Hypercoagulation Detected by Rotational Thromboelastometry Predicts Mortality in COVID-19: A Risk Model Based on a Prospective Observational Study

Abstract

Background Severe disease due to the novel coronavirus disease 2019 (COVID-19) has been shown to be associated with hypercoagulation. The aim of this study was to assess the Rotational Thromboelastometry (ROTEM) as a marker of coagulopathy in hospitalized COVID-19 patients. Methods This was a prospective, observational study where patients hospitalized due to a COVID-19 infection were eligible for inclusion. Conventional coagulation tests and ROTEM were taken after hospital admission, and patients were followed for 30 days. A prediction model, including variables ROTEM EXTEM-MCF (Maximum Clot Firmness) which in previous data has been suggested a suitable marker of hypercoagulation, age, and respiratory frequency, was developed using logistic regression to evaluate the probability of death. Results Out of the 141 patients included, 18 (13%) died within 30 days. In the final prediction model, the risk of death within 30 days for a patient hospitalized due to COVID-19 was increased with increased EXTEM-MCF, age, and respiratory frequency. Longitudinal ROTEM data in the severely ill subpopulation showed enhanced hypercoagulation. In an in vitro analysis, no heparin effect on EXTEM-coagulation time (CT) was observed, supporting a severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) effect on prolonged initiation of coagulation. Conclusion Here, we show that hypercoagulation measured with ROTEM predicts 30-day mortality in COVID-19. Longitudinal ROTEM data strengthen the hypothesis of hypercoagulation as a driver of severe disease in COVID-19. Thus, ROTEM may be a useful tool to assess disease severity in COVID-19 and could potentially guide anticoagulation therapy.

Keywords: COVID-19; coagulopathy; mortality; thromboelastometry; thrombosis.

Fig. 1

Predicted probability of death vs risk score. Distribution of patients across range of risk scores, corresponding to the logit (logged odds ratio) calculated using logistical regression with the three predictor variables at inclusion (EXTEM-MCF, age, and respiratory frequency). The histogram in black, presented in the lower part of the figure, shows the distribution of risk scores in the present data (e.g., 12 patients have a risk score of 0, translating to approximately 50% probability of dying within 30 days). MCF, maximum clot firmness.

Fig. 2

Longitudinal ROTEM data. ROTEM sampled at inclusion, after 5 days and after 10 days. In ( A ) EXTEM- MCF (dashed horizontal lines are upper and lower reference values: 50–72 mm); ( B ) EXTEM-CT (dashed horizontal line is upper reference value: 79 second); ( C ) EXTEM-CFT (dashed horizontal line is lower reference value: 34 second). Median values reported with error bars representing IQR. For visualization purposes some outliers are not shown but are represented by lines connecting them to follow up measurements. Abbreviations: CFT, clot formation time; CT, coagulation time; EXTEM, extrinsically activated assays with tissue factor; IQR, interquartile range; MCF, maximum clot firmness; ROTEM, Rotational Thromboelastometry.