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Molecular mechanisms underlying thrombosis in systemic lupus erythematosus – A Systematic review

Larsen, Mads L. ; Nørgaard, Laura ; Linge, Petrus LU orcid ; Larsen, Julie B. ; Langkilde, Henrik Z. ; Hauge, Ellen M. ; Thiel, Steffen ; Voss, Anne ; Bengtsson, Anders LU and Troldborg, Anne (2025) In Seminars in Arthritis and Rheumatism 72.
Abstract

Patients with systemic lupus erythematosus (SLE) face an approximately 30 % risk of thrombosis post-diagnosis. However, there remains significant knowledge gaps regarding causative mechanisms, and there is a lack of specific antithrombotic guidelines. This systematic review aims to examine the existing literature regarding the mechanisms contributing to thrombosis risk in SLE, focusing on five predefined procoagulant domains: autoantibodies (including antiphospholipid antibodies (aPL)), the complement system, platelets, the endothelium, and the coagulation system. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statements and searched in PubMed and Embase without time restrictions.... (More)

Patients with systemic lupus erythematosus (SLE) face an approximately 30 % risk of thrombosis post-diagnosis. However, there remains significant knowledge gaps regarding causative mechanisms, and there is a lack of specific antithrombotic guidelines. This systematic review aims to examine the existing literature regarding the mechanisms contributing to thrombosis risk in SLE, focusing on five predefined procoagulant domains: autoantibodies (including antiphospholipid antibodies (aPL)), the complement system, platelets, the endothelium, and the coagulation system. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statements and searched in PubMed and Embase without time restrictions. Risk of bias assessment was performed using a pre-specified evaluation tool. Out of 3,747 initially identified publications, 30 studies were included, with 28 demonstrating robust methodological quality in the risk of bias assessment. The studies were experimental, involving blood samples from cross-sectional SLE cohorts, except one animal -and one case-control study. We identified six different thrombosis mechanisms of action. Most studies concentrated on autoantibodies, predominantly aPL. Shared mechanisms between aPL and other autoantibodies may account for the increased thrombosis risk in aPL-negative SLE patients. Significant knowledge gaps remain, particularly regarding the role of the complement system in SLE-related thrombosis. Also, most research relies on cross-sectional designs, emphasizing the need for prospective cohort studies to better assess clinical factors. Finally, comprehensive studies examining the interactions between multiple procoagulant factors and their link to thrombosis are lacking. Closing these gaps in future research could improve both preventive and personalized treatment strategies for thrombosis in SLE.

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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Antiphospholipid antibodies, Embolism and thrombosis, Mechanism of action, Systematic review, Systemic lupus erythematosus
in
Seminars in Arthritis and Rheumatism
volume
72
article number
152707
publisher
W.B. Saunders
external identifiers
  • scopus:86000487177
  • pmid:40086157
ISSN
0049-0172
DOI
10.1016/j.semarthrit.2025.152707
language
English
LU publication?
yes
id
a694fdf5-f028-4a6b-acb3-ff8b12d906dd
date added to LUP
2025-06-09 09:45:13
date last changed
2025-07-07 12:39:11
@article{a694fdf5-f028-4a6b-acb3-ff8b12d906dd,
  abstract     = {{<p>Patients with systemic lupus erythematosus (SLE) face an approximately 30 % risk of thrombosis post-diagnosis. However, there remains significant knowledge gaps regarding causative mechanisms, and there is a lack of specific antithrombotic guidelines. This systematic review aims to examine the existing literature regarding the mechanisms contributing to thrombosis risk in SLE, focusing on five predefined procoagulant domains: autoantibodies (including antiphospholipid antibodies (aPL)), the complement system, platelets, the endothelium, and the coagulation system. The review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statements and searched in PubMed and Embase without time restrictions. Risk of bias assessment was performed using a pre-specified evaluation tool. Out of 3,747 initially identified publications, 30 studies were included, with 28 demonstrating robust methodological quality in the risk of bias assessment. The studies were experimental, involving blood samples from cross-sectional SLE cohorts, except one animal -and one case-control study. We identified six different thrombosis mechanisms of action. Most studies concentrated on autoantibodies, predominantly aPL. Shared mechanisms between aPL and other autoantibodies may account for the increased thrombosis risk in aPL-negative SLE patients. Significant knowledge gaps remain, particularly regarding the role of the complement system in SLE-related thrombosis. Also, most research relies on cross-sectional designs, emphasizing the need for prospective cohort studies to better assess clinical factors. Finally, comprehensive studies examining the interactions between multiple procoagulant factors and their link to thrombosis are lacking. Closing these gaps in future research could improve both preventive and personalized treatment strategies for thrombosis in SLE.</p>}},
  author       = {{Larsen, Mads L. and Nørgaard, Laura and Linge, Petrus and Larsen, Julie B. and Langkilde, Henrik Z. and Hauge, Ellen M. and Thiel, Steffen and Voss, Anne and Bengtsson, Anders and Troldborg, Anne}},
  issn         = {{0049-0172}},
  keywords     = {{Antiphospholipid antibodies; Embolism and thrombosis; Mechanism of action; Systematic review; Systemic lupus erythematosus}},
  language     = {{eng}},
  publisher    = {{W.B. Saunders}},
  series       = {{Seminars in Arthritis and Rheumatism}},
  title        = {{Molecular mechanisms underlying thrombosis in systemic lupus erythematosus – A Systematic review}},
  url          = {{http://dx.doi.org/10.1016/j.semarthrit.2025.152707}},
  doi          = {{10.1016/j.semarthrit.2025.152707}},
  volume       = {{72}},
  year         = {{2025}},
}