Among patients diagnosed with coronavirus disease 2019 (COVID-19), the contact/intrinsic pathway may have a causal link with pathogenesis of the prothrombotic state, according to research published in Blood Advances. Furthermore, it may be that microvesicle tissue factor (MVTF)-mediated factor Xa (FXa):antithrombin (AT) complexes may be linked with poor outcomes in this setting.

Previous research has suggested that coagulation pathways play a crucial role in the pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19. Specifically, alterations of coagulation biomarkers have been linked with severe disease, venous thromboembolism, and pulmonary microvascular thrombi.

It was, however, previously unclear how specific complexes, such as FXa:AT, affect SARS-CoV-2 pathogenesis. For this study, researchers aimed to elucidate mechanisms of coagulation activation among a cohort of patients with COVID-19. The researchers also aimed to determine any link between these biomarkers and clinical outcomes in the setting of COVID-19.


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Data from a cohort of 30 patients were compared with those of 30 volunteer participants without COVID-19. In the COVID-19 and volunteer cohorts, the mean ages were 52.7 and 50.3 years, respectively, and the male:female sex ratios were both 16:14. In the COVID-19 group, the mean length of hospital stay was 12.9 days, and 6.7% of patients died.

All patient samples were taken within 24 hours of COVID-19 diagnosis. Analysis showed that, in patients with COVID-19, contact system and intrinsic pathway activation was noted by increased plasma levels of FXIIa:C1 esterase inhibitor (C1), kallikrein:C1, FXIa:C1, FXIa:a1-antitrypsin, and FIXa:AT. MVTF levels were also elevated in the patient samples.

Notably, FIXa:AT complexes were directly linked with disease severity, including length of hospitalization, length of intensive care unit stay, and degree of changes in lung computed tomography.

“We conclude that the contact/intrinsic pathway may contribute to the pathogenesis of the prothrombotic state in COVID-19,” the authors wrote in their report. “Larger prospective studies are required to confirm whether FIXa:AT complexes are a clinically useful biomarker of adverse clinical outcomes.”

Reference

Henderson MW, Lima F, Moraes CRP, et al. Contact and intrinsic coagulation pathways are activated and associated with adverse clinical outcomes in COVID-19. Blood Adv. 2022;6(11):3367-3377. doi:10.1182/bloodadvances.2021006620