Reducing miscarriage in women with APS
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.
APS and pregnancy
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%.
Aspirin and heparin to prevent recurrent miscarriage
During the 1980s, treatment to prevent recurrent miscarriage was largely based on anecdotal evidence. Several case studies from the late 1980s reported the successful use of aspirin either alone or in combination with steroids to prevent miscarriage in women with APS. However, the use of steroids in pregnancy was associated with a range of side-effects including:
- high blood pressure
- premature birth.
At this time, Professor Lesley Regan was running the Recurrent Miscarriage Service at St Mary’s Hospital in London. She treated one patient who had aPL with aspirin and heparin, which resulted in a successful pregnancy. She then treated several other women – successfully – with aspirin and heparin.
In 1992, we awarded a project grant to Professor Regan to conduct a clinical trial to compare the impact of aspirin with aspirin plus 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. After an ultrasound to confirm the viability of the foetus, women were randomly allocated to receive either aspirin alone or aspirin plus heparin up until 34 weeks’ gestation.
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.
Changing the guidelines
The findings of the trial led to the UK Royal College of Obstetricians and Gynaecologists (RCOG) asking 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.
It’s estimated that 1% of couples trying to conceive – equivalent to 6,000 couples in the UK – suffer experience recurrent miscarriage. As 15% of women with recurrent miscarriage test positive for aPL, this suggests that hundreds of couples in the UK may be benefiting from this treatment each year.