Wimbledon has started in a blaze of sunshine. What a wonderful summer we are having (at least here in the South-East) – surely it can’t go on. June was, for me, “Midlands Month”. A lecture on Hughes syndrome, lupus and Sjogren’s to the annual meeting of The Royal College of GPs – this year in Birmingham. A very positive meeting – 300 GPs, with an extremely lively question and answer session.
Then off to Leicester to a meeting of research technicians, involved in updating and improving testing for antiphospholipid antibodies. It took me back to the early 1980’s when we first described what we initially called the ‘anticardiolipin syndrome’.
My technician, Chris Bunn, who with Dr Aziz Ghavari, and later, Nigel Harris, worked on developing an assay for the syndrome, recently reminded me that reason we used cardiolipin for the assay (rather than any other phospholipid) was because we had a jar of it in the lab. Such are the sometimes mundane stories behind scientific discoveries.
Talking about reminders, my colleague, Professor Munther Khamashta, regularly reminds me that we would all have become millionaires if we had patented the test instead of merely publishing it!
I am pleased that our new international charity is nearly ready to go (we are in the final stages of certification of a website and approaching doctors from around the world.) Our sole aim is the global education both of doctors and of the general public about Hughes syndrome/antiphospholipid syndrome (‘sticky blood’ – a common yet still under-recognised condition). For my part, I will, hopefully, continue to produce monthly updates, such as my blog, “Patient of the Month”, printed here.
Patient of the Month
“About the Family”
As medical students, we are taught that at the end of every “history taking”, there is a section called ‘Family History’
Obviously in Hughes syndrome, it is appropriate to ask about thrombosis, or, in women, recurrent miscarriage. But there is more to it than that…
Mrs JD, aged 36, was thought to have a form of multiple sclerosis (MS). Over the preceding 2-3 years she had developed a number of complaints including balance problems, fainting attacks, pins and needles in the legs (with fluctuating leg weakness) and occasional bladder disturbance.
Since her early teens, she had been prone to frequent headaches – often with migraine and episodes of fainting (including at school assembly). She had had 2 successful pregnancies, but had also had 2 early miscarriages. In her family there had been a history of ‘autoimmune’ problems, including thyroid, coeliac and (her mother) lupus.
She was referred to a neurologist who felt that MS was a possible diagnosis, but that there was some doubt in her mind. She did, however, consider the possibility of Hughes syndrome. Of the 3 commonly used tests, only one – anticardiolipin – was positive (IgM aCL at 36 units – ‘medium’ positive only).
Not much to go on. Certainly not from the tests. No thrombosis. Two miscarriages – not enough to meet the ‘criteria’ of 3 miscarriages.
Common problems – migraine, fainting in school, pins and needles – even, to an extent, multiple sclerosis. Perhaps the family history here was significant?
Could this be Hughes syndrome/antiphospholipid syndrome?
She decided to follow her hunch and the advice of colleagues, and treat the patient – firstly with aspirin – slight improvement only.
The neurologist of course felt concerned about starting a ‘difficult’ medicine such as warfarin in this patient. Such a big decision. In the event, she elected to try a 3-week course of heparin – a ‘clinical trial’. Safe medicine (low molecular weight (LMW) heparin) is now widely used in pregnancy clinics dealing with Hughes syndrome patients, and often provides guidance as to whether more ‘permanent’ medication such as warfarin might be considered.
The result was clear-cut. Improvement. Mrs J.D. was then started on Warfarin (attending anticoagulant clinic but also with self-testing).
That was 6 years ago. The patient remains well and symptom-free.
What is this patient teaching us?
At least ten possible lessons:
Relationship to MS?A number of patients with Hughes syndrome have neurological features which suggest MS. At present, this is a difficult topic, not least because few large scale studies have been reported. If we look at patients attending MS clinics, we are not certain whether the Hughes syndrome patients constitute 1% or 5%, or more. Hopefully, time will tell. Non-thrombotic manifestations of APS?At medical meetings, we often talk about “non-thrombotic” manifestations of Hughes syndrome. And in Mrs J.D’s medical history, there are certainly some of these, including migraine, balance problems and miscarriages (“only 2”). But not enough for a convincing diagnosis of Hughes syndrome. I really can’t emphasis this enough. Even in our original description of the syndrome 35 years ago, there were more ‘non-thrombotic’ features than obvious blood clots. “Only” 2 MiscarriagesI have ‘gone on’ about the requirement for 3 or more miscarriages for classification of APS. But ‘classification’ is a long way from diagnosis. The presence of migraines, other features and the family history of autoimmune disease should point to earlier testing. ‘Only’ one Test PositiveIn a busy clinic, test results vary wildly from patient to patient. While statistically linked to more aggressive disease, the clinical picture, in my view, carries more weight. In Mrs J.D.’s case, a single positive aPL test is significant. Fainting attacksIn recent years, reports have linked Hughes syndrome with another condition, called POTS, in some cases. POTS stands for paroxysmal tachycardia syndrome: or, in plain English, fainting and a fast heartbeat on standing up. (Often these patients’ histories go back to episodes of fainting in school). The condition is due to problems with the autonomic (internal) nervous system – another example of the targeting of the nervous system in Hughes syndrome.Double jointednessAnd to broaden the picture further, POTS is, in some patients, associated with ‘double jointedness (a condition broadly described as ‘Ehlers-Danlos’ syndrome). The ripples of Hughes syndrome spread even wider.The FamilyI have written about the importance of taking a family history. Some diseases have a strong genetic tendency. And autoimmune diseases as a group often appear to “run in families”. The questions shouldn’t be solely about clotting or miscarriage, but should include family histories of thyroid, lupus, MS and rheumatoid arthritis – and, of course, about Hughes syndrome and features such as migraine, balance problems and epilepsy, to name but three.Aspirin versus WarfarinDespite years of research and clinical experience, we are still not totally clear why aspirin is successful in some, yet not in others. There are, of course, a number of theories and published data on aspirin resistance – but in the vast majority of patients, aspirin response is a matter of trial and error.Heparin ‘trial’If aspirin isn’t helping, and the symptoms such as severe headaches are getting worse, where next? Some years ago, I published an article on the “Heparin trial”. In patients such as Mrs J.D. where the burden of illness is becoming intolerable, I have suggested a trial of 2-4 weeks (depending on response) Heparin injections using low molecular weight (LMW) heparin (which has replaced ‘old’ heparin because of its good safety profile). In some cases, there is a clear therapeutic response, for example, the disappearance of headaches. This very practical ‘therapeutic trial’, while seeming rather ‘clinical’ has, in my experience, proved very valuable in the assessment of many of these difficult Hughes syndrome cases.Warfarin: self-testing of INRMany of my patients have found huge benefit in INR self-testing – usually in collaboration with the patient’s coagulation clinics. It is a topic which sometimes generates heat and even half-truths – for example, that the lupus anticoagulant in the blood messes up INR testing – or that INR machines are inaccurate.
Remember how self-testing in diabetics opened up their world?
I believe that while we are stuck with Warfarin, self-testing of the INR level – especially in those (many) Hughes syndrome patients whose blood thickness (INR) is so volatile, can prove a potentially stabilising factor in these patients’ lives.
My apologies for the ‘shopping list’. These are the day-to-day topics that surface in a busy clinic. Far removed, perhaps from a textbook description of Hughes syndrome – but topics which matter to the patient.
Professor Graham R V Hughes MD FRCP