ABSTRACT
Background: The coagulation system showed significant variations in COVID-19 patients. These variations may parallel the disease stage of COVID-19 toward either a hyper-activation or coagulopathy syndrome. Classical clotting tests assist in exploring coagulation disorders, but they are unsuitable to examine prothrombotic conditions. In this regard, thrombin generation assay helps for a global assessment of the coagulation process, being appropriate for investigating hypercoagulable states and bleeding tendency. Aim(s): It was investigated whether thrombin generation assay reveals coagulation variations in COVID-19 patients by a care setting design. Method(s): From October to December 2020, it have been enrolled 27 and 40 patients with a confirmed COVID-19 diagnosis who were hospitalised in an Intensive Care Unit (ICU) and a Medical Ward (MW), respectively. Also, 34 healthy subjects were included in this study. Thrombin generation parameters were evaluated using a Calibrated Automated Thrombogram system. Informed consent and approval by the local medical Ethics Committee were obtained. Result(s): Lag-Time and time-to- peak found in ICU and MW patients were significantly higher than those found in healthy subjects (Kruskal-Wallis test: P < 0.0001). Endogenous-Thrombin- Potential and thrombin-peak observed in ICU and MW patients were significantly lower than those observed in healthy subjects (Kruskal-Wallis test: P < 0.0001). No statistically significant differences in all the parameters measured were observed between ICU and MW patients. Conclusion(s): Thrombin generation assay performed in this study evidenced an acquired coagulopathy in COVID-19 patients that, however, seems to be unrelated to the care setting and, in turn, to the clinical disease severity.
ABSTRACT
Background: High von Willebrand factor (VWF)/ADAMTS13 fraction might reflect endothelial dysfunction observed in serious COVID-19. Aims: 1) To compare VWF/ADAMTS13 fraction by care setting and explore correlation of this parameter with some routine blood parameters;2) To prospectively evaluate whether and to what extent variations in VWF/ADAMTS13 fraction can be predictive of fatalities. Methods: VWF/ADAMTS13 fraction were compared by care setting (Intensive Care Unit -ICU-vs. Medical Ward -MW-). The study included 22 and 52 patients admitted to ICU and MW, respectively. For 54 patients, we collected also a blood sample at an interval of five days from the first one and prospectively investigated relationship in dynamic changes between VWF/ADAMTS13 fraction and routine blood parameters. Continuous variables were reported as median (IQR). Parametric and non-parametric tests were used according to value distribution and χ2 test to compare variables in a contingency table. The Area-Under-Curve (AUC) was calculated. The p values < 0.05 set the statistical significance. Results: Patients admitted to the ICU were significantly younger [63.0 (15.2) vs. 69.0 (19.7), P = 0.03 ] and mostly males (M/F: 17/5 vs. 26/29). Fatalities were similar in the two care settings (45.5% in ICU vs. 30.7% in MW, Fisher's Test: P = 0.19). Moreover, VWF:RCo/ ADAMTS13 fraction of 5.7 was predictive of ICU admission [AUC = 0.81 (0.70-0.92), p<0.001 ]. Overall, at admission, VWF:RCo/ ADAMTS13 fraction directly correlated with C-reactive protein (CRP) (Spearman r: 0.51, P < 0.0001 ). This relationship was observed also in the prospective cohort ( n = 54) (Spearman r: 0.54, P = 0.0014 ) and independently of the care setting (in ICU: P = 0.006 in MW: P = 0.02 ) and was maintained throughout the entire period of hospitalization. Cut-off of 6.5 in VWF:RCo/ADAMTS13 was associated with in-hospital death (AUC: 0.71, P = 0.003 ). Conclusions: VWF:RCo/ADAMTS13 fraction seems to be a good predictor of ICU admission and in-hospital mortality. This study also shows that during COVID-19, CRP directly correlates with endothelial dysfunction.