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

Lejan Schultinge; Anne-Marije Hulshof; Danihel van Neerven; Mark M G Mulder; Jan-Willem E M Sels; Hendrina P M G Hulsewe; Gerardus J A J M Kuiper; Renske H Olie; Hugo Ten Cate; Iwan C C van der Horst; Bas C T van Bussel; Yvonne M C Henskens

doi:10.1016/j.tru.2023.100140

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

Thromb Update. 2023 Aug:12:100140. doi: 10.1016/j.tru.2023.100140. Epub 2023 Jun 7.

Authors

Lejan Schultinge^{1

2}, Anne-Marije Hulshof^{3

4}, Danihel van Neerven^{1

5}, Mark M G Mulder^{1

5}, Jan-Willem E M Sels^{1

4}, Hendrina P M G Hulsewe¹, Gerardus J A J M Kuiper⁵, Renske H Olie^{4

6

7}, Hugo Ten Cate^{4

6

7}, Iwan C C van der Horst^{1

4}, Bas C T van Bussel^{1

4

8}, Yvonne M C Henskens^{3

4}

Affiliations

¹ Department of Intensive Care Medicine, Maastricht University Medical Centre+, Maastricht, the Netherlands.
² Department of Intensive Care Medicine, Laurentius Hospital Roermond, the Netherlands.
³ Central Diagnostic Laboratory, Maastricht University Medical Centre+, Maastricht, the Netherlands.
⁴ Cardiovascular Research Institute Maastricht, Maastricht University+, Maastricht, the Netherlands.
⁵ Department of Anaesthesiology and Pain Treatment Maastricht University Medical Centre+, Maastricht, the Netherlands.
⁶ Department of Internal Medicine, Maastricht University Medical Centre+, Maastricht, the Netherlands.
⁷ Thrombosis Expert Centre Maastricht, Maastricht University Medical Centre+, Maastricht, the Netherlands.
⁸ Care and Public Health Research Institute, Maastricht University Medical Centre+, Maastricht, the Netherlands.

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.