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

Alexander S. Streng; Thijs S.R. Delnoij; Mark M.G. Mulder; Jan Willem E.M. Sels; Rick J.H. Wetzels; Paul W.M. Verhezen; Renske H. Olie; Jeroen P. Kooman; Sander M.J. van Kuijk; Lloyd Brandts; Hugo ten Cate; Roberto Lorusso; Iwan C.C. van der Horst; Bas C.T. van Bussel; Yvonne M.C. Henskens

doi:10.1055/s-0040-1719083

TH Open, Inhaltsverzeichnis

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^*

¹Central Diagnostic Laboratory, Maastricht University Medical Centre, Maastricht, the Netherlands

,

Thijs S.R. Delnoij^*

²Intensive Care Unit, Maastricht University Medical Centre, Maastricht, the Netherlands

³Cardiovascular Centre, Maastricht University Medical Centre, Maastricht, the Netherlands

,

Mark M.G. Mulder

²Intensive Care Unit, Maastricht University Medical Centre, Maastricht, the Netherlands

,

Jan Willem E.M. Sels

²Intensive Care Unit, Maastricht University Medical Centre, Maastricht, the Netherlands

³Cardiovascular Centre, Maastricht University Medical Centre, Maastricht, the Netherlands

,

Rick J.H. Wetzels

¹Central Diagnostic Laboratory, Maastricht University Medical Centre, Maastricht, the Netherlands

,

Paul W.M. Verhezen

¹Central Diagnostic Laboratory, Maastricht University Medical Centre, Maastricht, the Netherlands

,

Renske H. Olie

⁴Department of Vascular Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands

⁵Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands

,

Jeroen P. Kooman

⁶Department of Clinical Nephrology, Maastricht University Medical Centre, Maastricht, the Netherlands

,

Sander M.J. van Kuijk

⁷Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre, Maastricht, the Netherlands

⁸Care and Public Health Research Institute, Maastricht University Medical Centre, Maastricht, the Netherlands

,

Lloyd Brandts

⁷Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Centre, Maastricht, the Netherlands

,

Hugo ten Cate

⁴Department of Vascular Medicine, Maastricht University Medical Centre, Maastricht, the Netherlands

⁵Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands

,

Roberto Lorusso

⁵Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands

⁹Department of Cardiothoracic Surgery, Heart and Vascular Centre, Maastricht University Medical Centre, Maastricht, the Netherlands

,

Iwan C.C. van der Horst

²Intensive Care Unit, Maastricht University Medical Centre, Maastricht, the Netherlands

,

Bas C.T. van Bussel

²Intensive Care Unit, Maastricht University Medical Centre, Maastricht, the Netherlands

⁸Care and Public Health Research Institute, Maastricht University Medical Centre, Maastricht, the Netherlands

,

Yvonne M.C. Henskens

¹Central Diagnostic Laboratory, Maastricht University Medical Centre, Maastricht, the Netherlands

⁵Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, the Netherlands

› Institutsangaben

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

Volltext

Referenzen

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