Enhanced prothrombotic state in patients with severe COVID-19

Objective An infection with the novel SARS-CoV-2 virus is accompanied with thrombosis and pulmonary embolism. Comorbidities, like hypertension, diabetes, coronary heart disease, are associated with high mortality. Viral infections as well as above mentioned comorbidity induce an activation of the coagulation system, especially recognizable by increased levels of D-dimer. Here, we present data of COVID-19 patients in comparison to non-COVID-19 patients treated in an intensive care unit.

Material and Methods 24 patients with COVID-19 were included in this study. As a control group, 33 patients treated in the same the intensive care unit with symptoms of upper respiratory infections both negative COVID-19 test were included. Both groups were included between March and May 2020 and show no differences in regard to age and gender. Enzygnost F1+2 (prothrombin fragments), INNOVANCE D-Dimer and INNOVANCE Anti-Xa (all Siemens Healthineers) and Thrombinscope’s CAT assay (Calibrated Automated Thrombogram, expressed as thrombin peak) were performed according to manufacturer’s instructions.

Results Significant differences between the groups were observed in for the activation marker D-dimer. Non-significant differences were observed for prothrombin fragments and thrombin peak, nevertheless indicating an enhanced prothrombotic state in COVID-19 patients (n=24) compared to non-COVID-19 patients (n=33): prothrombin fragments F1+2 (nM): 405 ± 299 vs. 290 ± 211 (p=0,09); D-dimer (mg/L): 1,9 ± 1,4 vs. 1,2 ± 1,1 (p=0,04); thrombin peak (nM): 324 ± 110 vs. 293 ± 108 (p=0,29).

In samples containing less than 0,25 IU/mL heparin (21 COVID-19, 31 controls), similar results were achieved: prothrombin fragments F1+2 (nM): 426 ± 310 vs. 289 ± 213 (p=0,07); D-dimer (mg/L): 1,9 ± 1,5 vs. 1,2 ± 1,1 (p=0,05); thrombin peak (nM): 339 ± 105 vs. 311 ± 82 (p=0,29).

Conclusion In patients with a severe COVID-19 infection, the coagulation system is strongly activated. The observed imbalance promotes thromboembolism and might result in multi-organ failure. More data are required to strengthen the observed results. Additionally, other methods like fully-automated thrombin generation and clot waveform analysis should be included.

Publication History

Article published online:
18 June 2021