PB0584 - Involvement of The Contact Pathway in COVID-19 Coagulopathy

Monday, July 11, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Co-Author(s)

MC

Marco Capecchi, MD

MD
Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy
Milan, Lombardia, Italy
Cristina Novembrino, PhD

BSc
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy
Milan, Lombardia, Italy

Presenting Author(s)

Maria Abbattista, PhD

Clinical Researcher
Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Centro Emofilia e Trombosi Angelo Bianchi Bonomi
Milan, Lombardia, Italy

Co-Author(s)

MB

Massimo Boscolo

MSc in biology
Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center
Milano, Lombardia, Italy
SG

Samantha Griffini

msc in biology
Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center
Milano, Lombardia, Italy
EG

Elena Grovetti

Msc in biology
Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center
Milano, Lombardia, Italy
Andrea Artoni, MD

MD
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy
Milano, Lombardia, Italy
LV

Luca Valenti

Medical Doctor
Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Transfusion Medicine and Hematology and Università degli Studi di Milano, Department of Pathophysiology and Transplantation
Milano, Lombardia, Italy
DP

Daniele Prati

Medical Doctor
Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Transfusion Medicine and Hematology
Milano, Lombardia, Italy
GG

Giacomo Grasselli

Medical Doctor
Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Department of Anesthesia Intensive Care and Emergency and Università degli Studi di Milano, Department of Pathophysiology and Transplantation
Milano, Lombardia, Italy
FB

Francesco Blasi

Medical Doctor
Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Respiratory Unit and Cystic Fibrosis Adult Center and Università degli Studi di Milano, Department of Pathophysiology and Transplantation
Milano, Lombardia, Italy
MC

Massimo Cugno

Medical Doctor
Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center
Milano, Lombardia, Italy
Flora Peyvandi, MD, PhD

Professor of Internal Medicine; Director of the Angelo Bianchi Bonomi Hemophilia & Thrombosis Center
Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
Milan, Lombardia, Italy

Background: A novel acquired coagulopathy characterized by a severe procoagulant imbalance is common in COVID-19 patients and is associated with the clinical severity of the disease.

Aims: Our study aims to elucidate the underlying mechanisms of coagulation activation in COVID-19 patients.

Methods: Symptomatic COVID-19 patients during Milan first wave were consecutively enrolled and stratified into 3 groups based on the intensity of care: low, requiring only high-flow oxygen by nasal cannula; intermediate, requiring continuous positive airway pressure; high, requiring mechanical ventilation. Blood samples were tested for markers of activation of the intrinsic pathway (FXIa, FXIIa) together with its physiologic inhibitor (C1-inhibitor), of the extrinsic pathway (FVIIa), of global activation of the coagulation cascade (D-dimer, FDP, FM) and of fibrinolysis (plasminogen, t-PA, 𝛼2-antiplasmin, PAI-1).

Results: 111 patients were included: 26 at low, 42 intermediate and 43 high care-intensity. Median age was 5912 (34 patients >65 years); 32 patients (29%) developed a venous thrombosis and 12 (11%) died (Table). Median D-dimer, FDP and FM plasma levels were higher in COVID-19 patients compared to controls, with a gradient of increase across the three care intensities, while all the fibrinolytic pathway parameters were in the normal range. Median plasma levels of FVIIa were lower in COVID-19 patients (27.5 mU/mL) than in controls (40.1 mU/mL) while median plasma levels of FXIIa and FXIa were higher in COVID-19 patients (11.2 and 11.3 mU/mL) than in controls (7.2 and 5.5 mU/mL), with a gradient of increase across the three care intensities. C1-inhibitor plasma levels were above the normal range in all the 3 COVID-19 patients’ groups (Figure).

Conclusion(s): Our study showed a prevalent activation of the contact pathway over the extrinsic pathway of the coagulation cascade in COVID-19 patients, which is proportional to the clinical severity of the infection, opening the possibility for targeted anticoagulant therapies.