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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)

Authors :
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 Meybohm
Andreas Greinacher
Eva Herrmann
Source :
Pharmaceuticals, Vol 15, Iss 11, p 1437 (2022)
Publication Year :
2022
Publisher :
MDPI AG, 2022.

Abstract

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.

Details

Language :
English
ISSN :
14248247
Volume :
15
Issue :
11
Database :
Directory of Open Access Journals
Journal :
Pharmaceuticals
Publication Type :
Academic Journal
Accession number :
edsdoj.3177b3688d844fa09c641747e9b9e68a
Document Type :
article
Full Text :
https://doi.org/10.3390/ph15111437