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Resources for Patients



Women with placental dysfunction are known to be at increased risk of experiencing an adverse outcome during their pregnancy.  These outcomes can include preterm birth, pre-eclampsia (problems with blood pressure), poor fetal growth during the pregnancy (known as intrauterine growth restriction; IUGR) and in some severe cases, death of the baby, particularly in the last trimester of birth (also called stillbirth). These adverse outcomes may be related to blood clotting in the placenta, resulting in placental damage and dysfunction.

What is a blood clot?
A blood clot (or thrombus) is the product of aggregated blood cells (platelets). It is a normal process in response to injury, but abnormal clotting can cause a thrombosis, where the thrombus blocks the blood vessel and obstructs blood flow. If this occurs in the blood vessels of the placenta, blood flow to the placenta (and therefore to the baby) is reduced. Without adequate blood flow, the placenta does not receive enough oxygen and nutrients, and areas can become damaged and die. This results in the inability of the placenta to provide enough oxygen and nutrients to support the growing baby.

What is heparin?
Heparin is a medication that reduces the ability for blood to clot.  It is routinely used in the care of pregnant women with a thrombophilia disorder (women whose blood clots more frequently, putting them at higher risk of developing a thrombosis).

How can heparin help?
Results from the HEPRIN trial will help us determine if administration of heparin to women who display signs of placental insufficiency
can reduce the risk of adverse pregnancy outcomes and improve maternal and infant health.  Placental insufficiency is determined through abnormal results in two or more of the following categories:

  1. Maternal serum biochemistry

  2. Uterine artery Doppler

  3. Placental morphology

See Placental Testing for more information on these tests.

Normal Placental Function

Normal placental function is determined by appropriate levels of biochemical markers in maternal blood, a long, thin placenta with homogenous texture, and adequate blood flow from the mother to the placenta (shown below).

Normal Placenta Function Schematic

© Leslie Proctor, 2009

Placental Insufficiency

Placental insufficiency is diagnosed when there is elevated (AFP, hCG, or inhibin) or low (PAPP-A) levels of these proteins in maternal blood, a small, thick placenta with areas of damage, and reduced maternal blood flow to the placenta.  These parameters are assessed by 22 weeks.  If these abnormalities are noted and placental insufficiency is diagnosed at this time, the baby has likely not experienced any consequences of this disease (i.e. the baby is still growing at an appropriate rate). For this reason, in the diagram below the developing baby is drawn at a normal size, despite maternal markers of placental insufficiency.

 Uteroplacental Vascular Insufficiency

© Leslie Proctor, 2009

However, as the pregnancy continues, the consequences of placental insufficiency begin to impact the developing baby.  Eventually, the placenta is unable to meet the oxygen and nutrient demands required to sustain normal fetal growth and development.  So, the developing baby uses the available oxygen and nutrients to stay alive and to maintain brain oxygenation, and reduces its rate of growth. During this time, ultrasound monitoring is used to see how the developing baby is coping with these effects of placental insufficiency.  This plan of ultrasound monitoring is designed to prevent the possibility of stillbirth, which occurs where the placental oxygen and nutrient supply to the developing fetus is less than what is required to survive. The woman is at risk of developing other adverse pregnancy outcomes, including pre-eclampsia and early delivery (pre-term birth).

placental damamge causing IUGR

© Leslie Proctor, 2009

Potential Benefit of Heparin Therapy

Although we cannot prevent placental insufficiency, we believe heparin treatment may be able to:

  • Prevent or delay worsening placental function


  • Prevent or delay the onset of consequences associated with the disease (pre-eclampsia, IUGR, and stillbirth).  

By delaying the onset of these disorders, the gestational age of the baby at birth is prolonged, resulting in an increased chance of survival and decreased risk of complications.

Heparin treatment of UPVI

© Leslie Proctor, 2009

Therefore, heparin therapy may prevent the progression of placental insufficiency throughout the pregnancy, resulting in better outcomes for both mother and baby.

Patient FAQs

What is a randomized controlled trial?

A randomized controlled trial (RCT) is a scientific procedure commonly used in testing medicines such as heparin.  RCTs involve allocating treatments to subjects at random. This ensures that the different treatment groups are 'statistically equivalent'.

How will my treatment be chosen?

A random assignment of patients to any of the groups, with precautions taken to ensure that the group assignment of patients are not revealed to the study investigators prior to definitively allocating them to their respective groups.

What will happen if I am randomized to the control group?

Traditionally, the control in a randomized controlled trial refers to a group of patients who do not receive the treatment under study.  The control group gives investigators important clues to the effectiveness of the treatment, its side effects, and the parameters that modify these effects.  If you are randomized to the control group, you will receive the same high standard of care as those patients randomized to the heparin group.

Can heparin affect my baby?

Heparin does not cross the placenta.  When heparin enters your bloodstream, it will be circulated through the blood vessels of the placenta but will not be transmitted to your baby.  Therefore, heparin will not affect your baby.

Is heparin safe to use in pregnancy?

Heparin  has been used extensively during pregnancy for women who are at increased risk of clotting problems (women with a thrombophilia disorder), and is safe to use in pregnancy.  It has not been demonstrated to have any effect on the occurrence of fetal anomalies, it does not significantly alter bone mass during pregnancy, and the theoretical risk of placental bleeding is very rare.

How do I administer heparin?

Heparin is administered by twice daily subcutaneous injections. This means that a small amount of the drug (0.3 mL) is injected under the skin.  The skin most easily accessed is around the abdomen and hips.  See the heparin injection techniques for more information.

What are the risks associated with using heparin?

Some women find injections of heparin to be uncomfortable due to skin bruising. This is temporary and disappears after stopping the medication. Other uncommon side effects include:

  • A reduction in your platelet count (platelets are a component of the blood that help in clotting) which occurs in less than 1% of women taking heparin for more than 6 months. If randomized to receive heparin, you will have your platelet count measured every two weeks.
  • The possibility of bleeding into the placenta, which occurs in less than 0.04% of women taking heparin in pregnancy
  • Very rarely there may be a reduction in bone density and risk of bone fracture, although this is more a theoretical than an actual risk, which occurs in less than 1% of women who need to take heparin for more than 6 months duration.

Downloadable resources

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Funding for HEPRIN is provided by the Physicians' Services Incorporated Foundation