Hughes syndrome (antiphospholipid syndrome)

Introduction

Often called sticky blood syndrome, this condition, in which the blood has a tendency to sludge or clot, was first described in detail a mere 36 years ago in 1983.

It is another cousin of lupus (ie, it is an autoimmune disease). In this case, the offending antibodies disrupt the membranes of the platelets and blood vessels resulting in thrombosis. These vital membranes consist of complex molecules such as phospholipids, and the title given to the syndrome was the antiphospholipid syndrome (APS). Such has been the explosion of knowledge of this syndrome that international conferences on APS are now held every second year. In 1992, Professor Graham Hughes was honoured that his colleagues recognised his discovery of the condition with the eponym Hughes Syndrome.

Main Features

Under normal conditions, blood does not clot. The blood cells and platelets flow cleanly along the veins and arteries like trout in a stream. In Hughes Syndrome sudden (or gradual, more subtle) clotting can occur, leading, for example, to thrombosis (clot) in an arm or leg, which is known as deep vein thrombosis (DVT).

This tendency to clotting can affect any part of the body, including delicate organs such as the brain. Many patients carrying antiphospholipid antibodies (aPL) are asymptomatic, the thrombosis only happening when other known risk factors are present (e.g. after a long-haul flight, starting in the oral contraceptive pill, pregnancy). The two, seemingly, most susceptible organs are the brain and, in pregnancy, the placenta.

Brain

Just as a car engine stutters when deprived of the correct mix of gasoline, so does the brain with sticky blood. Almost every neurological feature has been reported in Hughes syndrome, including fits, balance problems, visual disturbance (some Hughes syndrome patients are wrongly diagnosed with multiple sclerosis) and movement disorders. However, the two most prominent symptoms are headache and poor memory.

Headaches can start as early as childhood, and are often migrainous with nausea and flashing lights. There is often a family history of migraine.

Memory loss varies from mild (‘I couldn’t find the right words’) to severe (i.e. so much so that the patient often fears Alzheimer’s disease).

The most feared complication is stroke; it has been estimated that up to 1 in 5 of all strokes in people under 45 are due to Hughes syndrome. The good news is that these can be prevented.

Skin and other organs

Poor circulation in the skin leads to a mottled (corned beef skin) appearance called livedo reticularis.

In the heart, poor circulation can lead to chest pain (angina), in the lungs to shortness of breath, in the kidney to raised blood pressure and in the stomach to abdominal pain after meals. In the blood the platelet numbers can be reduced (thrombocytopenia).

Occasionally, clotting can become so widespread and acute, leading to a life threatening, very rare condition dubbed the catastrophic antiphospholipid syndrome.

Pregnancy

Clotting in the placenta can lead to impaired blood supply to the fetus, leading to miscarriage (or even late pregnancy loss). Indeed, Hughes syndrome has been called the most common treatable cause of recurrent pregnancy loss. Some women suffer six, eight, ten or even more miscarriages.

The diagnosis and treatment (with either aspirin or heparin) of Hughes syndrome has proved to be one of the success stories of modern medicine, with the successful pregnancy rate rising from 18% in 1985 to over 90% in modern lupus pregnancy clinics.

Infertility

In some women, recurrent very early pregnancy loss leads to a label of infertility. Indeed, many infertility clinics now routinely test for aPL, and some include heparin, for example, in their treatment protocol. However, the degree of contribution of aPL to overall infertility figures is unclear at the present time.

Diagnosis

· Anticardiolipin antibodies

· Lupus anticoagulant

Diagnosis is confirmed by two relatively simple blood tests, now carried out in laboratories throughout the world.

These blood tests have rather complicated (and confusing) names. The reason for needing to tick the box for two rather than one test is that a number of patients with Hughes syndrome are only positive for one or the other.

Treatment

Currently, there are three main choices: aspirin (75-100 mg daily or clopidogrel [Plavix®] for those intolerant of aspirin), heparin, and warfarin.

Aspirin is satisfactory for most milder cases, while warfarin is necessary for those with clear cut thrombosis, or with more brain involvement. Heparin can only be given by injection. It is used as a first-line immediate treatment for thrombosis, and also if warfarin needs to be stopped (e.g. prior to and during an operation).

In pregnancy, warfarin is contraindicated especially, during the first half of the pregnancy. Daily heparin injections are used when there has been thrombosis or in patients with a number of miscarriages.

The future

Recognition of the syndrome and its successful treatment have had a major impact in medicine. Up to 1 in 5 of all strokes in people under 45 years old, 1 in 5 recurrent miscarriages, and I in 5 DVTs are associated with aPL, not to mention an unknown number of individuals with migraine, multiple sclerosis, memory loss and epilepsy, in whom recognition and treatment of the correct diagnosis could be life altering.