Is Obstetric Antiphospholipid Syndrome a Primary Nonthrombotic, Proinflammatory, Complement-Mediated Disorder Related to Antiphospholipid Antibodies?

Abstract

Pregnancy loss is the main obstetrical complication of the obstetric antiphospholipid syndrome. Classically, such losses have been attributed to placental thrombosis and infarcts, although in many cases there is no evidence of decidual thrombosis or placental vasculopathy, and instead inflammatory signs are present. In addition, the prevalence of systemic thrombosis is low in obstetric antiphospholipid syndrome, suggesting an alternative pathogenesis. There is evidence that antiphospholipid antibodies, mainly beta2-glycoprotein-I/anti-beta2-glycoproteina-I complexes, activate both classical and alternative complement pathways. Complement proteins may injure trophoblast cells, recruiting and activating monocytes and neutrophils. Free radicals and proteolytic enzymes could also attack trophoblastic cells, and amplification of the causal loop between tissue factor, inflammatory cells, and complement proteins could also be a factor. Overall, these diverse mechanisms may explain both inflammatory and thrombotic placental alterations. The role played by certain pro-inflammatory cytokines, mainly tumor necrosis factor-alpha, and the altered balance between angiogenic and anti-angiogenic factors remains to be clarified. In the end, obstetric antiphospholipid syndrome seems to be a clinical subset of classical APS. In these women, systemic thrombotic risk seems to be low. Current knowledge about inflammatory pathway involvement in obstetric antiphospholipid syndrome will permit us to modify the time to start heparin treatment, currently recommended to begin it as soon as possible after pregnancy confirmation. Obstetricians & Gynecologists, Family Physicians. After completion of this article, the reader will be able to recall manifestations of obstetric antiphospholipid syndrome, describe nonthrombotic mechanisms that may affect obstetric outcomes in women with antiphospholipid syndrome, and predict changes in the evaluation and treatment of obstetric patients with antiphospholipid syndrome should inflammatory factors prove to be an important feature of antiphospholipid syndrome.