Public Defence: Nina Haagenrud Schultz Nina Haagenrud Schultz at Institute of Clinical medicine will be defending the thesis "Oral factor Xa inhibitors: Studies on reversal of their anticoagulant effect and on their influence on primary hemostasis, endothelial function and fibrinolysis" for the degree of PhD (Philosophiae Doctor).

Trial lecture - time and place

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Adjudication committee

  • First opponent: Professor Sam Schulman, McMaster University, Ontario, Canada
  • Second opponent: Senior Consultant Fariba Baghaei Borzabadi, Sahlgrenska University Hospital, Gothenburg, Sweden
  • Third member and chair of the evaluation committee: Professor Bjørn Bendz, Institute of Clinical Medicine, University of Oslo

Chair of defence

Professor II, Geir E. Tjønnfjord, Institute of Clinical Medicine, University of Oslo 

Principal Supervisor

Professor II Pål Andre Holme, Institute of Clinical Medicine, University of Oslo


Direct-acting oral anticoagulants (DOACs) were recently introduced for clinical use before a specific reversal strategy had been developed. In spite of their short half-life, a reversal strategy may be lifesaving in case of major bleeding or when urgent surgery is required. An antidote for activated factor X (FXa) inhibitors is not yet available in Norway.

We have performed in vitro-studies with potential reversal agents of the FXa inhibitors rivaroxaban and apixaban and a case series where the effect of apixaban was reversed with the activated prothrombin complex concentrate (aPCC) FEIBA® in three patients in need of urgent heart surgery. Furthermore, the effect of rivaroxaban other parts of hemostasis other than the coagulation system was investigated.

We found that aPCC, in a lower dose than recommended in current guidelines, was more effective in reversing the anticoagulation effect of both rivaroxaban and apixaban than recombinant FVIIa and four-factor prothrombin complex concentrate (PCC). aPCC 25-30 IU/kg also had a good hemostatic effect in two out of three apixaban-treated patients assessed both clinically, and by laboratory assays.

No influence of rivaroxaban on platelet aggregation, von Willebrand factor or markers of endothelial activation was found. However, after measurements of fibrinolytic markers, we detected a reduction of plasminogen activator inhibitor (PAI-1) in samples with peak concentrations of rivaroxaban.

In conclusion, aPCC may be a potential reversal agent of FXa inhibitors. Furthermore,

rivaroxaban may increase fibrinolytic activity by reducing the level of PAI-1.

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Published Oct. 25, 2019 12:35 PM - Last modified Nov. 7, 2019 2:03 PM