160 Antiphospholipid Antibody Syndrome

The antiphospholipid antibody syndrome (APS) is a multisystemic autoimmune disease characterized by thromboembolic events, pregnancy morbidity, hematologic, dermatologic, neurologic, and other manifestations in the presence of elevated titers of antiphospholipid antibodies (aPL). Antiphospholipid antibodies are a heterogeneous group of autoantibodies directed against negatively charged phospholipids or phospholipidbinding plasma proteins. The most relevant aPL for identifying patients at risk for immune-mediated thrombosis are anticardiolipin antibodies (aCL), antibodies against b2 glycoprotein I (anti-b2GPI) and lupus anticoagulant (LA). The classification criteria for APS were developed by consensus and designate patients who suffered from vascular thrombosis or pregnancy morbidity associated with the presence of aPL, detected on two or more occasions at least 12 weeks apart (>Table 160.1). These criteria were developed for classification of adult patients with APS and include pregnancy morbidity as a clinical criterion, which is not applicable for the pediatric population. A classification of ‘‘probable APS’’ has been given to patients with aPL that have non-criteria clinical features associated with APS such as livedo reticularis, thrombocytopenia, nephropathy, and neurologic manifestations. Catastrophic antiphospholipid antibody syndrome (CAPS) is a rare, life-threatening variant of APS, characterized by acute microvascular occlusive disease involving at least three organ systems in less than a week. Etiology The cause of APS remains unknown. It may occur as an isolated clinical entity (primary APS) or in association with autoimmune diseases, infections and malignancies. Primary, isolated APS accounts for approximately half of all pediatric patients with APS. The majority of cases associated with underlying autoimmune disease occur in patients with systemic lupus erythematosus (SLE) and lupus-like disease. Preceding or concomitant infections were found in approximately 10% of children with primary APS or APS associated with autoimmune disease. APS associated with malignancies is exceedingly rare in childhood and accounts for less than 1% of all pediatric APS cases. Epidemiology APS is considered the most common acquired hypercoagulation state of autoimmune etiology, and aPL were reported in up to 25% of unselected children with thrombosis. The average age of onset in 121 pediatric APS patients included in an international registry was 10.7 years with the female-to-male ratio 1.2:1. Children of all ethnic background have been affected with APS. Antiphospholipid antibodies can be found in a high percentage of children that do not experience thrombosis. SLE is the autoimmune disease in which aPL occurs in highest percentage, with the reported mean frequencies of 44% for aCL, 40% for anti-b2GPI, and 22% for LA, respectively. The estimated incidence of thromboembolic events in pediatric SLE patients with positive LAwas 54% and with positive aCL 22%. Lowlevels of aPL can be found in childrenwithout any underlying disorder. These naturally occurring aPL are usually transient and could be the result of previous infections or vaccinations that are common in the pediatric population. LA can be rarely found in apparently healthy children as an incidental finding of prolonged activated partial thromboplastin time (aPTT) in pre-operative coagulation screening. The risk of future thrombosis is exceedingly low in otherwise healthy children who were incidentally found to have positive aPL.