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

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 thromboela...

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Published in:	Thrombosis update Vol. 12; p. 100140
Main Authors:	Schultinge, Lejan, Hulshof, Anne-Marije, van Neerven, Danihel, Mulder, Mark M.G., Sels, Jan-Willem E.M., Hulsewe, Hendrina P.M.G., Kuiper, Gehardus J.A.J.M., Olie, Renske H., ten Cate, Hugo, van der Horst, Iwan C.C., van Bussel, Bas C.T., Henskens, Yvonne M.C.
Format:	Journal Article
Language:	English
Published:	England Elsevier Ltd 01-08-2023 Published by Elsevier Ltd Elsevier
Subjects:	COVID-19 Heparins ROTEM Thrombosis COVID-19 Thrombosis ROTEM Heparins
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Summary:	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. To evaluate the ROTEM INTEM/HEPTEM ratios in mechanically ventilated COVID-19 patients treated with UFH and therapeutic LMWH. 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. 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. 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. •A more in vivo representation of the UFH effect using the INTEM/HEPTEM CT ratio compared to the anti-Xa assay is suggested.•The whole-blood ROTEM assay may prove to be superior compared to the platelet poor plasma based aPTT in future research.•The INTEM/HEPTEM CT ratio appears promising to guide anticoagulant therapy in ICU patients on UFH.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Both authors contributed equally to this paper.
ISSN:	2666-5727 2666-5727
DOI:	10.1016/j.tru.2023.100140