Hughes Syndrome – Sticky Blood, Obstetrics and the GP

Dr Hughes first became interested in the syndrome that now bears his name in the early 1970s, when studying systemic lupus erythematosus (SLE). In 1983, he gave the Prosser-White Oration, in which he described women with multiple thromboses, neurological disease, thrombocytopenia, livedo reticularis, headaches, migraine, epilepsy, chorea, multiple abortions, peripheral thrombosis, Budd Chiari syndrome and early death from stroke. Many were thought to have 'lupus' but had negative antinuclear antibody tests. The diagnosis was changed to anti-phospholipid syndrome when it was found they had anti-phospholipid antibodies, then was renamed Hughes syndrome when Dr Hughes' part in discovering it was recognised.

It is often unrecognised. Of 146 women with primary stroke, 7% had anti-PL antibody. In 55 Italian people under 45 years old with strokes, 20% had anti-PL syndrome: four of the ten went on to have further strokes.

Dr Hughes has a weekly clinic of 800 patients, many of whom complain of memory loss. Many know precisely when their INR has fallen, because their dysarthria or headache returns when it falls from 3.2 to 2.9. One sufferer, an author, needs an INR of 3.4: if it falls to 3.1 she writes nonsense.

Some patients develop myelopathy from thromboses in the spinal cord, and are labelled as having multiple sclerosis. Of 27 patients originally diagnosed as MS half had had previous APS-related symptoms: when given warfarin 14 of the 16 primary APS patients had no further symptoms

Common features include teenage migraine, memory loss, accelerated atheroma, impotence (it affects men too), skin ulcers, mitral valve disease, monocular vision loss, and necrosis of the hip with steroids. Potentiating factors in APL and thrombosis are the oral contraceptive and smoking.

Much of the data comes from pregnancy, in which abortion and miscarriage are associated. A British Medical Journal review (1997; 314: 244) of pregnancy in Hughes syndrome patients concluded that aspirin was a big advance. Of 47 APS patients in whom the previous 60 pregnancies had a live birth rate of 29%, it became 70% when treated with aspirin and/or heparin.

Anti-phospholipid syndrome (APLS), said Dr Hughes, is the most common preventable cause of recurrent miscarriage. Women with it should take aspirin alone when they have no previous thrombosis, and aspirin with heparin when they have a previous miscarriage history. It causes up to 1 in 5 of all strokes in under 45s: with aspirin they are all potentially preventable. Some people with diagnoses of Alzheimer's, multiple sclerosis or rheumatic disorders may have APLS, and be treatable.

APLS has revolutionised the management of lupus. Some women with multiple infarctions can be taken off their high dose steroids with multiple infarctions. In fact if the treatment could have been given to Queen Anne, who had 17 miscarriages and no surviving heir, and had several other symptoms of APLS, she might have had an heir. That would have kept the Stuarts on the throne, and the House of Hanover would not have taken over. Our history would have been very different – George III might never have become King and we might still have America as a British Colony!