Education, Awareness, Support

May 2017

by Professor Graham R V Hughes MD FRCP

Waiting for a taxi to take me back to Basel airport for the short flight home to London. As good a time as any to start writing the May ‘blog’.

I have cut my travel this year – my only ‘away’ lecture this month was to Leeds…until this one-day meeting in the pretty little town of Freiburg in southern Germany. An interesting one-day symposium bringing together lab technicians and doctors with a special interest in connective tissue disorders. These included Pier Luigi Meroni from Milan – a leader in the field of Hughes syndrome, and an old friend with whom we have published many research papers.

One topic which came up was testing for Hughes syndrome in pregnancy – a topic which I am focussing on this month’s blog.

Pier Luigi and I discussed our new charity (GHIC) – the Graham Hughes International Charity – for me a very exciting project which aims to bring together doctors, other health workers and patients. We aim to link up with other patient groups on a global basis.

Hughes Syndrome and Pregnancy

A rather simplistic view of Hughes syndrome is that it consists of two features – thrombosis and abortion. Many of my previous blogs have tried to highlight some of the frequent “non-thrombotic” manifestations such as memory loss, seizure, migraines, ‘cold circulation’ and chest pains – symptoms more likely due to blood ‘sludging’ than outright thrombosis.

But, having said this, pregnancy problems (and successes) are a major part of the picture. Success, yes – but still with a long way to go.

Patient of the Month

Mrs Sally-Ann R., aged 25, had been trying for a pregnancy for over 3 years. Both she had her husband had been investigated for infertility. Apart from one episode of a suspected DVT following a holiday flight to Goa, there had been no major illness. The diagnosis of DVT (acute painful swelling of the left calf) was not confirmed, but was treated with aspirin and lots of rest during her holiday in Goa.

In the family history, thyroid problems featured largely, but Mrs R’s thyroid tests were normal.

And then, perhaps unexpectedly, she became pregnant. Sadly, for only 3 months, when she miscarried. Some months later, a second pregnancy – and a second miscarriage. After a third 3-month miscarriage, she started a course of daily low dose aspirin 75mg, recommended by friends. And this seemed to work – this time, the pregnancy progressed – only to end tragically at 8 months with a stillbirth.

At long last Mrs R was tested for aPL (antiphospholipid antibodies). Two out of the 3 tests showed positive.

At this point, her fortune changed for the better. She was referred to specialist ‘lupus pregnancy’ clinic and treated through the whole of the next pregnancy with both aspirin and heparin. Success. With similar treatment, Mrs R now has two healthy children...

...Ten years on Mrs R started to complain of frequent headaches and ‘funny turns’. Neurological investigation (including brain MRI) was normal, as were her blood tests, though her aPL remained positive – unchanged from their titre 10 years earlier. How would you treat? And, equally critically...

...What is this patient teaching us?

The past 30+ years have witnessed dramatic improvements in pregnancy outcome in Hughes syndrome. Before 1983, the pregnancy success rate in aPL positive women was a dreadful 15-20% - some women suffering 10 or more pregnancy losses. Now, in most large obstetric units dealing with Hughes syndrome, the success rate is over 90%. This is largely due to 3 factors – early diagnosis (aPL blood tests in early pregnancy), treatment (aspirin or aspirin and heparin), and knowledgeable obstetric management especially in late pregnancy.

(1) An editorial in The Times in 2012 entitled “The Stillbirth Scandal” raged against the poor figure regarding stillbirths in the UK. “Every day, as many as 3 babies are stillborn who could have lived”

(2) In a recent article in LUPUS, Dr Ware Branch and his outstanding team in Salt Lake City reported positive aPL tests in 9.6% of stillbirth cases

(3). So - a simple blood test, proven preventative treatment – why the delay?

All is not well – take the case of Mrs R. A few years ago, we ran a survey of current practice in UK obstetric units. The findings were disappointing! Of the 11 UK hospital trusts, 5 did not include aPL testing in new pregnancies (my old hospital, St Thomas’, did not include aPL in pregnancy screening but did include syphilis!)

Why is this? Costs of course play a part – there are many causes of miscarriage other than Hughes syndrome – thus current committee advice is that aPL testing is only recommended after 3 miscarriages!

For this reason, I have suggested a simple 3-point questionnaire to highlight at-risk women, and which would take a few seconds in the midwife/obstetrician’s first pregnancy visit. They are:

  1. Have you had a thrombosis?
  2. Are you a migraine sufferer?
  3. Do you have a family history of autoimmune disease? (e.g. lupus, rheumatoid arthritis, MS, thyroid disease)

(2) In Mrs R’s case, with a strong family history of thyroid disease, and a possible (admittedly not proven) history of a leg clot, there would be sufficient reason, I believe, for the simple blood checks which could have saved so much tragedy.

Post-Script:

Ten years later: the headaches and ‘funny turns’. Possible Hughes syndrome? Needs treatment? Yes and yes.

Another of the lessons coming from patients such as Mrs R is that other manifestations of Hughes syndrome can come on years after the pregnancy history. Be prepared to make the diagnosis and to treat.

Professor Graham R V Hughes MD FRCP

Professor Graham R V Hughes MD FRCP

Head of The London Lupus Centre
London Bridge Hospital