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For the first time, low-molecular
weight heparin has been
shown to improve maternal
endothelial function in
pregnant women at high risk
of developing preeclampsia,
possibly mediated through
increased placental growth
factor bioavailability, reported a
randomised, prospective trial at
AHA 2016.
J
ohn Kingdom, MD, of Mount Sinai
Hospital, Toronto, Ontario, Canada,
explained that preeclampsia is a
hypertensive disorder of pregnancy
characterised by new-onset hypertension with
evidence of organ injury. The disorder affects
2–8% of pregnancies worldwide.
The majority of women with preeclampsia
present clinically near term with favourable
maternal and infant outcomes. A subset,
however, develop severe disease characterised
by the need for preterm delivery, typically
before 34 weeks of gestation due to end-
organ injury, severe hypertension, or
intrauterine growth restriction. Women with
severe preeclampsia demonstrate significant
cardiovascular impairment during pregnancy
and the immediate postpartum period, as well
as a higher risk of cardiovascular disease later
in life.
Given the significant short-and long-
term maternal cardiovascular effects of
preeclampsia, elucidating its pathogenesis has
been of interest in recent years. Yet the most
effective pharmacologic therapy to prevent
preeclampsia in screen-positive women
beyond aspirin has not been established.
Clinical symptoms typically resolve only on
delivery.
Low-molecular-weight heparin has been
evaluated for the prevention of various
placenta-mediated pregnancy complications,
including severe preeclampsia and recurrent
miscarriage. Multiple trials and systematic
reviews have concluded that low-molecular-
weight heparin reduces the incidence of
recurrent severe preeclampsia in high-
risk women, as well as perinatal mortality,
preterm birth, and infant birth weight <10th
percentile for gestational age. Others have
demonstrated no treatment effect.
As the majority of trials have consisted of
clinical endpoints, the mechanism of action
of low-molecular-weight heparin for the
possible prevention of severe preeclampsia
is unknown. Evidence suggests that observed
beneficial effects do not result from heparin’s
anticoagulant actions within the placenta.
An alternative hypothesis is that low-
molecular-weight heparin exerts vascular
actions in the maternal compartment.
These actions are thought to reverse the
systemic vascular dysfunction characteristic
of preeclampsia. Trials in patients with
coronary artery disease have determined that
low-molecular-weight heparin demonstrates
beneficial endothelial effects, possibly
through increased bioavailability of nitric
oxide.
Dr Kingdom and colleagues set out to
investigate the cardiovascular effects of low-
molecular-weight heparin in pregnant women
at high risk of preeclampsia.
Twenty-five pregnant women at high risk
of preeclampsia and 20 low-risk pregnant
controls at 22–26 weeks of gestation
underwent baseline cardiovascular
Low-molecular-weight
heparin improves
endothelial function in
pregnant women at high
risk of preeclampsia
PRACTICEUPDATE CARDIOLOGY
AMERICAN HEART ASSOCIATION ANNUAL SCIENTIFIC SESSIONS
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