دورية أكاديمية
The intrinsic coagulation pathway plays a dominant role in driving hypercoagulability in ANCA-associated vasculitis.
العنوان: | The intrinsic coagulation pathway plays a dominant role in driving hypercoagulability in ANCA-associated vasculitis. |
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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.) |
References: | Eur Heart J. 2006 Dec;27(24):2975-81. (PMID: 17132648) Nephrol Dial Transplant. 2015 Apr;30 Suppl 1:i53-9. (PMID: 25523447) Haematologica. 2023 May 01;108(5):1417-1422. (PMID: 36519327) Ann Rheum Dis. 2009 Apr;68(4):564-7. (PMID: 19015208) Kidney Int. 2018 Jul;94(1):139-149. (PMID: 29606398) Ann Rheum Dis. 2009 Dec;68(12):1827-32. (PMID: 19054820) Semin Thromb Hemost. 2010 Feb;36(1):34-40. (PMID: 20391294) JCI Insight. 2018 Feb 8;3(3):. (PMID: 29415887) Circulation. 2020 Nov 3;142(18):1787-1790. (PMID: 32946302) Nat Med. 2009 Jun;15(6):623-5. (PMID: 19448636) Arterioscler Thromb Vasc Biol. 2020 Jan;40(1):103-111. (PMID: 31766871) Nat Med. 2010 Aug;16(8):887-96. (PMID: 20676107) Arthritis Rheumatol. 2015 Oct;67(10):2780-90. (PMID: 26097236) Kidney Int. 2022 Nov;102(5):1115-1126. (PMID: 35998848) J Immunol. 2007 Feb 1;178(3):1845-51. (PMID: 17237435) Front Immunol. 2012 Nov 12;3:333. (PMID: 23162551) J Am Soc Nephrol. 2008 Dec;19(12):2421-9. (PMID: 18701607) J Rheumatol. 2013 Dec;40(12):2042-6. (PMID: 24128780) Arterioscler Thromb Vasc Biol. 2014 Sep;34(9):1977-84. (PMID: 25012129) Kidney Int. 2023 Jul;104(1):151-162. (PMID: 37088424) Thromb Res. 2022 Jan;209:106-114. (PMID: 34922160) Rheumatology (Oxford). 2021 Oct 2;60(10):4616-4623. (PMID: 33506869) Ann Rheum Dis. 2014 Oct;73(10):1854-63. (PMID: 23873874) Ann Rheum Dis. 2016 Sep;75(9):1583-94. (PMID: 27338776) Rheumatology (Oxford). 2021 Oct 2;60(10):4654-4661. (PMID: 33523099) BMC Nephrol. 2021 Aug 26;22(1):290. (PMID: 34445984) Clin Rheumatol. 2021 Jul;40(7):2843-2853. (PMID: 33452661) Arthritis Rheum. 2013 Jan;65(1):1-11. (PMID: 23045170) |
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 |
تدمد: | 2473-9537 |
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DOI: | 10.1182/bloodadvances.2023011937 |