Blood Coagulation

Blood coagulation is essential for stopping bleeding but also drives thromboembolic disorders. Factor XII (FXII)-triggered coagulation promotes thrombosis while being dispensable for hemostasis, making it a potential anticoagulant target. However, its physiological role remains unclear. Here, we demonstrate that FXII-driven coagulation enhances innate immunity by trapping pathogens and restricting bacterial infection in mice. Streptococcus pneumoniae infection was more severe in FXII-deficient (F12-/-) mice, with increased pulmonary bacterial burden, systemic spread, and mortality. Similarly, Staphylococcus aureus skin infections and systemic dissemination were exacerbated in F12-/- mice. Reconstitution with human FXII restored bacterial containment. Plasma kallikrein amplifies FXII activation, and its deficiency aggravated S. aureus skin infections, similarly to F12-/- mice. FXII deficiency impaired fibrin deposition in abscess walls, leading to leaky capsules and bacterial escape. Bacterial long-chain polyphosphate activated FXII, triggering fibrin formation. Deficiency in FXII substrate factor XI or FXII/factor XI co-deficiency similarly exacerbated S. aureus infection. The data reveal a protective role for FXII-driven coagulation in host defense, urging caution in developing therapeutic strategies targeting this pathway.

This retrospective observational study was conducted to investigate the prevalence and clinical implications of drug interactions involving Ginkgo biloba extract on bleeding risk and coagulation profiles. Our analysis utilized data from patients admitted to Hai Phong International Hospital between January 2022 and December 2023. Inclusion criteria consisted of patients aged 18 years and above, those prescribed Ginkgo biloba extract alone or in combination with other medications, and the availability of complete medical records, including medication history, laboratory tests, and clinical outcomes. Out of 2,647 prescriptions meeting the inclusion criteria, 342 exhibited drug interactions with a prevalence rate of 12.94%. Notably, Ginkgo biloba extract frequent interacts with antiplatelets, anticoagulants, and nonsteroidal anti-inflammatory drugs, with Clopidogrel and Aspirin exhibiting the highest prevalence rates of 2.61% each. However, interactions with anticoagulants including direct oral anticoagulants and acenocoumarol, were not statistically significant in our analysis. Omeprazole was a frequently interacting drug (2.34%) of mild severity. Among the 747 patients analyzed for bleeding disorders, 31 (4.15%) exhibited bleeding symptoms. Correlation analysis indicated a strong association between clinical bleeding and abnormal coagulation results (OR, 1.75; p < 0.001). Moreover, significant correlations were found between Ginkgo biloba extract drug interactions and the bleeding risk (OR: 1.08, p < 0.001) and abnormal coagulation (OR: 1.49, p < 0.001). The severity of Ginkgo biloba extract drug interactions did not correlate with bleeding risk (OR: 1.01, p = 0.767) but influenced abnormal coagulation test results (OR: 0.813, p = 0.019). Specific medications, including clopidogrel, aspirin, celecoxib, loxoprofen, nifedipine, and omeprazole, were significantly associated with the risk of bleeding and abnormal coagulation (p < 0.05). Interactions with ticagrelor, etoricoxib, insulin, omeprazole, and domperidone were associated with abnormal coagulation tests without affecting the reported bleeding. These findings underscore the critical need of evaluating potential interactions involving Ginkgo biloba extract drug interactions in clinical pratice, particularly when assessing bleeding risk and managing coagulation.

BackgroundMolecular events that drive endometriosis (EM) and cause accompanying immune deregulation remain elusive. Our purpose was to identify key pathways involved in lesion formation across diverse populations and to detect transcriptomic changes in eutopic endometrium that accompany EM.MethodsWe searched Gene Expression Omnibus and ArrayExpress and performed differential gene expression analysis and a network meta-analysis on nine qualifying datasets. Those contained transcriptomic data on 114 ectopic endometrium samples (EL), 138 eutopic endometrium samples from women with endometriosis (EEM), and 79 eutopic endometrium samples from women without endometriosis (EH). Gene ontology and enrichment analysis were performed in DAVID, Metascape, and Cytoscape, and drug repurposing was done in CMap.ResultsEEM compared to EH upregulated CCL21 and downregulated BIRC3, CEL, and LEFTY1 genes (|log2FC| > 0.5, p C7, logFC = 3.38, p C3, logFC = 2.40, p SERPINE1, logFC = 1.02, p SERPINE2, logFC = 1.54, p CPA3, logFC = 1.54, p KIT, logFC = 0.74, p ConclusionOur results suggest an interplay between complement and coagulation, mast cells, extracellular matrix remodeling, and the JAK/STAT3 pathway in endometriosis. We underscore the significance of complement C3 and propose JAK inhibitors as therapy candidates. Detected expression differences between EEM and EH are important for the development of diagnosis via endometrial biopsy.

BackgroundTrauma-induced coagulopathy with hyperfibrinolysis is associated with high mortality. The protease ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 motifs 13) is cleaved after tissue injury. We analysed the underlying mechanism of ADAMTS13 proteolytic cleavage and the effect of ADAMTS13 on trauma-induced hyperfibrinolysis.MethodsThirty-nine trauma patients with shock were stratified based on ADAMTS13 conformation. Mechanisms of ADAMTS13 cleavage were explored in vitro using blood from healthy volunteers. The role of ADAMTS13 in hyperfibrinolysis was examined using rotational thromboelastometry (ROTEM) and a fibrin formation assay.ResultsADAMTS13 circulated in a truncated and hyperactive form in 23% of trauma patients in shock. Truncated ADAMTS13 was associated with a significant increase in hyperfibrinolysis (ROTEM FIBTEM maximum lysis 85 [62-100] vs 1 [0-7]%, P=0.002) and mortality (44% vs 3%, P=0.007) compared with patients with a closed ADAMTS13 conformation. In vitro, ADAMTS13 was cleaved at its distal self-regulating domains in the presence of tissue plasminogen activator and plasmin, which concentration-dependently increased ADAMTS13 activity. This activation was prevented by tranexamic acid. Hyperactivated ADAMTS13 was associated with hyperfibrinolysis by both ROTEM and fibrin formation assays compared with conditions where ADAMTS13 was inactivated.ConclusionsDuring trauma-induced shock, ADAMTS13 can circulate in a truncated and hyperactivated conformation, which is associated with hyperfibrinolysis and mortality. In vitro, tissue plasminogen activator and plasmin can truncate ADAMTS13, increasing its activity. Additionally, ADAMTS13 directly contributes to hyperfibrinolysis, and tranexamic acid can prevent ADAMTS13 degradation.Institutional ethical review board approval numbersNL58766.018.16, NL74188.018.20.