awaited before implementing a potentially harmful intervention in pregnant women with inherited thrombophilia and a history of pregnancy complications.