Heparin in Human Placental Development and the Prevention of Placental Complications of Pregnancy

Abstract

The development of effective anticoagulant drugs available for use in pregnancy has resulted in dramatic improvements for a number of potentially life-threatening conditions. These include the treatment and prevention of venous thromboembolism and the thrombotic complications of antiphospholipid antibody syndrome, as well as the management of pregnant women with mechanical heart valves. The most commonly used class of drug includes heparin, a highly-charged macro-molecule that does not cross the placenta, in contrast to the potentially teratogenic and fetotoxic oral drug warfarin. This review will focus on our current lack of understanding of the wider actions of heparin and examines the possibility that large numbers of pregnant women are presently being treated inappropriately with heparin.

Low‐molecular‐weight heparin added to aspirin in the prevention of recurrent early‐onset pre‐eclampsia in women with inheritable thrombophilia: the FRUIT‐RCT

“…In the ongoing TIPPS trial, dalteparin, given in the same dosage as in the FRUIT study at least until 20 weeks and during the second wave of trophoblast invasion, did significantly increase plasma anti‐Xa activity, but had no significant effect on the coagulation activation markers: thrombin‐antithrombin complexes, prothrombin fragments 1 and 2, and D‐dimer concentrations [24]. The mechanisms of positive and negative influences of heparin on trophoblast invasion are increasingly studied and discussed [25]. The present data suggest that at least the first part of the second wave of trophoblast invasion can be supported by LMWH treatment, leading to reduced early‐onset HD.…”

Heparin promotes soluble VEGF receptor expression in human placental villi to impair endothelial VEGF signaling

“…Due to the high affinity of heparin to multiple proteins [1], it is possible that heparin disturbs the equilibrium of several growth factors and other molecules at the syncytiotrophoblast surface. The present experiments were confined to a commonly‐used LMWH in pregnancy.…”

“…Preeclampsia (PE) is a potentially life-threatening hypertensive disorder of pregnancy characterized by vascular dysfunction and systemic inflammation involving the brain, liver and kidneys of the mother [1]. Most cases that occur near term are relatively mild and are associated with a variety of maternal risk factors, while the more severe forms of preeclampsia begin during the second trimester and are associated with severe placental dysfunction, extreme preterm birth and perinatal handicap or death, and an increased risk of cardiovascular disorders [2].…”

Overview of low molecular weight heparin for preventative treatment of adverse obstetric outcomes related to abnormal placentation

“…The multiple effects of LMWH on placental development and our lack of their complete understanding have been reviewed . However, independently from the postulated mechanism(s) of action of LMWH, information gathered in vivo during an RCT of LMWH has shed indirect light on the effects of LMWH on placentation.…”