| Autor: |
Michael W. Henderson, Franciele Lima, Carla Roberta Peachazepi Moraes, Anton Ilich, Stephany Cares Huber, Mayck Silva Barbosa, Irene Santos, Andre C. Palma, Thyago Alves Nunes, Raisa Gusso Ulaf, Luciana Costa Ribeiro, Ana Flavia Bernardes, Bruna Bombassaro, Sergio San Juan Dertkigil, Maria Luiza Moretti, Sidney Strickland, Joyce M. Annichino-Bizzacchi, Fernanda Andrade Orsi, Eli Mansour, Licio A. Velloso, Nigel S. Key, Erich Vinicius De Paula |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
Blood advances. 6(11) |
| ISSN: |
2473-9537 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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