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Suppression of Fibrinolysis and Hypercoagulability, Severity of Hypoxemia, and Mortality in COVID-19 Patients: A Retrospective Cohort Study.

Publication ,  Journal Article
Corey, KM; Olson, LB; Naqvi, IA; Morrison, SA; Davis, C; Nimjee, SM; Que, LG; Bachelder, RE; Kraft, BD; Chen, L; Nair, SK; Levy, JH; Sullenger, BA
Published in: Anesthesiology
July 1, 2022

BACKGROUND: COVID-19 causes hypercoagulability, but the association between coagulopathy and hypoxemia in critically ill patients has not been thoroughly explored. This study hypothesized that severity of coagulopathy would be associated with acute respiratory distress syndrome severity, major thrombotic events, and mortality in patients requiring intensive care unit-level care. METHODS: Viscoelastic testing by rotational thromboelastometry and coagulation factor biomarker analyses were performed in this prospective observational cohort study of critically ill COVID-19 patients from April 2020 to October 2020. Statistical analyses were performed to identify significant coagulopathic biomarkers such as fibrinolysis-inhibiting plasminogen activator inhibitor 1 and their associations with clinical outcomes such as mortality, extracorporeal membrane oxygenation requirement, occurrence of major thrombotic events, and severity of hypoxemia (arterial partial pressure of oxygen/fraction of inspired oxygen categorized into mild, moderate, and severe per the Berlin criteria). RESULTS: In total, 53 of 55 (96%) of the cohort required mechanical ventilation and 9 of 55 (16%) required extracorporeal membrane oxygenation. Extracorporeal membrane oxygenation-naïve patients demonstrated lysis indices at 30 min indicative of fibrinolytic suppression on rotational thromboelastometry. Survivors demonstrated fewer procoagulate acute phase reactants, such as microparticle-bound tissue factor levels (odds ratio, 0.14 [0.02, 0.99]; P = 0.049). Those who did not experience significant bleeding events had smaller changes in ADAMTS13 levels compared to those who did (odds ratio, 0.05 [0, 0.7]; P = 0.026). Elevations in plasminogen activator inhibitor 1 (odds ratio, 1.95 [1.21, 3.14]; P = 0.006), d-dimer (odds ratio, 3.52 [0.99, 12.48]; P = 0.05), and factor VIII (no clot, 1.15 ± 0.28 vs. clot, 1.42 ± 0.31; P = 0.003) were also demonstrated in extracorporeal membrane oxygenation-naïve patients who experienced major thrombotic events. Plasminogen activator inhibitor 1 levels were significantly elevated during periods of severe compared to mild and moderate acute respiratory distress syndrome (severe, 44.2 ± 14.9 ng/ml vs. mild, 31.8 ± 14.7 ng/ml and moderate, 33.1 ± 15.9 ng/ml; P = 0.029 and 0.039, respectively). CONCLUSIONS: Increased inflammatory and procoagulant markers such as plasminogen activator inhibitor 1, microparticle-bound tissue factor, and von Willebrand factor levels are associated with severe hypoxemia and major thrombotic events, implicating fibrinolytic suppression in the microcirculatory system and subsequent micro- and macrovascular thrombosis in severe COVID-19.

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Published In

Anesthesiology

DOI

EISSN

1528-1175

Publication Date

July 1, 2022

Volume

137

Issue

1

Start / End Page

67 / 78

Location

United States

Related Subject Headings

  • Thrombosis
  • Thromboplastin
  • Thrombophilia
  • Retrospective Studies
  • Respiratory Distress Syndrome
  • Prospective Studies
  • Plasminogen Activator Inhibitor 1
  • Oxygen
  • Microcirculation
  • Hypoxia
 

Citation

APA
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Corey, K. M., Olson, L. B., Naqvi, I. A., Morrison, S. A., Davis, C., Nimjee, S. M., … Sullenger, B. A. (2022). Suppression of Fibrinolysis and Hypercoagulability, Severity of Hypoxemia, and Mortality in COVID-19 Patients: A Retrospective Cohort Study. Anesthesiology, 137(1), 67–78. https://doi.org/10.1097/ALN.0000000000004239
Corey, Kristin M., Lyra B. Olson, Ibtehaj A. Naqvi, Sarah A. Morrison, Connor Davis, Shahid M. Nimjee, Loretta G. Que, et al. “Suppression of Fibrinolysis and Hypercoagulability, Severity of Hypoxemia, and Mortality in COVID-19 Patients: A Retrospective Cohort Study.Anesthesiology 137, no. 1 (July 1, 2022): 67–78. https://doi.org/10.1097/ALN.0000000000004239.
Corey KM, Olson LB, Naqvi IA, Morrison SA, Davis C, Nimjee SM, et al. Suppression of Fibrinolysis and Hypercoagulability, Severity of Hypoxemia, and Mortality in COVID-19 Patients: A Retrospective Cohort Study. Anesthesiology. 2022 Jul 1;137(1):67–78.
Corey, Kristin M., et al. “Suppression of Fibrinolysis and Hypercoagulability, Severity of Hypoxemia, and Mortality in COVID-19 Patients: A Retrospective Cohort Study.Anesthesiology, vol. 137, no. 1, July 2022, pp. 67–78. Pubmed, doi:10.1097/ALN.0000000000004239.
Corey KM, Olson LB, Naqvi IA, Morrison SA, Davis C, Nimjee SM, Que LG, Bachelder RE, Kraft BD, Chen L, Nair SK, Levy JH, Sullenger BA. Suppression of Fibrinolysis and Hypercoagulability, Severity of Hypoxemia, and Mortality in COVID-19 Patients: A Retrospective Cohort Study. Anesthesiology. 2022 Jul 1;137(1):67–78.

Published In

Anesthesiology

DOI

EISSN

1528-1175

Publication Date

July 1, 2022

Volume

137

Issue

1

Start / End Page

67 / 78

Location

United States

Related Subject Headings

  • Thrombosis
  • Thromboplastin
  • Thrombophilia
  • Retrospective Studies
  • Respiratory Distress Syndrome
  • Prospective Studies
  • Plasminogen Activator Inhibitor 1
  • Oxygen
  • Microcirculation
  • Hypoxia