Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Aug:12:100140.
doi: 10.1016/j.tru.2023.100140. Epub 2023 Jun 7.

Applications of rotational thromboelastometry in heparin monitoring in critical COVID-19 disease: Observations in the Maastricht Intensive Care COVID cohort

Affiliations

Applications of rotational thromboelastometry in heparin monitoring in critical COVID-19 disease: Observations in the Maastricht Intensive Care COVID cohort

Lejan Schultinge et al. Thromb Update. 2023 Aug.

Abstract

Background: Critically ill COVID-19 patients are at risk for venous thromboembolism (VTE). Therefore, they receive thromboprophylaxis and, when appropriate, therapeutic unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). To monitor heparins in COVID-19 disease, whole-blood rotational thromboelastometry (ROTEM) may be a promising alternative to the aPTT and anti-Xa assays.

Objective: To evaluate the ROTEM INTEM/HEPTEM ratios in mechanically ventilated COVID-19 patients treated with UFH and therapeutic LMWH.

Material and methods: A subcohort of mechanically ventilated COVID-19 patients of the prospective Maastricht Intensive Care Covid (MaastrICCht) cohort was studied. Anti-Xa, aPTT, and ROTEM measurements following treatment with UFH or therapeutic dose of LMWH (nadroparin) were evaluated using uni- and multivariable linear regression analysis and receiver operating characteristics.

Results: A total of 98 patients were included, of which 82 were treated with UFH and 16 with therapeutic LMWH. ROTEM-measured INTEM/HEPTEM CT ratio was higher in patients using UFH (1.4 [1.3-1.4]) compared to patients treated with LMWH (1.0 [1.0-1.1], p < 0.001). Both the aPTT and anti-Xa were associated with the CT ratio. However, the β-regression coefficient (95%CI) was significantly higher in patients on UFH (0.31 (0.001-0.62)) compared to therapeutic LMWH (0.09 (0.05-0.13)) for comparison with the anti-Xa assay. Furthermore, ROC analysis demonstrated an area under the curve for detecting UFH of 0.936(0.849-1.00), 0.851(0.702-1.000), and 0.645(0.465-0.826) for the CT ratio, aPTT, and anti-Xa, respectively.

Conclusion: The ROTEM INTEM/HEPTEM CT ratio appears a promising tool to guide anticoagulant therapy in ICU patients with COVID-19 disease, but associations with clinical endpoints are currently lacking.

Keywords: COVID-19; Heparins; ROTEM; Thrombosis.

PubMed Disclaimer

Conflict of interest statement

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Renke H. Olie has received research support and honoraria from 10.13039/100004326Bayer, 10.13039/100004319Pfizer/BMS, Leo Pharma, Portola, and 10.13039/100004339Sanofi. Hugo ten Cate received funding for research from 10.13039/100004326Bayer and 10.13039/100004319Pfizer, is a stakeholder in Coagulation Profile, is a consultant for Alveron, and has served on advisory boards for 10.13039/100004326Bayer, 10.13039/100004319Pfizer, Daiichi, Leo, and Gilead. Yvonne Henkens has received ROTEM cartridges free of charge for previous research unrelated to the current manuscript. All others report no conflicts of interest.

Figures

Fig. 1
Fig. 1
Flowchart UFH = unfractionated heparin, LMWH = low molecular weight heparin, ROTEM = rotational thromboelastometry.

References

    1. Connors J.M., Levy J.H. Thromboinflammation and the hypercoagulability of COVID-19. J. Thromb. Haemostasis. 2020;18(7):1559–1561. - PMC - PubMed
    1. Ranucci M., Ballotta A., Di Dedda U., Baryshnikova E., Dei Poli M., Resta M., et al. The procoagulant pattern of patients with COVID-19 acute respiratory distress syndrome. J. Thromb. Haemostasis. 2020;18(7):1747–1751. - PMC - PubMed
    1. Hulshof A.M., Brüggemann R.A.G., Mulder M.M.G., van de Berg T.W., Sels J.E.M., Olie R.H., et al. Serial EXTEM, FIBTEM, and tPA rotational thromboelastometry observations in the Maastricht intensive care COVID cohort-persistence of hypercoagulability and hypofibrinolysis despite anticoagulation. Front Cardiovasc Med. 2021;8 - PMC - PubMed
    1. Cuker A., Tseng E.K., Nieuwlaat R., Angchaisuksiri P., Blair C., Dane K., et al. American Society of Hematology 2021 guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19. Blood Adv. 2021;5(3):872–888. - PMC - PubMed
    1. Streng A.S., Delnoij T.S.R., Mulder M.M.G., Sels J., Wetzels R.J.H., Verhezen P.W.M., et al. Monitoring of unfractionated heparin in severe COVID-19: an observational study of patients on CRRT and ECMO. TH Open. 2020;4(4):e365–e375. - PMC - PubMed