@article{LindhoffLastBirschmannBidenharnetal.2022,
  author    = {Lindhoff-Last, Edelgard and Birschmann, Ingvild and Bidenharn, Antonia J. and Kuhn, Joachim and Lindau, Simone and Konstantinides, Stavros and Grottke, Oliver and Nowak-G{\"o}ttl, Ulrike and Lucks, Jessica and Zydek, Barbara and Heymann, Christian von and S{\"u}mnig, Ariane and Beyer-Westendorf, Jan and Schellong, Sebastian and Meybohm, Patrick and Greinacher, Andreas and Herrmann, Eva},
  title     = {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)},
  series = {Pharmaceuticals},
  volume    = {15},
  journal   = {Pharmaceuticals},
  number    = {11},
  issn      = {1424-8247},
  doi       = {10.3390/ph15111437},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-297226},
  year      = {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.},
  language  = {en}
}