Contact and intrinsic coagulation pathways are activated and associated with adverse clinical outcomes in COVID-19.

Autor:	Henderson MW; University of North Carolina (UNC) Blood Research Center, UNC at Chapel Hill, Chapel Hill, NC., Lima F; Department of Internal Medicine, School of Medical Sciences, University of Campinas, Campinas, Brazil., Moraes CRP; Department of Internal Medicine, School of Medical Sciences, University of Campinas, Campinas, Brazil., Ilich A; University of North Carolina (UNC) Blood Research Center, UNC at Chapel Hill, Chapel Hill, NC.; Division of Hematology, Department of Medicine, UNC at Chapel Hill, Chapel Hill, NC., Huber SC; Hematology and Hemotherapy Center, and., Barbosa MS; Department of Internal Medicine, School of Medical Sciences, University of Campinas, Campinas, Brazil., Santos I; Hematology and Hemotherapy Center, and., Palma AC; Department of Internal Medicine, School of Medical Sciences, University of Campinas, Campinas, Brazil., Nunes TA; Department of Internal Medicine, School of Medical Sciences, University of Campinas, Campinas, Brazil., Ulaf RG; Department of Internal Medicine, School of Medical Sciences, University of Campinas, Campinas, Brazil., Ribeiro LC; Department of Internal Medicine, School of Medical Sciences, University of Campinas, Campinas, Brazil., Bernardes AF; Department of Internal Medicine, School of Medical Sciences, University of Campinas, Campinas, Brazil., Bombassaro B; Obesity and Comorbidities Research Center, University of Campinas, Campinas, Brazil., Dertkigil SSJ; Department of Internal Medicine, School of Medical Sciences, University of Campinas, Campinas, Brazil., Moretti ML; Department of Internal Medicine, School of Medical Sciences, University of Campinas, Campinas, Brazil., Strickland S; Patricia and John Rosenwald Laboratory of Neurobiology and Genetics, The Rockefeller University, New York, NY; and., Annichino-Bizzacchi JM; Department of Internal Medicine, School of Medical Sciences, University of Campinas, Campinas, Brazil.; Hematology and Hemotherapy Center, and., Orsi FA; Department of Internal Medicine, School of Medical Sciences, University of Campinas, Campinas, Brazil., Mansour E; Department of Internal Medicine, School of Medical Sciences, University of Campinas, Campinas, Brazil., Velloso LA; Department of Internal Medicine, School of Medical Sciences, University of Campinas, Campinas, Brazil.; Obesity and Comorbidities Research Center, University of Campinas, Campinas, Brazil., Key NS; University of North Carolina (UNC) Blood Research Center, UNC at Chapel Hill, Chapel Hill, NC.; Division of Hematology, Department of Medicine, UNC at Chapel Hill, Chapel Hill, NC.; Department of Pathology and Laboratory Medicine, UNC at Chapel Hill, Chapel Hill, NC., De Paula EV; Department of Internal Medicine, School of Medical Sciences, University of Campinas, Campinas, Brazil.; Hematology and Hemotherapy Center, and.
Jazyk:	angličtina
Zdroj:	Blood advances [Blood Adv] 2022 Jun 14; Vol. 6 (11), pp. 3367-3377.
DOI:	10.1182/bloodadvances.2021006620
Abstrakt:	Coagulation activation is a prominent feature of severe acute respiratory syndrome coronavirus 2 (COVID-19) infection. Activation of the contact system and intrinsic pathway has increasingly been implicated in the prothrombotic state observed in both sterile and infectious inflammatory conditions. We therefore sought to assess activation of the contact system and intrinsic pathway in individuals with COVID-19 infection. Baseline plasma levels of protease:serpin complexes indicative of activation of the contact and intrinsic pathways were measured in samples from inpatients with COVID-19 and healthy individuals. Cleaved kininogen, a surrogate for bradykinin release, was measured by enzyme-linked immunosorbent assay, and extrinsic pathway activation was assessed by microvesicle tissue factor-mediated factor Xa (FXa; MVTF) generation. Samples were collected within 24 hours of COVID-19 diagnosis. Thirty patients with COVID-19 and 30 age- and sex-matched controls were enrolled. Contact system and intrinsic pathway activation in COVID-19 was demonstrated by increased plasma levels of FXIIa:C1 esterase inhibitor (C1), kallikrein:C1, FXIa:C1, FXIa:α1-antitrypsin, and FIXa:antithrombin (AT). MVTF levels were also increased in patients with COVID-19. Because FIXa:AT levels were associated with both contact/intrinsic pathway complexes and MVTF, activation of FIX likely occurs through both contact/intrinsic and extrinsic pathways. Among the protease:serpin complexes measured, FIXa:AT complexes were uniquely associated with clinical indices of disease severity, specifically total length of hospitalization, length of intensive care unit stay, and extent of lung computed tomography changes. We conclude that the contact/intrinsic pathway may contribute to the pathogenesis of the prothrombotic state in COVID-19. Larger prospective studies are required to confirm whether FIXa:AT complexes are a clinically useful biomarker of adverse clinical outcomes. (© 2022 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.)
Databáze:	MEDLINE
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