title: Dabigatran and its reversal with recombinant factor VIIa and prothrombin complex concentrate: a Sonoclot in vitro study.
abstract: OBJECTIVE
  Dabigatran is a new oral direct thrombin inhibitor. No specific antidote exists in the event of hemorrhage, but prothrombin complex concentrate (PCC) and recombinant activated factor VII (rFVIIa) are suggested therapies. Sonoclot is a bedside viscoelastic instrument for monitoring the coagulation process in whole blood. The aim of this study was to investigate the effect of dabigatran and reversal with PCC and rFVIIa, as monitored by the Sonoclot.
  
  
  METHODS
  Citrated whole blood was drawn and mixed in vitro with dabigatran, dabigatran + PCC or dabigatran + rFVIIa and analyzed with three different Sonoclot cuvettes: Glassbead, kaolin and tissue factor (diluted) activated.
  
  
  RESULTS
  The Sonoclot detected in vitro-induced anticoagulation due to dabigatran with the glassbead- and kaolin-activated cuvettes. There was no reversing effect of PCC, probably due to the presence of heparin in the PCC we used. There was no certain reversing effect of rFVIIa.
  
  
  CONCLUSIONS
  The Sonoclot can detect the anticoagulant effect of dabigatran. Our results do not support efficient reversal of dabigatran with PCC and rFVIIa, or alternatively do not support the ability of Sonoclot to detect a reversing effect of the PCC and rFVIIa in our study. Clinical studies of dabigatran-treated patients with severe bleeding are called for, as well as the continued development of specific antidotes and monitoring techniques.
authors.affiliation: Section for Transfusion Medicine, Capital Region Blood Bank, Rigshospitalet, University of Copenhagen , Copenhagen , Denmark.
authors.forename: Sacha
authors.initials: S
authors.lastname: Sølbeck
authors.forename: Caroline U
authors.initials: CU
authors.lastname: Nilsson
authors.forename: Martin
authors.initials: M
authors.lastname: Engström
authors.forename: Sisse R
authors.initials: SR
authors.lastname: Ostrowski
authors.forename: Pär I
authors.initials: PI
authors.lastname: Johansson
mesh_terms: D000991:Antithrombins / Q000009:adverse effects / Q000494:pharmacology*; D001562:Benzimidazoles / Q000009:adverse effects / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects*; D001779:Blood Coagulation Factors / Q000494:pharmacology* / Q000627:therapeutic use; D000069604:Dabigatran; D064420:Drug-Related Side Effects and Adverse Reactions / Q000188:drug therapy; D015942:Factor VIIa / Q000494:pharmacology* / Q000627:therapeutic use; D006470:Hemorrhage / Q000188:drug therapy; D006801:Humans; D015091:beta-Alanine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000991:Antithrombins; D001562:Benzimidazoles; D001779:Blood Coagulation Factors; D015091:beta-Alanine; C025667:prothrombin complex concentrates; D015942:Factor VIIa; D000069604:Dabigatran
keywords: Antithrombins; blood coagulation factors; blood coagulation tests; factor VII; hemorrhage; thrombelastography