Diagnosis and management of the antiphospholipid syndrome

Abstract

Antiphospholipid syndrome (APS) is characterized by thrombosis and/or pregnancy complications in the presence of persistent antiphospholipid antibodies (APLA). Laboratory diagnosis of APLA depends upon the detection of a lupus anticoagulant, which prolongs phospholipid-dependent anticoagulation tests, and/or anticardiolipin (aCL) and anti-β2-glycoprotein-1 (β2GPI) antibodies. APLA are primarily directed towards phospholipid binding proteins. Pathophysiologic mechanisms underlying thrombosis and pregnancy loss in APS include APLA induced cellular activation, inhibition of natural anticoagulant and fibrinolytic systems, and complement activation, among others. There is a high rate of recurrent thrombosis in APS, especially in triple positive patients (patients with lupus anticoagulants, aCL and anti-β2GPI antibodies), and indefinite anticoagulation with a vitamin K antagonist is the standard of care for thrombotic APS. There is currently insufficient evidence to recommend the routine use of direct oral anticoagulants (DOAC) in thrombotic APS. Aspirin with low molecular weight or unfractionated heparin may reduce the incidence of pregnancy loss in obstetric APS. Recent insights into the pathogenesis of APS have led to the identification of new potential therapeutic interventions, including anti-inflammatory and immunomodulatory therapies. Additional research is needed to better understand the effects of APLA on activation of signaling pathways in vascular cells, to identify more predictive biomarkers that define patients at greatest risk for a first or recurrent APLA-related clinical event, and to determine the safety and efficacy of DOACs and novel anti-inflammatory and immune-modulatory therapies for refractory APS.

Circulating plasmablasts contribute to antiphospholipid antibody production, associated with type I interferon upregulation

“…The pathophysiology of APS is incompletely understood. Most of the related studies have so far focused on aPL‐cell interaction, intracellular signaling, and subsequent expression of procoagulant genes such as tissue factor . Given the pathogenicity of aPL, which is also supported by the fact that a subject with a high titer and/or a variety of aPL has an increased risk of thrombosis , it would be of value to elucidate how and by which cells aPL are produced.…”

Expert consensus on the diagnosis and treatment of thrombocytopenia in adult critical care patients in China

“…A small number of patients may have multiple incidents of thrombosis within a week and subsequently develop acatastrophic vascular occlusion called catastrophic antiphospholipid syndrome (CAPS). APS is confirmed with routine tests that show thrombocytopenia, neutropenia, hemolytic anemia, and positive serum antiphospholipid antibodies (aCL, LAC, β 2 GPI antibodies) [55].…”

Tromboembolismo pulmonar recurrente en un paciente con síndrome antifosfolipídico y trombocitopenia inducida por heparina

“…El SAF es una enfermedad sistémica adquirida que requiere para su diagnóstico la coexistencia de criterios clínicos, basados en fenómenos trombóticos, arteriales o de comorbilidades obstétricas, asociados criterios bioquímicos con positividad para uno o más anticuerpos antifosfolipídicos de forma sostenida en el tiempo 10 . Dada la elevada frecuencia de fenómenos trombóticos e incluso recurrencia de los mismos, el estándar de tratamiento consiste en su anticoagulación con AVK, siendo escasa la evidencia para la utilización de los DOACs 11 .…”