ABSTRACT
Introduction: A significant degree of mortality and morbidity in COVID-19 is due to thromboembolic disease. Changes in coagulation markers have been well described in critically unwell patients on ICU. There is less clear evidence regarding these changes at the time of presentation to the Emergency Department and the progression of disease over time. We sought to investigate how coagulation markers change over the course of COVID-19 infection and whether they might predict disease severity. Methods: Patients were recruited from a single University Teaching Hospital ED at the time of presentation. Those with a positive PCR test were followed up throughout their stay. Rotational thromboelastometry (ROTEM) was performed on arrival, after 24 h, 3-5 days and 7 days, alongside routine haematological and biochemical testing. ROTEM values at each of these time points were analysed, and compared. Length of stay and patient outcome were also recorded for subgroup analysis. The ROTEM parameters selected for analysis were both EXTEM and INTEM Clotting Time (CT), Clot Formation Time (CFT), Maximal Clot Firmness (MCF), Alpha Angle (Alpha) and Maximum Lysis Percentage (ML). This reflects clot formation kinetics, mechanical strength and clot breakdown via both extrinsic and intrinsic pathways. Results: EXTEM (7.64 ± 5.53 vs 11.83 ± 6.30) and INTEM ML (4.69 ± 3.55 vs 9.95 ± 5.22) were significantly reduced in those who died vs patients with a prolonged hospital stay. Over time there were no patterns of change to ROTEM values in any outcome group. Conclusions: Comparisons between groups demonstrated that one distinguishing feature between those who require ICU admission or die of COVID-19 compared with those who survive a prolonged hospital stay to discharge was the extent to which fibrinolysis could occur. Failure to break clots down could be a significant mechanism in the mortality and morbidity of COVID-19.
ABSTRACT
Introduction: A significant degree of mortality and morbidity in COVID-19 is due to thromboembolic disease. We use viscoelastic testing to investigate changes to coagulation profile over the progression of COVID-19 infection. Methods: Patients presenting to a single large University Teaching Hospital ED were recruited at presentation. Those with positive COVID- 19 PCR test were included for analysis. Whole blood samples were taken for viscoelastic tests. Fractal Dimension ( Df) and Time to Gel Point ( TGP) are biomarkers of thrombogenicity which measure the biomechanical properties of the incipient clot [1]. Patients were followed up throughout their hospital stay, with sampling taken at arrival, after 24 h, 3-5 days and 7 days. Length of stay and patient outcome were recorded and used for subgroup analysis. Once admitted to the hospital all patients received low molecular weight heparin (LMWH) as per standard treatment pathways, if commenced before the first sample was taken, this was recorded and controlled for. Results: Df and TGP showed no changes over time in COVID-19 infection. Subgroup analysis also showed no differences in Df or TGP in different outcome groups. Patients who received LMWH from the clinical team before recruitment to the study demonstrated no significant difference in Df (1.715 ± 0.061 no LMWH vs 1.699 ± 0.068 with LMWH), but TGP was prolonged in those receiving LMWH(445.0 ± 195.2 vs 307.6 ± 91.6). Additionally there was no correlation between Anti-Xa level and Df. Conclusions: The therapeutic efficacy of LMWH appears to be blunted in COVID-19 infection. This may be due to the inflammatory state creating a resistance to the activity of LMWH, and may in part explain why LMWH appears to have less effect in reducing thromboembolic disease in COVID-19 than it does in other disease states.