Managing Antiphospholipid Syndrome in Children and Adolescents: Current and Future Prospects

Abstract

Pediatric antiphospholipid syndrome (APS) is a rare acquired multisystem autoimmune thromboinflammatory condition characterized by thrombotic and non-thrombotic clinical manifestations. APS in children and adolescents typically presents with large-vessel thrombosis, thrombotic microangiopathy, and, rarely, obstetric morbidity. Non-thrombotic clinical manifestations are frequently seen in pediatric APS and may be present even before the vascular thrombotic events occur. We review insights into the pathogenesis of APS and discuss potential targets for therapy. The identification of multiple immunologic abnormalities in patients with APS reveals molecular targets for current or future treatment. Management strategies, especially for APS in adolescents, require screening for additional prothrombotic risk factors and consideration of counseling regarding contraceptive strategies, lifestyle recommendations, treatment adherence, and mental health issues associated with this autoimmune thrombophilia. The main goal of therapy in pediatric APS is the prevention of thrombosis. The management of acute thrombosis events in children and adolescents is the same as for primary APS, which involves isolated occurrences, and secondary APS, which is seen in association with another autoimmune disease, e.g., systemic lupus erythematosus. A pediatric hematologist should be consulted so other differential thrombophilic conditions can be eliminated. Therapy includes unfractionated heparin or low-molecular-weight heparin followed by vitamin K antagonists. Treatment of catastrophic APS involves triple therapy (anticoagulation, intravenous corticosteroid pulse therapy, and plasma exchange) and may include intravenous immunoglobulin for children and adolescents with this condition. New drugs such as eculizumab and sirolimus seem to be promising drugs for APS.

Provoked deep vein thrombosis and saddle pulmonary embolism in a pediatric patient with multiple genetic risk factors for venous thromboembolism

“…1 Repeat testing at 3 months re-demonstrated the same findings for his antiphospholipid antibody profile, which was consistent with a diagnosis of APS based on the Sapporo criteria. 2 Repeat Doppler ultrasonography at 3 months demonstrated improvement but residual nonocclusive thrombosis of left femoral and popliteal veins. This 17-year-old Caucasian male's challenging presentation of DVT and saddle PE occurred in the setting of trauma, immobilization, obesity, and double-heterozygosity for FVL/PT-G20210A with con-current APS.…”

“…7 For APS alone, there is conflicting evidence for the use of low-dose aspirin for primary prevention of arterial and venous thromboembolism. 2,8 Regarding secondary prevention of venous thromboembolism in patients with APS, as would apply to our patient, warfarin monotherapy is routinely utilized with a target international normalized ratio of 2.0-3.0. In the event of recurrent venous thrombosis in a patient with APS while on warfarin, the European Alliance of Associations for Rheumatology recommends consideration of warfarin combined with low-dose aspirin or extended therapeutic enoxaparin.…”

“…In the event of recurrent venous thrombosis in a patient with APS while on warfarin, the European Alliance of Associations for Rheumatology recommends consideration of warfarin combined with low-dose aspirin or extended therapeutic enoxaparin. 2,8 After extensive discussion with the family, the patient plans to Much of the literature examining risk of VTE with genetic mutations specifically exclude individuals with inciting factors, such as trauma, which was an important provoking factor for this patient. This case also highlights the importance of evaluation for thrombophilia in patients in select circumstances with extensive thrombus burden, even in the setting of known risk factors such as trauma and obesity, as the results may have lifelong clinical implications.…”