Are Reduced Levels of Coagulation Proteins Upon Admission Linked to COVID-19 Severity and Mortality?

Abstract

Background: The link between coagulation system disorders and COVID-19 has not yet been fully elucidated.Aim: Evaluating the association of non-previously reported coagulation proteins with COVID-19 severity and mortality.Design: Cross-sectional study of 134 COVID-19 patients recruited at admission and classified according to the highest COVID-19 severity reached (asymptomatic/mild, moderate, or severe) and 16 healthy control individuals.Methods: Coagulation proteins levels (antithrombin, prothrombin, factor_XI, factor_XII, and factor_XIII) and CRP were measured in plasma by the ProcartaPlex Panel (Invitrogen) multiplex immunoassay upon diagnosis.Results: We found higher levels of antithrombin, prothrombin, factor XI, factor XII, and factor XIII in asymptomatic/mild and moderate COVID-19 patients compared to healthy individuals. Interestingly, decreased levels of antithrombin and factors XI, XII, and XIII were observed in those patients who eventually developed severe illness. Additionally, survival models showed us that patients with lower levels of these coagulation proteins had an increased risk of death.Conclusion: COVID-19 provokes early increments of some specific coagulation proteins in most patients. However, lower levels of these proteins at diagnosis might “paradoxically” imply a higher risk of progression to severe disease and COVID-19-related mortality.

Metabolic Profiling at COVID-19 Onset Shows Disease Severity and Sex-Specific Dysregulation

“…However, patients who will develop a severe disease could show an early difficulty in activating certain metabolic pathways compared to patients with a moderate course of the disease. Similar differential findings across the diverse severity groups, at disease onset, have been previously described for other biomarkers ( 67 ).…”

Targeting thromboinflammation in COVID-19 – A narrative review of the potential of C1 inhibitor to prevent disease progression

“…Apart from the activation of neutrophils, NETs and complement they report increased concentrations of factors XIa complexes that correlated with severity of the disease and underscore the CAS as potential driver of thromboinflammation in COVID-19 ( Busch et al, 2020 ). Increased levels of factor XI and XII at presentation were observed in another study in COVID-19 patients compared to healthy control ( Ceballos et al, 2021 ). Interestingly, patients with lower levels on admission had a higher mortality risk and this association was more pronounced in men.…”

Status of major hemostatic components in the setting of COVID-19: the effect on endothelium, platelets, coagulation factors, fibrinolytic system, and complement

“…However, as the disease progresses and after the initial elevation, FV levels decrease [ 65 ], and the activity of FV and also the activity of FVII are significantly lower in end-stage patients [ 63 ]. In FXI following a similar pattern, higher FII and FXI levels were observed in patients with asymptomatic/mild and moderate COVID-19 compared with healthy individuals, whereas lower FII and FXI levels were observed in patients with thromboembolism and in patients who developed severe disease [ 66 , 67 ].…”

“…Plts, in addition to increasing the fibrinogen and VWF, also contribute to increasing FXII in COVID-19 patients; an increased FXII activity was found when washed Plts from patients were suspended in control plasma. In addition, Ceballos et al [ 66 ] evaluated the association of antithrombin (AT), prothrombin, FXI, FXII, and FXIII with COVID-19 severity and mortality and observed higher levels of FXII in asymptomatic/mild and moderate patients compared to healthy individuals. This observation was also associated with higher levels of AT, prothrombin, FXI, and FXIII.…”

“…In addition, FXIIIa through cross-linking α2-antiplasmin to the fibrin increases resistance to fibrinolysis [ 79 ]. Ceballos et al [ 66 ] found increased FXIII in asymptomatic/mild and moderate COVID-19 patients and, interestingly, reduced FXIII in those patients who finally developed severe illness. Von Meijenfeldt et al [ 80 ], in an evaluation of FXIII activity in 97 COVID-19 patients, detected a substantial decrease in plasma FXIII activity.…”