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Objectives Since Antiphospholipid syndrome (APS) identification in 1983, research on APS has progressed, but no targeted therapies other than anticoagulation are yet available, with a mortality rate of 9.3% at 10 years.The aim of the current systematic literature reviews (SLRs) is to identify and compare upregulated proteins in thrombotic APS (tAPS) and non-aPL-thrombosis, providing useful insights into APS pathogenesis.Methods We conducted two SLRs in accordance with PRISMA guidelines to identify proteins upregulated in tAPS and non-aPL-related thrombosis. Eligible studies were controlled observational and focused on proteomics. Gene Ontology (GO) enrichment and network analyses were performed on identified proteins.Results Of 108 and 209 records identified, 7 and 13 were included in the SLR for tAPS and non-aPL thrombosis, respectively. The review identified 118 upregulated proteins in tAPS and 319 in non-aPL-related thrombosis. GO analysis revealed distinct biological process enrichment.The top 3 enriched biological process terms among the upregulated proteins in tAPS were platelet aggregation (strength 1.69, FDR 1.08×10^-14), platelet activation (strength 1.39, FDR 4.44×10^-14), and blood coagulation (strength 1.24, FDR 1.08×10^-14). This corresponds to enrichment levels of approximately 49-fold for platelet aggregation, 25-fold for platelet activation, and 17-fold for blood coagulation compared to expectation. In contrast, in non-aPL-related thrombosis, the upregulated proteins were most strongly associated with hemostasis (strength 1.18, FDR 1.76×10^-31), blood coagulation (strength 1.19, FDR 6.01×10^-31), and wound healing (strength 1.35, FDR 4.61×10^-18) (figure 1).The molecular functions of upregulated proteins in tAPS involve receptor or protein complex binding, while in non-aPL-related thrombosis, they focus on enzymatic activity.The top 10 terms and their associated proteins in tAPS and non-aPL-related thrombosis (table 1), revealing distinct functional patterns: upregulated proteins in tAPS are notably enriched for MAC components, suggesting enhanced complement-mediated activity, whereas proteins upregulated in non-aPL-related thrombosis are enriched for serpins, indicating a predominance of protease inhibition and regulatory processes.Abstract PO:01:019 Table 1Top 10 terms and related proteins in tAPS and non-aPl related thrombosisAbstract PO:01:019 Figure 1Gene Ontology Enrichment Analysis of proteins upregulated in thrombotic APS (A) and non-aPL-thrombosis (B)Conclusions Our findings highlight the central role of platelet-related processes in tAPS pathogenesis, distinguishing it from non-aPL thrombosis. By elucidating the unique proteomic and functional characteristics of tAPS, this study provides a foundation for future research into targeted therapies that address platelet involvement in APS pathogenesis.