title: Monitoring of dabigatran anticoagulation and its reversal in vitro by thrombelastography.
abstract: BACKGROUND
  Dabigatran etexilate, a pro-drug of a direct thrombin inhibitor, was approved a few years ago for non-valvular atrial fibrillation and deep venous thrombosis. Rapid monitoring of the dabigatran level is essential in trauma and bleeding patients but the traditional plasma-based assays may not sufficiently display the effect. Furthermore, no antidote exists and reversal of the anticoagulant effect is impossible or difficult. The present study investigated the in vitro effect of dabigatran on whole blood thromboelastography (TEG) and its reversal by recombinant activated factor VII and prothrombin complex concentrate.
  
  
  METHODS
  Blood was collected from 10 healthy donors and spiked in vitro with therapeutic doses of dabigatran to a plasma concentration of 200 ng/ml, followed by therapeutic doses of recombinant activated factor VII (corresponding to 100 μg/kg) and prothrombin complex concentrate (corresponding to 50 IE/kg) and evaluated by TEG.
  
  
  RESULTS
  Compared to baseline, dabigatran changed all TEG parameters in a hypocoagulable direction corresponding to increased R time and time to maximum rate of thrombus generation, reduced angle, A5, A10, maximum amplitude and maximum rate of thrombin formation. Recombinant activated factor VII had a procoagulant effect on the majority of the investigated TEG parameters when added to dabigatran spiked samples. Prothrombin complex concentrate appeared not to have a procoagulant effect on TEG even when the heparin content in the formulation was neutralized by heparinase.
  
  
  CONCLUSIONS
  TEG displays the presence of dabigatran in whole blood in vitro and the anticoagulant effect of dabigatran is partly reversed by spiking with recombinant activated factor VII.
authors.affiliation: Section for Transfusion Medicine, Capital Region Blood Bank, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark. Electronic address: sacha@solbeck.dk.
authors.forename: Sacha
authors.initials: S
authors.lastname: Solbeck
authors.affiliation: Section for Transfusion Medicine, Capital Region Blood Bank, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
authors.forename: Martin A S
authors.initials: MA
authors.lastname: Meyer
authors.affiliation: Section for Transfusion Medicine, Capital Region Blood Bank, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
authors.forename: Pär I
authors.initials: PI
authors.lastname: Johansson
authors.affiliation: Section for Transfusion Medicine, Capital Region Blood Bank, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
authors.forename: Anna Sina P
authors.initials: AS
authors.lastname: Meyer
authors.affiliation: The Center for Translational Injury Research (CeTIR), University of Texas Health Science Center, Houston, TX, United States; The Department of Surgery, University of Texas Health Science Center, Houston, TX, United States.
authors.forename: Bryan A
authors.initials: BA
authors.lastname: Cotton
authors.affiliation: Section for Transfusion Medicine, Capital Region Blood Bank, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark; Department of Anaesthesiology, Centre of Head and Orthopaedics, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Jakob
authors.initials: J
authors.lastname: Stensballe
authors.affiliation: Skåne University Hospital, Lund, Skåne, Sweden.
authors.forename: Ulf
authors.initials: U
authors.lastname: Schött
authors.affiliation: Section for Transfusion Medicine, Capital Region Blood Bank, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
authors.forename: Sisse R
authors.initials: SR
authors.lastname: Ostrowski
mesh_terms: D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000097:blood* / Q000494:pharmacology*; D001562:Benzimidazoles / Q000097:blood* / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects / Q000502:physiology; D000069604:Dabigatran; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D013916:Thrombelastography / Q000379:methods*; D055815:Young Adult; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology
chemical_list: D000925:Anticoagulants; D001562:Benzimidazoles; D015091:beta-Alanine; D000069604:Dabigatran
keywords: Activated recombinant factor VII; Anticoagulation; Atrial fibrillation; Dabigatran; Prothrombin complex concentrate; Thromboelastography