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

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

doi:10.1055/s-0040-1719083

Renske H Olie, Hugo Ten Cate + Show 13 more

Open Access

https://doi.org/10.1055/s-0040-1719083

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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.

Highlights

In patients with severe cases of coronavirus disease 2019 (COVID-19) admitted to the intensive care unit (ICU), extracorporeal devices such as extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT) may be temporarily required to support organ function.[1,2,3] Use of ECMO and CRRT results in excessive stimulation of the coagulation system due to blood contact with a variety of nonphysiological surfaces, potentially leading to gradual or sudden thrombosis and the accumulation of thrombi throughout the extracorporeal system,[4] which can result in interruption of such supportive treatments
E366 Monitoring of Unfractionated Heparin in Severe COVID-19 Streng et al heparin therapeutic range (HTR) (0.3–0.7 IU/mL) and antithrombin III (ATIII) concentration was >70% for all patients; mean factor VIII (FVIII) and fibrinogen were 606% and 7.5 g/L, respectively. activated partial thromboplastin time (aPTT)-CS correlated with aPTT-STA (r2 1⁄4 0.68) with a bias of 39.3%
There was no general correlation between the aPTT-CS and ATIII, FVIII, fibrinogen, thrombocytes, C-reactive protein, or ferritin

Summary

Introduction

In patients with severe cases of coronavirus disease 2019 (COVID-19) admitted to the intensive care unit (ICU), extracorporeal devices such as extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT) may be temporarily required to support organ function.[1,2,3] Use of ECMO and CRRT results in excessive stimulation of the coagulation system due to blood contact with a variety of nonphysiological surfaces, potentially leading to gradual or sudden thrombosis and the accumulation of thrombi throughout the extracorporeal system,[4] which can result in interruption of such supportive treatments. Adequate anticoagulation is required during these procedures,[5,6] for which unfractionated heparin (UFH) is commonly used. The activated partial thromboplastin time (aPTT) reflects the intrinsic coagulation pathway and is the most commonly used test to monitor UFH.[9,10] Activated clotting time and anti-Xa activity tests are performed.[10] When using the anti-Xa test, practical guidelines suggest a heparin therapeutic range (HTR) of 0.3 to 0.7 IU/mL.[11,12,13] those same guidelines are less specific about which HTR to use when monitoring UFH with the aPTT. We utilize two different instruments for the aPTT: the Sysmex CS2100i (optical clot detection and the default instrument) and the Stago STA-R Max 2 (mechanical clot detection)

Methods

Results

Conclusion