Investigation of Coagulation Biomarkers to Assess Clinical Deterioration in SARS-CoV-2 Infection

Abstract

Since December 2019, a pandemic caused by a new coronavirus has spread to more than 170 countries around the world. Worsening infected patients requiring intensive care unit (ICU) admission associated with 30% of mortality. A part of worsening is induced by hemostasis deregulation. The aim of this study was to investigate the association of coagulation activation in COVID-19 progression. Thirty-five of the 99 patients got clinically worse. The final model of the logistic regression analysis revealed that O2 requirement (RR = 7.27 [1.50–19.31]), monocytes below 0.2G/L (RR = 2.88 [1.67–3.19]), fibrinogen levels (RR = 1.45 [1.17–1.82] per g/L increase), prothrombin fragments 1+2 higher than 290 pM (RR = 2.39 [1.20–3.30]), and thrombin peak (RR = 1.28 [1.03–1.59] per 50 nM increase) were associated with an increased risk of clinical worsening. A fibrinogen level threshold of 5.5 g/L, a thrombin peak measurement threshold of 99 pM, and O2 requirement associated with clinical outcome in more than 80% of our cohort. In conclusion, we identified fibrinogen and thrombin peak at admission as coagulation biomarkers associated with an increased risk of ICU admission or death. This finding allows initiating steroids and triage for worsening patients. Our results should therefore be considered as exploratory and deserve confirmation.

Clinical use of thrombin generation assays

“…In another study in 127 hospitalized patients with confirmed COVID‐19, ETP and LT variables correlated with thrombo‐inflammatory markers, and the D‐dimer/ETP ratio could predict major adverse events during the infection 66 . Similarly, in a prospective study in 100 hospitalized COVID‐19 patients thrombin peak at admission was found to be associated with an increased risk of ICU admission or death 67 …”

Hypercoagulability Evaluation in Antiphospholipid Syndrome without Anticoagulation Treatment with Thrombin Generation Assay: A Preliminary Study

“…However, no biomarkers have been developed to evaluate the thrombotic risk of bAPS and possibly, to initiate primary thrombosis prevention. In humans, the hypercoagulability state can be evaluated with a thrombin generation assay (TGA) [7][8][9]. Antiphospholipid syndrome has already been evaluated by TGA.…”

Routine and Advanced Laboratory Tests for Hemostasis Disorders in COVID-19 Patients: A Prospective Cohort Study

“…Our study showed a three-fold proportion of patients presenting F1 + 2 values > 500 pM in the “worsening” group. We recently described an association between increased levels of fibrinogen, thrombin generation and F1 + 2 and the need for ICU admission in patients hospitalized for SARS-CoV-2 pneumonitis in a general ward [ 18 ]. However, the results from our present study do not suggest such an association.…”

“…Finally, thrombin generation assay (TGA) is a technique that studies the initiation, propagation and inhibition of coagulation, allowing the observation of hypo- or hyper-coagulable risk profiles [ 16 , 17 ]. These three assays (F1 + 2, A-IPC and TGA) have been recently shown to be associated with the severity of COVID-19 patients and to a higher risk of intensive care unit (ICU) admission [ 15 , 18 ]. However, no study has explored the association between hematological and hemostasis markers (including A-IPC, F1 + 2 and TGA) and the worsening in organ failure during an ICU stay, nor the role of these markers as early predictors of such a worsening.…”