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Pharmacokinetics of Phenprocoumon in Emergency Situations–Results of the Prospective Observational RADOA-Registry (Reversal Agent Use in Patients Treated with Direct Oral Anticoagulants or Vitamin K Antagonists Registry)

Affiliation
Coagulation Centre, Cardiology Angiology Centre Bethanien Hospital (CCB), 60389 Frankfurt, Germany
Lindhoff-Last, Edelgard;
Affiliation
Institute for Laboratory and Transfusion Medicine, Heart and Diabetes Centre, Ruhr University, 44789 Bochum, Germany
Birschmann, Ingvild;
ORCID
0000-0002-4410-6670
Affiliation
Institute of Biostatistics and Mathematical Modelling, Goethe University Frankfurt, 60590 Frankfurt, Germany
Bidenharn, Antonia J.;
Affiliation
Institute for Laboratory and Transfusion Medicine, Heart and Diabetes Centre, Ruhr University, 44789 Bochum, Germany
Kuhn, Joachim;
Affiliation
Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, 60590 Frankfurt, Germany
Lindau, Simone;
Affiliation
Center for Thrombosis and Hemostasis (CTH), University Medical Center, Johannes Gutenberg University, 55131 Mainz, Germany
Konstantinides, Stavros;
Affiliation
Department of Anaesthesiology, RWITH Aachen University Hospital, 52074 Aachen, Germany
Grottke, Oliver;
Affiliation
Institute of Clinical Chemistry, Thrombosis & Haemostasis Treatment Centre, University Hospital, 24105 Kiel-Lübeck, Germany
Nowak-Göttl, Ulrike;
Affiliation
Coagulation Research Centre, Cardiology Angiology Centre Bethanien Hospital (CCB), 60389 Frankfurt, Germany
Lucks, Jessica;
Affiliation
Coagulation Research Centre, Cardiology Angiology Centre Bethanien Hospital (CCB), 60389 Frankfurt, Germany
Zydek, Barbara;
Affiliation
Department of Anaesthesia, Intensive Care Medicine, Emergency Medicine and Pain Therapy, Vivantes Klinikum im Friedrichshain, 10249 Berlin, Germany
von Heymann, Christian;
Affiliation
Department of Immunology and Transfusion Medicine, Universitätsmedizin, 17475 Greifswald, Germany
Sümnig, Ariane;
Affiliation
Department of Medicine 1, Division of Thrombosis & Hemostasis, Dresden University Clinic, 01307 Dresden, Germany
Beyer-Westendorf, Jan;
Affiliation
Medical Department 2, Municipal Hospital, 01067 Dresden, Germany
Schellong, Sebastian;
ORCID
0000-0002-2666-8696
Affiliation
Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, 60590 Frankfurt, Germany
Meybohm, Patrick;
ORCID
0000-0001-8343-7336
Affiliation
Department of Immunology and Transfusion Medicine, Universitätsmedizin, 17475 Greifswald, Germany
Greinacher, Andreas;
ORCID
0000-0002-0662-6675
Affiliation
Institute of Biostatistics and Mathematical Modelling, Goethe University Frankfurt, 60590 Frankfurt, Germany
Herrmann, Eva

Background: Phenprocoumon has been used as an oral anticoagulant in patients with thromboembolic disease for more than 40 years. So far its pharmacokinetics have not been analyzed in emergency situations. Methods: Phenprocoumon-treated patients with major bleeding or urgent surgery were included in a prospective, observational registry. Phenprocoumon drug concentrations were analyzed in samples, collected as part of routine care using ultraperformance liquid chromatography tandem mass spectrometry. Moreover, anticoagulant intensity and drug half-life (t1/2) were calculated. Results: 115 patients were included. Phenprocoumon levels declined over time with a half-life of 5.27 and 5.29 days in patients with major bleedings ( n = 82) and with urgent surgery ( n = 33). Baseline phenprocoumon levels were 2.2 times higher in the bleeding group compared to the surgery group (1.92 vs. 0.87 ng/mL, p < 0.0001). International normalized ratio (INR) values decreased rapidly during the first 24 h. In 27.6% of patients a rebound of INR (recurrent increase > 1.5) was observed which was associated with significantly increased bleeding rates (22% vs. 4.2% in patients with or without INR rebound, p = 0.012). Conclusions: In emergency situations, the long half-life of phenprocoumon may cause INR rebound and associated recurrent bleedings. Optimal management may need to include repeated vitamin K supplementation over days.

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