24 - Antiphospholipid Syndrome

Abstract

The antiphospholipid syndrome (APS) is an autoimmune multisystem disease mediated by antiphospholipid antibodies (APLA) that primarily manifests as intravascular thrombosis. APS may occur as an isolated clinical entity (primary APS) or in association with other autoimmune diseases, infections, and malignancies (secondary APS). Multiple pathogenic mechanisms have been proposed by which APLA may predispose to thrombosis including interaction with cellular components, activation of the coagulation cascade, impairment of the fibrinolytic system, inhibition of natural anticoagulants, and complement activation. Children with APLA may present with any combination of vascular occlusive events or with a variety of nonthrombotic manifestations such as thrombocytopenia, autoimmune hemolytic anemia, livedo reticularis, and various neurologic manifestations. Venous thrombosis is the most common vascular occlusive manifestation occurring in up to 60% of affected children, followed by arterial thrombosis in approximately 30% and small-vessel thrombosis in less than 10% of pediatric APS patients. Rarely, patients develop catastrophic antiphospholipid syndrome (CAPS), a life- and organ-threatening condition in which microthrombi throughout the circulation cause multiorgan system dysfunction in the setting of systemic inflammatory activation and APLA. Management strategies for children with APS are based on a few pediatric observational cohort studies and modified recommendations for adults with APS. The treatment includes initial stabilization with dissolution of the thrombus, followed by prevention of subsequent thrombosis. Patients with high-risk APLA profiles including multiple APLA positivity, presence of lupus anticoagulants, or persistently high APLA titers have a high risk for recurrent thrombosis and should receive long-term anticoagulation.