دورية أكاديمية
أعرض في EDS

The intrinsic coagulation pathway plays a dominant role in driving hypercoagulability in ANCA-associated vasculitis.

التفاصيل البيبلوغرافية
العنوان: The intrinsic coagulation pathway plays a dominant role in driving hypercoagulability in ANCA-associated vasculitis.
المؤلفون: Busch MH; Department Nephrology and Clinical Immunology, Maastricht University Medical Center, Maastricht, The Netherlands.; Department Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht, The Netherlands., Ysermans R; Department Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht, The Netherlands., Aendekerk JP; Department Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht, The Netherlands., Timmermans SAMEG; Department Nephrology and Clinical Immunology, Maastricht University Medical Center, Maastricht, The Netherlands.; Department Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht, The Netherlands., Potjewijd J; Department Nephrology and Clinical Immunology, Maastricht University Medical Center, Maastricht, The Netherlands., Damoiseaux JGMC; Department of Central Diagnostic Laboratory, Maastricht University Medical Center, Maastricht, The Netherlands., Spronk HMH; Department Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht, The Netherlands., Ten Cate H; Department Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht, The Netherlands.; Department of Internal Medicine, Thrombosis Expertise Center, Maastricht University Medical Center, Maastricht, The Netherlands., Reutelingsperger CP; Department Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht, The Netherlands., Nagy M; Department Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht, The Netherlands., van Paassen P; Department Nephrology and Clinical Immunology, Maastricht University Medical Center, Maastricht, The Netherlands.; Department Biochemistry, Cardiovascular Research Institute Maastricht, Maastricht, The Netherlands.
المصدر: Blood advances [Blood Adv] 2024 Mar 12; Vol. 8 (5), pp. 1295-1304.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: American Society of Hematology Country of Publication: United States NLM ID: 101698425 Publication Model: Print Cited Medium: Internet ISSN: 2473-9537 (Electronic) Linking ISSN: 24739529 NLM ISO Abbreviation: Blood Adv Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, DC : American Society of Hematology, [2016]-
مواضيع طبية MeSH: Thrombophilia*/etiology , Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis*/complications, Humans ; Antibodies, Antineutrophil Cytoplasmic ; Thrombin ; Blood Coagulation
مستخلص: Abstract: The risk of a venous thrombotic event (VTE) is increased in patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV); however, a detailed understanding of the underlying mechanisms of hypercoagulability is limited. We assessed prospectively different coagulation parameters in 71 patients with active AAV at baseline and after 6 months of follow-up. D-dimers and fibrinogen were increased in most patients at presentation and remained elevated in half of the patients. Particularly, thrombin-antithrombin (T:AT) complex and activated coagulation factors in complex with their natural inhibitors of the intrinsic coagulation pathway (ie, activated FXII:C1 esterase inhibitor [FXIIa:C1Inh], FXIa:AT, and FXIa:alpha1-antitrypsin [FXIa:α1AT]) were profoundly elevated in patients at baseline. Thrombin formation was dominantly correlated with coagulation factors of the intrinsic pathway (ie, FXIIa:AT, FXIa:AT, FXIa:α1AT, and FXIa:C1Inh) compared to the extrinsic pathway (ie, FVIIa:AT). Hypercoagulability correlated with higher disease activity, ANCA levels, C-reactive protein, serum creatinine, and proteinuria. VTEs were observed in 5 out of 71 (7%) patients within 1 month (interquartile range, 1-5) after inclusion. Baseline T:AT levels were significantly higher in patients with VTE than in those without VTE (P = .044), but other clinical or laboratory markers were comparable between both groups. Hypercoagulability is dominantly characterized by activation of the intrinsic coagulation pathway and elevated D-dimers in active AAV. The driving factors of hypercoagulability are yet to be studied but are most likely related to an interplay of increased disease activity, vascular inflammation, and endothelial damage. Future targets for intervention could include inhibitors of the intrinsic coagulation pathway and compounds specifically reducing the hyperinflammatory state.
(© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
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المشرفين على المادة: 0 (Antibodies, Antineutrophil Cytoplasmic)
EC 3.4.21.5 (Thrombin)
تواريخ الأحداث: Date Created: 20240104 Date Completed: 20240305 Latest Revision: 20240309
رمز التحديث: 20240309
مُعرف محوري في PubMed: PMC10918483
DOI: 10.1182/bloodadvances.2023011937
PMID: 38175623
قاعدة البيانات: MEDLINE
الوصف
تدمد:2473-9537
DOI:10.1182/bloodadvances.2023011937