Exploring the Mechanisms of Hypercoagulability in Thrombotic Antiphospholipid Syndrome: A Scoping Review of Human...

Thrombosis is the most common manifestation of antiphospholipid syndrome (APS), but concurring evidence of the mechanisms leading to a hypercoagulable state and thereby thrombosis is lacking. Existing reviews on this topic often include both animal and in vitro models. Additionally, studies with a systematic approach and stringent methodology, focusing exclusively on human studies, are lacking. Therefore, we conducted a scoping review of studies with human subjects, focusing on the mechanisms contributing to hypercoagulability in thrombotic APS (T-APS). The process was guided by the PRISMA Extension for Scoping Reviews and performed according to a preregistered protocol in Open Science Framework (https://osf.io/tjdwv). A systematic search of Ovid (EMBASE) and MEDLINE (PubMed) was performed on October 10, 2024. Records investigating mechanisms of hypercoagulability in adults (≥18 years) with T-APS, published between January 2000 and October 2024, were included. A total of 4,160 titles and abstracts were screened, 115 articles were assessed in full text, of which 35 studies fulfilled the predefined eligibility criteria for inclusion. Of the included studies, 8 focused on primary hemostasis, 10 on secondary hemostasis, 9 on fibrinolysis, 4 on neutrophil extracellular traps, 6 on endothelial cells, 3 on complement factors, 5 on monocytes, 3 on oxidized low-density lipoprotein complexes, 2 on oxidative stress, and 1 on amyloid-β1-40. No clear consensus was found regarding the underlying cause of hypercoagulability in T-APS, highlighting the need for further studies with human subjects. Nonetheless, this scoping review indicates that hypercoagulability in T-APS is possibly multifactorial, with no single mechanism being solely responsible.