Antiphospholipid syndrome Exploring the etiology in pursuit of targeted treatment strategies

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by arterial or venous thrombosis, obstetric morbidity and microvascular disease in the persistent presence of antiphospholipid antibodies. This thesis aims to provide more insight in the etiology of APS in pursuit of targeted therapeutic strategies. The first part of this thesis focuses on the relationship between the intestinal microbiome and APS. Chapter 3 examines whether a disturbed intestinal microbiota composition contributes to APS pathogenesis and reports on differences in intestinal microbiota composition and the intestinal micro-environment between APS patients and healthy controls. Chapter 4 presents the results of an intervention study that evaluated the effects of the intestinal microbiota modulation through treatment with a poorly absorbed antibiotic on a composite of biochemical APS disease activity markers. The second part of this thesis focuses on thrombotic mechanisms in APS and the efficacy of antithrombotic treatment in obstetric APS. Chapter 5 explores the role of intrinsic pathway activation in APS pathogenesis by evaluating markers of intrinsic pathway activation in APS patients compared to healthy controls. Chapter 6 summarizes the available evidence on the efficacy of low molecular weight heparin to prevent placenta-mediated pregnancy complications in women with APS and previous placenta-mediated pregnancy complications through a systematic review of randomized controlled trials.