7B.2 Antiphospholipid syndrome: clinical manifestations and treatment

Abstract

Clinical manifestations Antiphospholipid syndrome has a heterogeneous clinical presentation and, consequently, may be encountered by clinicians in a range of specialties. Thrombosis of the deep limb veins, sometimes with pulmonary embolism, is a common first manifestation. However any region of the venous system can be involved including superficial, mesenteric, portal, intracranial and retinal veins. The characteristic serological feature of the syndrome is the presence of antiphospholipid antibody, typically lupus inhibitor and/or anticardiolipin/anti-b2-glycoprotein I antibody. Depending on the composition of the population examined around 3% of patients with a first DVT are positive for lupus inhibitor. Arterial thrombosis occurs also. Ischaemic stroke is the commonest manifestation, but myocardial infarction, peripheral gangrene and thrombotic occlusion of any part of the arterial tree, including mesenteric, adrenal and renal vessels, can occur. Occasionally, clinical manifestations can be ascribed to involvement of the microvasculature, for example renal impairment and seizures. “Catastrophic antiphospholipid syndrome” is an acute, dramatic and life-threatening form of thrombotic microangiopathy affecting multiple organs. Kidneys, lungs, skin and central nervous system are frequently involved. Fortunately this presentation is encountered exceedingly uncommonly. Other reported manifestations of antiphospholipid syndrome include skin lesions (typically livedo reticularis but also ulceration), cardiac valve lesions (ranging from valve thickening to sterile endocarditis with vegetations), non-stroke neurological manifestations (such as sensori/neural deafness, chorea, cognitive impairment and multifocal ischaemia mimicking demyelinating disease) and consumptive haematological cytopenias (autoimmune haemolytic anaemia and thrombocytopenia). Pregnancy failure and maternal morbidity are well recognized manifestations of antiphospholipid syndrome. Recurrent miscarriage, fetal growth retardation, fetal death and severe (often early) pre/eclampsia may occur. In many women these are the only manifestations, health remaining good when non-pregnant. Placental thrombosis may explain some of these events but alternative mechanisms probably account for very early pregnancy failure. In some cases antiphospholipid syndrome complicates established connective tissue disease, classically systemic lupus erythematosus, but in many others thrombosis or pregnancy failure is the only feature. The diagnosis of antiphospholipid syndrome may be problematic because of the high background prevalence of arterial and venous thrombosis in adults, as well as the common phenomenon of transient antiphospholipid antibodies which are often associated with self-limiting infections and are not usually associated with thrombotic events. Furthermore antiphospholipid antibodies occur in some chronic infections (classically syphilis but also chronic viral infections including hepatitis C and HIV) and iatrogenically, for example due to phenothiazine treatment. Again, thrombosis is not usually a feature in these circumstances. Diagnostic uncertainty is exacerbated by the poor performance and unreliability of the laboratory tests for antiphospholipid antibodies. Furthermore, low titre anticardiolipin antibodies are a frequent finding in the general population and are of uncertain significance.