Graham Hughes1 and Shirish Sangle2
(1)
The London Lupus Centre, London Bridge Hospital, London, UK
(2)
Louise Coote Lupus Unit, St Thomas’ Hospital, London, UK
Abstract
The major clinical features are thrombosis – both in veins and in arteries, (the latter distinguishing Hughes Syndrome from most other prothrombotic disorders) – and recurrent pregnancy loss. The myriad of clinical features follow on from this tendency to “sticky blood!”.
The major clinical features are thrombosis – both in veins and in arteries, (the latter distinguishing Hughes Syndrome from most other prothrombotic disorders) – and recurrent pregnancy loss. The myriad of clinical features follow on from this tendency to “sticky blood!”.
2.1 Pathogenesis
The disease is considered one of the auto-immune diseases, sometimes associated with other conditions such as lupus, but more often standing in isolation. Antiphospholipid antibodies (aPL) are very strongly linked to the clinical features of the disease. The mechanisms by which they cause the blood to clot are still unclear, though effects on platelets, on clotting factors and on endothelial cells have all been suggested.
Other mysteries remain: for example, what triggers a thrombosis in aPL positive individuals? And why, for example, if a “neurological” feature such as headaches or memory loss is due to blood clots and infarction, do the symptoms often resolve with anticoagulant treatment? Perhaps blood “sludging” is responsible in some cases of thrombosis. And do other influences play a role – genetics, smoking, diet, infection etc.? In many cases the answer is a clear “yes”.
2.2 Vein Clots
A deep vein thrombosis (DVT), for example in the leg or the arm, is often the first manifestation. Studies from a number of major hospitals have suggested that positive aPL tests are seen in up to 20% of all DVTs coming into casualty departments.
Often the thromboses are major, and pulmonary emboli – sometimes fatal, are not uncommon. Recurrent pulmonary embolism may lead to some of the cases of pulmonary hypertension seen in a small number of patients with Hughes Syndrome.
Internal venous thrombosis can affect almost any organ, e.g., the eye, (retinal vein thrombosis), liver (e.g., Budd Chiari), kidney (nephrotic syndrome), adrenal (Addison’s disease), and the brain (e.g., sagittal sinus thrombosis) (Fig. 2.1).
Figure 2.1
A CT angiograph of a brain showing sagittal sinus thrombosis in a patient with Hughes Syndrome
2.3 Artery Thrombosis
Cases can present dramatically, for example, with acute femoral artery occlusion leading to ischaemia and amputation. Vessels as big as the aorta can thrombose.
As with venous thrombosis, artery clots can lead to damage and failure in major organs such as the brain (stroke) and heart (myocardial infarction).
2.4 Pregnancy Loss
Failure of delivery of blood supply to the developing fetus can result in miscarriage. Hughes Syndrome is now recognised as the commonest, treatable cause of recurrent pregnancy loss. Tragically, some women suffer 8, 10, 12 and even more miscarriages before the diagnosis is made – a situation that could so easily have been prevented with simple aspirin or heparin.
On a positive note, research on the pregnancy aspects of Hughes Syndrome has contributed much to our knowledge of the disease – see Chap. 3.
2.5 The Brain
Of all the organs in the body, the brain seems particularly vulnerable in Hughes Syndrome. The clinical features of cerebral APS cover the whole of neurology, ranging from migraines, to stroke, to myelitis, to memory loss.
Indeed the syndrome is not only becoming a recognised important cause of stroke (e.g., 1 in 5 of all strokes in younger (under 45) individuals), but may come to be regarded as perhaps the major link between migraine and stroke.
2.6 Other Organs
Cardiac ischaemia is becoming recognised as an important feature in some cases of Hughes Syndrome (see Chap. 9).
As the story of the syndrome has unfolded, Hughes Syndrome has embraced all branches of medicine and surgery, including orthopaedics (ischaemic bone fracture), ENT (balance problems), dermatology (recurrent skin ulcers, livedo), psychiatry (memory loss) and transplant surgery (more complications in aPL-positive transplant patients).
Finally, somewhat bizarrely, low platelet counts can be seen, sometimes acute and severe, but more commonly in the 100,000 range (see Chap. 18).