Although the most feared brain manifestations of Hughes Syndrome are stroke and TIA (transient ischemic attack), almost any neurological picture can be seen. Perhaps the 2 commonest features are headache, especially migraine, and memory loss.
Fear of stroke is the biggest worry in patients with Hughes syndrome; any sign of TIAs (‘transient ischemic attacks’) usually requires anticoagulant treatment.
Many patients with APS associated memory loss find that their memory problems markedly improve when blood thinning is started. Other ‘neurological’ features include seizures (now increasingly recognised as a problem in some patients with APS), chorea and other movement disorders, sleep disturbance, visual symptoms, and loss of sensation and balance problems. Not surprisingly, some patients are wrongly diagnosed as MS. We have recently reported a link in some Hughes Syndrome patients with autonomic nerve dysfunction. The autonomic nerves are those which supply the ‘internal’ organs such as the heart, gut, lungs, and sweat glands. Symptoms include a drop in blood pressure on standing and pulse rate irregularities.
Possibly the commonest feature is pulmonary embolism – lung clot. Usually acute chest pain and shortness of breath.
The clots can arise from a variety of sources, e.g. from the leg – a leg clot or ‘DVT’. This usually presents as an acute, painful swelling in the calf. The clot can occur at any time, and ‘out of the blue’, though it can occur after a long-haul flight, or after surgery, or in women starting on the ‘pill’.
Pulmonary embolism is usually acute, and often life threatening. In some patients frequent small, undiagnosed pulmonary emboli lead gradually to severe lung function impairment.
Angina is becoming recognised as a feature in a number of Hughes Syndrome patients.
Less common, but important, is a danger of blood clotting and damage to the heart valves.
Angina is becoming recognised as a feature in a number of Hughes Syndrome patients. Interestingly, the coronary arteries themselves may be clear, but the angina attacks can be very troublesome. Less common, but important, is a danger of blood clotting and damage to the heart valves.
One recent link is with a cardiac condition known as “Syndrome X”. This is a condition characterised by angina (chest pain) but with normal coronary arteries on angiogram. Presumably the angina pain results from sludging of the “sticky blood” rather than from diseased, narrowed arteries.
The recognition that Hughes Syndrome is an important and common cause of angina and other cardiac disturbances, especially in younger women (under 40) has led to a dramatic increase of the syndrome in the world of cardiology.
Impaired blood supply can affect abdominal organs such as the liver and bowel.
Impaired blood supply can affect abdominal organs such as the liver and bowel. One common symptom is “abdominal angina” – stomach pain coming on an hour or so after a (big) meal – just when digestive processes demand an increased blood supply.
Another gastro-intestinal feature (rare) is “ischemic colitis” – when the blood supply to areas of the bowel are cut off leading to the acute surgical emergency of bowel infarction.
Another abdominal organ which can become impaired in Hughes Syndrome is the liver. The effects can be ‘sub-clinical’ – for example abnormal blood “liver function” results on routine blood testing, through to severe, including clotting of liver veins (e.g. the “Budd-Chiari” syndrome) or arteries.
Clotting in the kidney artery can lead to a localised artery narrowing known as “renal artery stenosis” – a condition that can, in turn, lead to a raised blood pressure.
Clotting in the kidney vein is one of the causes of a heavy protein leak in the urine. Clotting in the kidney artery can lead to a localised artery narrowing known as “renal artery stenosis” – a condition that can, in turn, lead to a raised blood pressure.
In the 1 in 5 or so Lupus patients with APS/sticky blood, the presence of a protein leak can have different causes – inflammation in the patient with lupus nephritis, or thrombosis, an alternative diagnosis in the lupus patient who also has APS.
Interestingly, patients with Hughes can occasionally show a reduced platelet count.
Interestingly, patients with Hughes can occasionally show a reduced platelet count. Rarely, this can be dramatic – e.g. down to 10,000 (normal 150,000 to 200,000), but more often, “borderline low”, e.g. 90,000.
The fact that some patients with what is essentially a blood clotting illness (Hughes Syndrome) can become at risk from bleeding from severe thrombocytopenia (very low platelets) is both confusing and difficult to treat. Fortunately rare.
Bones and Joints
Hughes Syndrome patients often complain of joint pains.
Hughes Syndrome patients often complain of joint pains. Two particular features have been noted – an increased tendency to bone fracture (especially foot metatarsal fractures) and to attacks of hip pain. In rare cases, the hip(s) have developed degeneration – ‘avascular necrosis’. These attacks of hip pain may well be another example of ischemia – “hip angina” – secondary to blood sludging (and the hip pain attacks often improve with anticoagulation).
In a number of patients with APS and joint pains, the symptoms are due to a related condition – often Sjogren’s syndrome, sometimes lupus.
Involvement of the bones and joints has become better recognised in recent years, some patients suffering multiple bone fractures.
Antiphospholipid Syndrome (APS) is now recognised as the most common and treatable cause of recurrent miscarriages.
Antiphospholipid Syndrome (APS) is now recognised as the most common and treatable cause of recurrent miscarriages. Most, though not all, such cases appear to result from impaired circulation to the placenta. The risk of miscarriage is high, some women suffering a dozen or more miscarriages. Most, but not all, of these pregnancy losses are in the first 3 months, though, sadly, late pregnancy loses (stillbirth) can occur, as can ‘IUGR’ (intrauterine growth retardation).
At the other end of the spectrum, a number of our patients attend infertility clinics (in some, this may be down to recurrent, very early pregnancy losses). Before the wider recognition and treatment of pregnant women with positive anti-phospholipid (aPL) tests, the successful birth rate was under 20%. Now, in specialised centres, with the use of anticoagulation (most commonly aspirin and heparin) the successful birth rate is over 90%. It has been said that Hughes syndrome and the measurement of antiphospholipid antibodies in pregnant women has changed the face of obstetrics.
The more patients we see with the features of Hughes Syndrome, the more we recognise that the blood tests can sometimes prove negative. For example, a 30 year old woman with a history of 4 miscarriages, migraines, low platelets and a mini stroke (and, critically, a strong family history of Hughes Syndrome), might have negative tests.
Of course there are a number of possible explanations – the diagnosis could be wrong (unlikely in this patient), previously positive aPL tests may have now become negative or – most likely – we still need new and improved tests.
Several years ago, we labelled this syndrome ‘Sero-negative APS’. Very recently, an important review was published. Zohoury and colleagues ran a comprehensive battery of tests on 68 ‘sero-negative APS’ patients. Of these patients, 37% proved positive, using these additional ‘non-criteria’ tests.
The concept of sero-negative APS is one of the most important in the whole spectrum of Hughes Syndrome. Think of all additional patients who could be successfully treated.
Early on in our description of the antiphospholipid syndrome, we were referred a small number of patients with an acute illness – a “total collapse of a number of organs”.
The cause of what became known as CAPS – Catastrophic Antiphospholipid Syndrome – was unclear – but 2 precipitating factors appeared to be:
- An acute infection
- The sudden stopping of a patients routine anticoagulation treatment
This syndrome, characterised by widespread clinical thrombosis and “shut down” of multiple organs, was rare, but life-threatening – over one half of patients dying.
Thanks to increased awareness of the syndrome and its recognition in Intensive Care Units worldwide, the prognosis for CAPS is improving.
One major advance has been the setting up of an International ‘CAPS Registry’ by my colleague, Dr Ricard Cevera and his team in Barcelona – a vital information centre for pooling knowledge of this rare condition.