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)
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- 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 drugBackground: 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.…
Autor(en): | Edelgard Lindhoff-Last, Ingvild Birschmann, Antonia J. Bidenharn, Joachim Kuhn, Simone Lindau, Stavros Konstantinides, Oliver Grottke, Ulrike Nowak-Göttl, Jessica Lucks, Barbara Zydek, Christian von Heymann, Ariane Sümnig, Jan Beyer-Westendorf, Sebastian Schellong, Patrick MeybohmORCiD, Andreas Greinacher, Eva Herrmann |
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URN: | urn:nbn:de:bvb:20-opus-297226 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Medizinische Fakultät / Klinik und Poliklinik für Anästhesiologie (ab 2004) |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | Pharmaceuticals |
ISSN: | 1424-8247 |
Erscheinungsjahr: | 2022 |
Band / Jahrgang: | 15 |
Heft / Ausgabe: | 11 |
Aufsatznummer: | 1437 |
Originalveröffentlichung / Quelle: | Pharmaceuticals (2022) 15:11, 1437. https://doi.org/10.3390/ph15111437 |
DOI: | https://doi.org/10.3390/ph15111437 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Freie Schlagwort(e): | INR rebound; emergency; major bleeding; pharmacokinetics; phenprocoumon; urgent surgery |
Datum der Freischaltung: | 16.11.2023 |
Datum der Erstveröffentlichung: | 19.11.2022 |
Lizenz (Deutsch): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |