Reducing miscarriage in women with antiphospholipid syndrome

A clinical trial funded by Versus Arthritis showed that treatment with aspirin and heparin significantly reduces the likelihood of miscarriage in women with antiphospholipid syndrome, enabling hundreds of women each year to have healthy pregnancies.

Antiphospholipid syndrome (APS), sometimes called sticky blood syndrome or Hughes syndrome, can cause blood clotting in the arteries and veins.

APS can occur on its own or alongside an autoimmune condition called lupus, and is a major cause of recurrent miscarriage as well as being one of the most common causes of stroke among people under the age of 40.

In people with APS, the immune system produces harmful antibodies called antiphospholipid antibodies (aPL), which attack proteins in the body and cause the blood to become sticky and more likely to clot. This can cause problems in pregnancy:

• In early pregnancy, these antibodies can stop the embryo embedding in the womb properly, increasing the likelihood of miscarriage.
• In later pregnancy, the antibodies may cause blood clots in the placenta, which can result in poor growth, pre-eclampsia or still birth.

aPL are detected in approximately 15% of women who experience recurrent miscarriages, defined as three or more miscarriages.

Without treatment with drugs, the live birth rate among women with recurrent miscarriages with aPL is estimated to be as low as 10%.

During the 1980s, treatment with aspirin, with or without steroids, to prevent recurrent miscarriage was largely based on anecdotal evidence.

At this time, Professor Lesley Regan, who was running the Recurrent Miscarriage Service at St Mary’s Hospital in London, successfully treated several pregnant women with aspirin and heparin.

In 1992, we funded Professor Regan to carry out a clinical trial to compare the impact of aspirin alone or a combination of aspirin and heparin on preventing miscarriage in APS.

The trial included 86 women who had experienced three or more miscarriages in their first or second trimester and tested positive for aPL. All women took aspirin following a positive pregnancy test, and after an ultrasound were randomly allocated to receive either aspirin alone or aspirin plus heparin up until 34 weeks of pregnancy.

The trial found that women taking aspirin plus heparin had a 71% live birth rate compared to a live birth rate of 42% for women taking aspirin only.

As a result of this trial, the UK Royal College of Obstetricians and Gynaecologists (RCOG) asked Professor Regan to write its guidelines on the investigation and treatment of couples with recurrent miscarriage. These guidelines recommend the use of aspirin plus heparin for women with recurrent miscarriage with aPL.

The trial findings – along with those of similar clinical trials – also informed guidelines in the US, Netherlands, and Australia, all of which recommend the use of aspirin plus heparin for women with recurrent miscarriage with aPL.

Many women with APS who would previously been unable to have children have now had successful pregnancies as a result of this research. Professor Regan’s clinic at St Mary’s Hospital is now the largest recurrent miscarriage clinic in Europe and receives approximately 1,000 referrals a year for couples from across the UK.

One of our volunteers, Jane Taylor benefitted from this research: “Research funded by Versus Arthritis has had a huge impact on my life. You could say it gave me my three children, as research supported by the charity in the 1990s led to the successful treatment I received for antiphospholipid syndrome which causes recurrent miscarriage.”

It’s estimated that 1% of women trying to conceive – equivalent to approximately 6,000 per year in the UK - experience recurrent miscarriage. As 15% of women with recurrent miscarriage test positive for aPL, this suggests that hundreds of healthy pregnancies may occur as a result of this treatment every year in the UK.