@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}
}
@article{JustSchollBoehmeetal.2021,
  author    = {Just, Katja S. and Scholl, Catharina and Boehme, Miriam and Kastenm{\"u}ller, Kathrin and Just, Johannes M. and Bleckwenn, Markus and Holdenrieder, Stefan and Meier, Florian and Weckbecker, Klaus and Stingl, Julia C.},
  title     = {Individualized versus standardized risk assessment in patients at high risk for adverse drug reactions (the IDrug randomized controlled trial) - never change a running system?},
  series = {Pharmaceuticals},
  volume    = {14},
  journal   = {Pharmaceuticals},
  number    = {10},
  issn      = {1424-8247},
  doi       = {10.3390/ph14101056},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-248557},
  year      = {2021},
  abstract  = {The aim of this study was to compare effects of an individualized with a standardized risk assessment for adverse drug reactions to improve drug treatment with antithrombotic drugs in older adults. A randomized controlled trial was conducted in general practitioner (GP) offices. Patients aged 60 years and older, multi-morbid, taking antithrombotic drugs and at least one additional drug continuously were randomized to individualized and standardized risk assessment groups. Patients were followed up for nine months. A composite endpoint defined as at least one bleeding, thromboembolic event or death reported via a trigger list was used. Odds ratios (OR) and 95\% confidence intervals (CI) were calculated. In total, N = 340 patients were enrolled from 43 GP offices. Patients in the individualized risk assessment group met the composite endpoint more often than in the standardized group (OR 1.63 [95\%CI 1.02-2.63]) with multiple adjustments. The OR was higher in patients on phenprocoumon treatment (OR 1.99 [95\%CI 1.05-3.76]), and not significant on DOAC treatment (OR 1.52 [95\%CI 0.63-3.69]). Pharmacogenenetic variants of CYP2C9, 2C19 and VKORC1 were not observed to be associated with the composite endpoint. The results of this study may indicate that the time point for implementing individualized risk assessments is of importance.},
  language  = {en}
}