Serial EXTEM, FIBTEM, and tPA Rotational Thromboelastometry Observations in the Maastricht Intensive Care COVID Cohort-Persistence of Hypercoagulability and Hypofibrinolysis Despite Anticoagulation.

Anne-Marije Hulshof,Hugo Ten Cate,Tom W Van De Berg,Paul Verhezen,Alexander S Streng,Bas C T Van Bussel,Renske H Olie,Jan-Willem E M Sels,Iwan C C Van Der Horst,Mark M G Mulder,Bart Spaetgens,Henri M H Spronk,Renée A G Brüggemann,Yvonne M C Henskens

doi:10.3389/fcvm.2021.654174

Abstract

Background: Coronavirus Disease 2019 (COVID-19) patients often present with thromboembolic events. In COVID-19 patients, routine hemostatic assays cannot correctly identify patients at risk for thromboembolic events. Viscoelastic testing with rotational thromboelastometry (ROTEM) might improve the characterization of COVID-19-associated coagulopathy.Objective: To unravel underlying coagulopathy and fibrinolysis over time as measured by serial assessment heparin-independent (FIBTEM and EXTEM) and fibrinolysis illustrating (tissue plasminogen activator; tPA) ROTEM assays.Patients/Methods: Between April 23 and June 12, consecutive adult patients enrolled within the Maastricht Intensive Care COVID (MaastrICCht) cohort were included, and a comprehensive set of clinical, physiological, pharmaceutical, and laboratory variables were collected daily. Twice per week, EXTEM, FIBTEM, and tPA ROTEM were performed. Clotting time (CT), clot formation time (CFT), maximum clot firmness (MCF), lysis onset time (LOT), and lysis time (LT) were determined to assess clot development and breakdown and were compared to routine hemostatic assays.Results: In 36 patients, 96 EXTEM/FIBTEM and 87 tPA ROTEM tests were performed during a 6-week follow-up. CT prolongation was present in 54% of EXTEM measurements, which were not matched by prothrombin time (PT) in 37%. Respectively, 81 and 99% of all EXTEM and FIBTEM MCF values were above the reference range, and median MCF remained elevated during follow-up. The ROTEM fibrinolysis parameters remained prolonged with median LOT consequently >49 min and unmeasurable LT in 56% of measurements, suggesting a severe hypofibrinolytic phenotype.Conclusion: ROTEM tests in COVID-19 ICU patients show hypercoagulability and severe hypofibrinolysis persisting over at least 6 weeks.

Highlights

MATERIALS AND METHODSEarly after the onset of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, anecdotal reports of COVID-19 patients suffering from extensive thromboembolic complications, mainly pulmonary embolisms, emerged [1, 2]
Thirty-six COVID-19 intensive care unit (ICU) patients were included in the present study
Our serial and comprehensive study to characterize COVID19-associated coagulopathy by thromboelastometry has four main findings: [1] a persisting increase in MCF that was more prominent in FIBTEM compared to EXTEM, illustrating hypercoagulability that is at least partly fibrinogen dependent; [2] a prolonged EXTEM CT in 54% of all measurements; [3] a discordance between EXTEM CT and PT observed in 37% of the samples, possibly suggesting missing coagulopathy recognition in routine hemostatic assays; and [4] a persistently increased lysis onset time (LOT) and lysis time (LT) measured with tPA rotational thromboelastometry (ROTEM), illustrating hypofibrinolysis

Summary

Background

Coronavirus Disease 2019 (COVID-19) patients often present with thromboembolic events. In COVID-19 patients, routine hemostatic assays cannot correctly identify patients at risk for thromboembolic events. Viscoelastic testing with rotational thromboelastometry (ROTEM) might improve the characterization of COVID-19-associated coagulopathy

Objective

Results

MATERIALS AND METHODS

RESULTS

DISCUSSION

ETHICS STATEMENT