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CC BY 4.0 · TH Open 2020; 04(04): e365-e375
DOI: 10.1055/s-0040-1719083
Original Article

Monitoring of Unfractionated Heparin in Severe COVID-19: An Observational Study of Patients on CRRT and ECMO

Alexander S. Streng   *
1   Central Diagnostic Laboratory, Maastricht University Medical Centre, Maastricht, the Netherlands
,
Thijs S.R. Delnoij   *
2   Intensive Care Unit, Maastricht University Medical Centre, Maastricht, the Netherlands
3   Cardiovascular Centre, Maastricht University Medical Centre, Maastricht, the Netherlands
,
Mark M.G. Mulder
2   Intensive Care Unit, Maastricht University Medical Centre, Maastricht, the Netherlands
,
Jan Willem E.M. Sels
2   Intensive Care Unit, Maastricht University Medical Centre, Maastricht, the Netherlands
3   Cardiovascular Centre, Maastricht University Medical Centre, Maastricht, the Netherlands
,
Rick J.H. Wetzels
1   Central Diagnostic Laboratory, Maastricht University Medical Centre, Maastricht, the Netherlands
,
Paul W.M. Verhezen
1   Central Diagnostic Laboratory, Maastricht University Medical Centre, Maastricht, the Netherlands
,
Renske H. Olie
4   Department of Vascular Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands
5   Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands
,
Jeroen P. Kooman
6   Department of Clinical Nephrology, Maastricht University Medical Centre, Maastricht, the Netherlands
,
Sander M.J. van Kuijk
7   Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre, Maastricht, the Netherlands
8   Care and Public Health Research Institute, Maastricht University Medical Centre, Maastricht, the Netherlands
,
Lloyd Brandts
7   Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre, Maastricht, the Netherlands
,
Hugo ten Cate
4   Department of Vascular Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands
5   Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands
,
Roberto Lorusso
5   Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands
9   Department of Cardiothoracic Surgery, Heart and Vascular Centre, Maastricht University Medical Centre, Maastricht, the Netherlands
,
Iwan C.C. van der Horst
2   Intensive Care Unit, Maastricht University Medical Centre, Maastricht, the Netherlands
,
Bas C.T. van Bussel
2   Intensive Care Unit, Maastricht University Medical Centre, Maastricht, the Netherlands
8   Care and Public Health Research Institute, Maastricht University Medical Centre, Maastricht, the Netherlands
,
Yvonne M.C. Henskens
1   Central Diagnostic Laboratory, Maastricht University Medical Centre, Maastricht, the Netherlands
5   Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands
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Abstract

Objective Severe cases of coronavirus disease 2019 (COVID-19) can require continuous renal replacement therapy (CRRT) and/or extracorporeal membrane oxygenation (ECMO). Unfractionated heparin (UFH) to prevent circuit clotting is mandatory but monitoring is complicated by (pseudo)-heparin resistance. In this observational study, we compared two different activated partial thromboplastin time (aPTT) assays and a chromogenic anti-Xa assay in COVID-19 patients on CRRT or ECMO in relation to their UFH dosages and acute phase reactants.

Materials and Methods The aPTT (optical [aPTT-CS] and/or mechanical [aPTT-STA] clot detection methods were used), anti-Xa, factor VIII (FVIII), antithrombin III (ATIII), and fibrinogen were measured in 342 samples from 7 COVID-19 patients on CRRT or ECMO during their UFH treatment. Dosage of UFH was primarily based on the aPTT-CS with a heparin therapeutic range (HTR) of 50–80s. Associations between different variables were made using linear regression and Bland–Altman analysis.

Results Dosage of UFH was above 35,000IU/24 hours in all patients. aPTT-CS and aPTT-STA were predominantly within the HTR. Anti-Xa was predominantly above the HTR (0.3–0.7 IU/mL) and ATIII concentration was >70% for all patients; mean FVIII and fibrinogen were 606% and 7.5 g/L, respectively. aPTT-CS correlated with aPTT-STA (r 2 = 0.68) with a bias of 39.3%. Correlation between aPTT and anti-Xa was better for aPTT-CS (0.78 ≤ r 2 ≤ 0.94) than for aPTT-STA (0.34 ≤ r 2 ≤ 0.81). There was no general correlation between the aPTT-CS and ATIII, FVIII, fibrinogen, thrombocytes, C-reactive protein, or ferritin.

Conclusion All included COVID-19 patients on CRRT or ECMO conformed to the definition of heparin resistance. A patient-specific association was found between aPTT and anti-Xa. This association could not be explained by FVIII or fibrinogen.

Keywords

COVID-19 - heparin resistance - heparin therapeutic range - aPTT - anti-Xa

* Equal contribution.




Publication History

Received: 09 September 2020

Accepted: 25 September 2020

Article published online:
19 November 2020

© 2020. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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