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

Abstract

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.

Keywords

antiphospholipid syndrome - hypercoagulability - thrombosis - mechanism - human

Authors' Contributions

S.E.D.Ø. conducted the literature search in Ovid (EMBASE) and MEDLINE (PubMed), screened potential articles, performed full-text screening of all the selected studies, interpreted the data, drafted the initial version of the manuscript, and approved the final version. A.V. contributed to the study design, interpreted the data, contributed to writing the manuscript, and approved the final version. R.S.H. contributed to the study design, screened potential articles, participated in full-text screening in cases of disagreement, interpreted the data, contributed to manuscript writing, and approved the final version. M.V.B. conceived the original idea for the study and designed the study, screened potential articles, performed full-text screening of 50% of the selected studies, interpreted the data, supervised manuscript preparation, and approved the final version.

Publication History

Received: 08 April 2025

Accepted: 15 August 2025

Accepted Manuscript online:
18 August 2025

Article published online:
08 September 2025

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