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. 2020 Dec 7;24(1):676.
doi: 10.1186/s13054-020-03401-8.

Thromboembolic complications in critically ill COVID-19 patients are associated with impaired fibrinolysis

Jan Matthias Kruse  1 , Abakar Magomedov  2 , Annika Kurreck  3 , Frédéric H Münch  1 , Roland Koerner  1 , Julian Kamhieh-Milz  4   5 , Andreas Kahl  1 , Inka Gotthardt  1 , Sophie K Piper  6   7 , Kai-Uwe Eckardt  1 , Thomas Dörner  8   9 , Daniel Zickler  10
Affiliations

Thromboembolic complications in critically ill COVID-19 patients are associated with impaired fibrinolysis

Jan Matthias Kruse et al. Crit Care. .

Abstract

Background: There is emerging evidence for enhanced blood coagulation in coronavirus 2019 (COVID-19) patients, with thromboembolic complications contributing to morbidity and mortality. The mechanisms underlying this prothrombotic state remain enigmatic. Further data to guide anticoagulation strategies are urgently required.

Methods: We used viscoelastic rotational thromboelastometry (ROTEM) in a single-center cohort of 40 critically ill COVID-19 patients.

Results: Clear signs of a hypercoagulable state due to severe hypofibrinolysis were found. Maximum lysis, especially following stimulation of the extrinsic coagulation system, was inversely associated with an enhanced risk of thromboembolic complications. Combining values for maximum lysis with D-dimer concentrations revealed high sensitivity and specificity of thromboembolic risk prediction.

Conclusions: The study identifies a reduction in fibrinolysis as an important mechanism in COVID-19-associated coagulopathy. The combination of ROTEM and D-dimer concentrations may prove valuable in identifying patients requiring higher intensity anticoagulation.

Keywords: COVID-19; Coagulopathy; D-dimers; Hypofibrinolysis; ROTEM.

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Conflict of interest statement

Dr. Kruse, Dr. Magomedov, Dr. Kurreck, Dr. Münch, Dr. Koerner, Dr. Kamhieh-Milz, Dr. Kahl, Dr. Piper and Dr. Dörner have nothing to disclose. Dr. Eckardt reports personal fees from Akebia, grants from Amgen, grants from Astra Zeneca, grants and personal fees from Bayer, grants from Fresenius, from Genzyme, from Shire and grants and personal fees from Vifor, outside the submitted work. Dr. Zickler reports grants and personal fees from Baxter, outside the submitted work.

Figures

Fig. 1
Fig. 1
a All measured values in ROTEM analysis, including clotting time (CT [s]), clot formation time (CFT [s]), maximum clot firmness (MCF [mm]) and maximum lysis (ML [%(range)]). b A reduction of fibrinolysis in a COVID-19 patient with a thromboembolic event; the clot amplitude remains unchanged until the end. c A physiological fibrinolysis pattern in a healthy person, reflected by the subtle decrease of the MCF during the measurement
Fig. 2
Fig. 2
a Maximum lysis (ML) in EXTEM, b maximum lysis (ML) in INTEM, c D-dimers on the day of ROTEM and d max. CRP in COVID-19 patients with and without thromboembolic complications
Fig. 3
Fig. 3
ROC analysis of a maximum lysis (ML) in EXTEM, b D-dimer and c ML INTEM d difference of ML in EXTEM and max. D-dimer for prediction of thromboembolic events in our cohort [*AUC of 0·92 (p < 0.001)]
See this image and copyright information in PMC

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