title: Whole blood coagulation assays ROTEM and T-TAS to monitor dabigatran treatment.
abstract: BACKGROUND
  A rapid and reliable assessment of the dabigatran effect is desirable in dabigatran treated patients with uncontrolled bleeding or before acute surgery.
  
  
  OBJECTIVE
  To evaluate how the viscoelastic point-of-care test Rotational thromboelastometry (ROTEM) and Total Thrombus-formation system (T-TAS), which studies thrombus formation under flowing conditions, correlate with dabigatran concentrations in patients with atrial fibrillation (AF).
  
  
  METHODS
  ROTEM using the reagents In-tem, Ex-tem, Fib-tem or low tissue factor concentration (TF), and T-TAS with the AR-chip (shear rate 600s-1, representing flow in large arteries) were investigated in whole blood samples. Plasma concentrations were determined by mass spectrometry (LC-MS/MS) at trough and post-dose in 30 patients on dabigatran 150mg BID.
  
  
  RESULTS
  Median plasma dabigatran concentrations at trough were 86ng/mL (29-150) and post-dose (2.8h after ingestion) 175ng/mL (67-490). The ROTEM clotting time (CT) correlated strongly with dabigatran concentrations when activated with the reagents Ex-tem (r=0.92, p<0.01) and Fib-tem (r=0.93, p<0.01), while with In-tem and low TF the correlation was weaker (r=0.72 and r=0.36, p<0.01). There were significant but weaker correlations also between dabigatran concentrations and T-TAS variables (r-values 0.39-0.41, p<0.01), aPTT (r=0.70, p<0.01) and PT-INR (r=0.43, p<0.01) respectively.
  
  
  CONCLUSIONS
  ROTEM Ex-tem and Fib-tem CT shows a strong correlation with dabigatran concentrations in real-life AF-patients, and results are obtained within minutes. This could make ROTEM useful in acute situations. T-TAS detect differences in hemostasis caused by dabigatran, but the relationships to plasma concentrations of dabigatran are weaker than for ROTEM CT with the settings used in this study.
authors.affiliation: Department of Clinical Sciences, Danderyd Hospital, Division of Cardiovascular Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Viktor
authors.initials: V
authors.lastname: Taune
authors.affiliation: Department of Clinical Sciences, Danderyd Hospital, Division of Cardiovascular Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Håkan
authors.initials: H
authors.lastname: Wallén
authors.affiliation: Department of Medicine, Division of Hematology, Coagulation Unit, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Ågren
authors.affiliation: Division of Clinical Immunology and Transfusion Medicine, Karolinska University, Stockholm and Department of Laboratory Medicine, Karolinska Institutet, Sweden.
authors.forename: Gunilla
authors.initials: G
authors.lastname: Gryfelt
authors.affiliation: Department of Clinical Sciences, Danderyd Hospital, Division of Cardiovascular Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Carolina
authors.initials: C
authors.lastname: Sjövik
authors.affiliation: Department of Clinical Sciences, Danderyd Hospital, Division of Cardiovascular Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Wintler
authors.affiliation: Department of Medicine Solna, Karolinska Institutet & Clinical Pharmacology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Rickard E
authors.initials: RE
authors.lastname: Malmström
authors.affiliation: Division of Clinical Immunology and Transfusion Medicine, Karolinska University, Stockholm and Department of Laboratory Medicine, Karolinska Institutet, Sweden.
authors.forename: Agneta
authors.initials: A
authors.lastname: Wikman
authors.affiliation: Department of Clinical Sciences, Danderyd Hospital, Division of Cardiovascular Medicine, Karolinska Institutet, Stockholm, Sweden; Department of Medicine Solna, Karolinska Institutet & Clinical Pharmacology, Karolinska University Hospital, Stockholm, Sweden. Electronic address: mika.skeppholm@sll.se.
authors.forename: Mika
authors.initials: M
authors.lastname: Skeppholm
mesh_terms: D000368:Aged; D000991:Antithrombins / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000097:blood / Q000188:drug therapy*; D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests / Q000379:methods*; D000069604:Dabigatran / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019095:Point-of-Care Systems; D013916:Thrombelastography / Q000379:methods; D014914:Whole Blood Coagulation Time / Q000379:methods
chemical_list: D000991:Antithrombins; D000069604:Dabigatran
keywords: Atrial fibrillation; Dabigatran; Drug monitoring; Flow chamber system; Thromboelastography