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Involvement of The Contact Pathway in COVID-19 Coagulopathy

1Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milano, Lombardia, Italy, 2Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico , Milan, Lombardia, Italy, 3Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Milano, Lombardia, Italy, 4Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy, Milano, Lombardia, Italy, 5Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Transfusion Medicine and Hematology and Università degli Studi di Milano, Department of Pathophysiology and Transplantation, Milano, Lombardia, Italy, 6Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Transfusion Medicine and Hematology, Milano, Lombardia, Italy, 7Fondazione 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, 8Fondazione 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, 9Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Università degli Studi di Milano, Department of Pathophysiology and Transplantation, and Fondazione Luigi Villa, Milan, Italy., Milan, Lombardia, Italy

Abstract Number: PB0584

Meeting: ISTH 2022 Congress

Theme: COVID and Coagulation » COVID and Coagulation, Basic Science

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.

Table

Table. Demographic and clinical characteristics of patients and controls.
* All patients had a venous thrombosis, and one patient had an ischemic stroke together with a venous thrombosis.

image

Figure. Box plots of the markers of extrinsic -FXIIa- and contact pathway -FXIa, FXIIa, C1-INH- of the coagulation cascade in controls and the COVID-19 patients in the three intensity of care levels. On the x axis are reported the patients’ categories -0, healthy controls; 1, low-intensity of care COVID-19 patients; 2, intermediate-intensity of care COVID-19 patients; 3, high-intensity of care COVID-19 patients-, while on the y axis plasma levels of the tested parameters are reported -mU/mL for FXIa, FXIIa, FVIIa, and % for C1-INH-.

To cite this abstract in AMA style:

Capecchi M, Novembrino C, Abbattista M, Boscolo M, Griffini S, Grovetti E, Artoni A, Valenti L, Prati D, Grasselli G, Blasi F, Cugno M, Peyvandi F. Involvement of The Contact Pathway in COVID-19 Coagulopathy [abstract]. https://abstracts.isth.org/abstract/involvement-of-the-contact-pathway-in-covid-19-coagulopathy/. Accessed September 27, 2023.

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