Abstract

There is a paucity of strong evidence associated with adverse pregnancy outcomes and thrombophilia in pregnancy. These problems include both early (recurrent miscarriage) and late placental vascular-mediated problems (fetal loss, pre-eclampsia, placental abruption and intra-uterine growth restriction). Due to poor quality case-control and cohort study designs, there is often an increase in the relative risk of these complications associated with thrombophilia, particularly recurrent early pregnancy loss, late fetal loss and pre-eclampsia, but the absolute risk remains very small. It appears that low-molecular weight heparin has other benefits on the placental vascular system besides its anticoagulant properties. Its use is in the context of antiphospholipid syndrome and recurrent pregnancy loss and also in women with implantation failure to improve live birth rates. There is currently no role for low-molecular weight heparin to prevent late placental-mediated complications in patients with inherited thrombophilia and this may be due to small patient numbers in the studies involved in summarising the evidence. There is potential for low-molecular weight heparin to improve pregnancy outcomes in women with prior severe vascular complications of pregnancy such as early-onset intra-uterine growth restriction and pre-eclampsia but further high quality randomised controlled trials are required to answer this question.

Highlights

  • Pregnancy alters the haemostatic system into a hypercoagulable state, which increases throughout pregnancy and is maximal around term

  • Fibrinolytic activity is reduced with plasminogen activator inhibitor type 1 (PAI-1) levels increased by five-fold and increases in placentally-derived plasminogen activator inhibitor type 2 (PAI-2), during the third trimester [3]

  • The FRUIT randomised controlled trials (RCTs) found that adding low molecular weight heparin (LMWH) to aspirin before 12 weeks gestation reduced the risk of recurrent early onset pre-eclampsia in women with inherited thrombophilia and prior delivery for pre-eclampsia/fetal growth restriction before 34 weeks [41]

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Summary

Introduction

Pregnancy alters the haemostatic system into a hypercoagulable state, which increases throughout pregnancy and is maximal around term. Fibrinolytic activity is reduced with plasminogen activator inhibitor type 1 (PAI-1) levels increased by five-fold and increases in placentally-derived plasminogen activator inhibitor type 2 (PAI-2), during the third trimester [3] These changes in the haemostatic system act as a physiological “safety net” for the peripartum period, but can predispose both the mother and fetus to complications during the pregnancy. Biological studies have demonstrated that heparin has other beneficial effects on the placenta in addition to the anticoagulant properties mediated through its interaction with antithrombin These include increased tissue factor pathway inhibitor, angiogenesis on the antiphospholipid antibody-inhibited human endometrial endothelial cell, and reduced trophoblast apoptosis, complement activation and platelet aggregation [6]

Inherited Thrombophilias
Acquired Thrombophilia
Biological Plausibility for Low Molecular Weight Heparin Use
Early Pregnancy Complications
Late Pregnancy Complications
Management
Findings
Conclusions
Full Text
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