tetano
Editor, Senior Moderator
TH Open
. 2020 Nov 19;4(4):e365-e375.
doi: 10.1055/s-0040-1719083. eCollection 2020 Oct.
Monitoring of Unfractionated Heparin in Severe COVID-19: An Observational Study of Patients on CRRT and ECMO
Alexander S Streng[SUP] 1 [/SUP], Thijs S R Delnoij[SUP] 2 3 [/SUP], Mark M G Mulder[SUP] 2 [/SUP], Jan Willem E M Sels[SUP] 2 3 [/SUP], Rick J H Wetzels[SUP] 1 [/SUP], Paul W M Verhezen[SUP] 1 [/SUP], Renske H Olie[SUP] 4 5 [/SUP], Jeroen P Kooman[SUP] 6 [/SUP], Sander M J van Kuijk[SUP] 7 8 [/SUP], Lloyd Brandts[SUP] 7 [/SUP], Hugo Ten Cate[SUP] 4 5 [/SUP], Roberto Lorusso[SUP] 5 9 [/SUP], Iwan C C van der Horst[SUP] 2 [/SUP], Bas C T van Bussel[SUP] 2 8 [/SUP], Yvonne M C Henskens[SUP] 1 5 [/SUP]
Affiliations
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 [SUP]2[/SUP] = 0.68) with a bias of 39.3%. Correlation between aPTT and anti-Xa was better for aPTT-CS (0.78 ≤ r [SUP]2[/SUP] ≤ 0.94) than for aPTT-STA (0.34 ≤ r [SUP]2[/SUP] ≤ 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; aPTT; anti-Xa; heparin resistance; heparin therapeutic range.
. 2020 Nov 19;4(4):e365-e375.
doi: 10.1055/s-0040-1719083. eCollection 2020 Oct.
Monitoring of Unfractionated Heparin in Severe COVID-19: An Observational Study of Patients on CRRT and ECMO
Alexander S Streng[SUP] 1 [/SUP], Thijs S R Delnoij[SUP] 2 3 [/SUP], Mark M G Mulder[SUP] 2 [/SUP], Jan Willem E M Sels[SUP] 2 3 [/SUP], Rick J H Wetzels[SUP] 1 [/SUP], Paul W M Verhezen[SUP] 1 [/SUP], Renske H Olie[SUP] 4 5 [/SUP], Jeroen P Kooman[SUP] 6 [/SUP], Sander M J van Kuijk[SUP] 7 8 [/SUP], Lloyd Brandts[SUP] 7 [/SUP], Hugo Ten Cate[SUP] 4 5 [/SUP], Roberto Lorusso[SUP] 5 9 [/SUP], Iwan C C van der Horst[SUP] 2 [/SUP], Bas C T van Bussel[SUP] 2 8 [/SUP], Yvonne M C Henskens[SUP] 1 5 [/SUP]
Affiliations
- PMID: 33235946
- PMCID: PMC7676995
- DOI: 10.1055/s-0040-1719083
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 [SUP]2[/SUP] = 0.68) with a bias of 39.3%. Correlation between aPTT and anti-Xa was better for aPTT-CS (0.78 ≤ r [SUP]2[/SUP] ≤ 0.94) than for aPTT-STA (0.34 ≤ r [SUP]2[/SUP] ≤ 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; aPTT; anti-Xa; heparin resistance; heparin therapeutic range.