The Antiphospholipid Syndrome

Abstract

The antiphospholipid syndrome (APS) is a multi-system autoimmune disorder characterized by recurrent arterial and venous thromboses and pregnancy morbidity (Hughes 1983). The most common clinical manifestations of the APS are shown in Table 16.1. Cutaneous manifestations of the APS include livedo reticularis (livedo racemosa), leg ulcers, skin necrosis, superficial thrombophlebitis, splinter hemorrhages, digital ischemia, and gangrene. Many of these features must be distinguished from vasculitis, which can also be associated with these findings. The APS is linked to multiple central nervous system manifestations. These are listed in Table 16.2. The APS can occur in a primary form which is not associated with another underlying condition. In addition, it can develop concurrently with disorders such as systemic lupus erythematosus (SLE). Antiphospholipid antibodies (aPL) are a heterogeneous group of immunoglobulins directed at phospholipid binding proteins. Three antibodies are central to the diagnosis of APS: the lupus anticoagulant (LA), anti-cardiolipin antibodies (aCL), and β-2-glycoprotein 1. aCL and β-2-glycoprotein 1 are detected by enzyme-linked immunosorbent assays. The LA is commonly detected by the dilute Russell viper venom time, but other assays are also available (Brandt et al. 1995). aPL are found in less than 1% of healthy populations of all ages. However, the figure is substantially higher among healthy older populations — as high as 5%. The prevalence in SLE is substantially higher, on the order of 24% for IgG aCL, 13% for IgM aCL, and 15% for LA (Cervera et al. 1993). APS has a significant impact on morbidity and mortality (Shah et al. 1998; Jouhikainen et al. 1993; Schulman et al. 1998; Ruiz-Irastorza et al. 2004). In one longitudinal study of SLE patients, aPL-related thromboses accounted for 27% of all deaths in the cohort (Cervera et al. 1993). The term “catastrophic APS” refers to a rare but potentially lethal disorder characterized by accelerated thrombosis, multiple organ involvement that includes renal thrombotic microangiopathy and death in a high percentage of patients (Bucciarelli et al. 2006). The combination of anticoagulation, glucocorticoids, and plasma exchange is a useful treatment approach to the catastrophic APS (Bucciarelli et al. 2006). Immuno-suppression, particularly with cyclophosphamide, should be avoided. Arterial and venous events associated with the APS are treated initially with unfractionated or low molecular weight heparins, followed by oral anticoagulation with warfarin. Women with APS are at high risk of complications during pregnancy and in the postpartum period. In the postnatal period, women with Thrombotic APS should be given thromboprophylaxis with subcutaneous hepa-rin followed by the resumption of oral anticoagulation as soon as possible. Controversies in the management of patients during pregnancy are discussed.