PB0593 - Increased Percentage of Extended Aα Chain Fibrinogen (αE) in COVID-19 Patients

Monday, July 11, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

Judith J. de Vries, MSc

PhD student
Department of Hematology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands
Rotterdam, Zuid-Holland, Netherlands

Co-Author(s)

Chantal Visser, MD

PhD candidate, MD
Department of Hematology, Erasmus MC, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands
Rotterdam, Zuid-Holland, Netherlands
Mv

Maureen van Ommen

Senior Research Assistant
Fibriant B.V.
Leiden, Zuid-Holland, Netherlands
CR

Casper Rokx

Medical Specialist
Department of Medical Microbiology and Infectious Diseases, Erasmus MC, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands
Rotterdam, Zuid-Holland, Netherlands
Ev

Els van Nood

Medical Specialist
Department of Medical Microbiology and Infectious Diseases, Erasmus MC, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands
Rotterdam, Zuid-Holland, Netherlands
Ev

Eric C. van Gorp

Professor
Department of Internal Medicine & Department of Viroscience, Erasmus MC, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands
Rotterdam, Zuid-Holland, Netherlands
MG

Marco Goeijenbier

Post-doc
Department of Viroscience & Department of Adult Intensive Care, Erasmus MC, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands
Rotterdam, Zuid-Holland, Netherlands
Jv

Johannes P. van den Akker

Medical Specialist
Department of Adult Intensive Care, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands
Rotterdam, Zuid-Holland, Netherlands
HE

Henrik Endeman

Medical Specialist
Department of Adult Intensive Care, Erasmus Medical Center Rotterdam, Rotterdam, the Netherlands
Rotterdam, Zuid-Holland, Netherlands
DR

Dingeman C. Rijken

Associate Professor
Department of Hematology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands
Rotterdam, Zuid-Holland, Netherlands
MK

Marieke J.H.A. Kruip

Associate professor, hematologist, MD, PhD
Department of Hematology, Erasmus MC, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands
Rotterdam, Zuid-Holland, Netherlands
MW

Miranda Weggeman

Chief Technology Officer
Fibriant B.V.
Leiden, Zuid-Holland, Netherlands
JK

Jaap Koopman

Chief Executive Officer
Fibriant B.V.
Leiden, Zuid-Holland, Netherlands
Moniek P.M. de Maat, PhD

Professor
Department of Hematology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands
Rotterdam, Zuid-Holland, Netherlands

Background: Variation in fibrinogen caused by degradation or extension of the Aα chain affects the fibrin network structure and interaction of fibrin(ogen) with cells. The plasma level of these fibrinogen variants might be altered during COVID-19, potentially affecting disease severity or the risk of thrombosis.

Aims: To investigate the level of fibrinogen Aα chain variants in plasma of COVID-19 patients.

Methods: Using the Clauss assay, we measured plasma levels of functional fibrinogen. ELISAs were used to measure antigen levels of total, intact (non-degraded Aα chain), and extended Aα chain fibrinogen (αE) in intensive care unit (ICU) patients with COVID-19 (with and without thrombosis, at two time points), COVID-19 ward patients without thrombosis, ICU patients with pneumococcal infection, and healthy controls. Ethical approval was obtained and written informed consent was obtained or an opt-out procedure was in place.

Results: Higher levels of functional and intact fibrinogen were observed in COVID-19 ICU patients (before diagnosis of thrombosis) with (n=18) and without thrombosis (n=19) and ICU patients with pneumococcal infection (n=6) than in COVID-19 ward patients (n=10) and healthy controls (n=7) (Figure 1). Total fibrinogen levels were higher in all ICU patients compared to healthy controls. Interestingly, the percentage of αE fibrinogen was significantly higher in COVID-19 ICU patients who do and do not develop thrombosis than in healthy controls. COVID-19 ICU patients who develop thrombosis also showed significantly higher percentages of αE fibrinogen than COVID-19 ward patients. After diagnosis of thrombosis, functional fibrinogen levels were significantly higher in COVID-19 ICU patients with thrombosis than in those without, while no differences were observed in intact, total, or αE fibrinogen (Figure 2).

Conclusion(s): Our results show that severe COVID-19 is associated with increased percentages of αE fibrinogen, which may be the cause or consequence of severe disease, but does not explain the development of thrombosis.