TY  - JOUR
A1  - Lindhoff-Last, Edelgard
A1  - Birschmann, Ingvild
A1  - Bidenharn, Antonia J.
A1  - Kuhn, Joachim
A1  - Lindau, Simone
A1  - Konstantinides, Stavros
A1  - Grottke, Oliver
A1  - Nowak-Göttl, Ulrike
A1  - Lucks, Jessica
A1  - Zydek, Barbara
A1  - Heymann, Christian von
A1  - Sümnig, Ariane
A1  - Beyer-Westendorf, Jan
A1  - Schellong, Sebastian
A1  - Meybohm, Patrick
A1  - Greinacher, Andreas
A1  - Herrmann, Eva
T1  - 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)
JF  - Pharmaceuticals
N2  - 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.
KW  - phenprocoumon
KW  - pharmacokinetics
KW  - emergency
KW  - major bleeding
KW  - urgent surgery
KW  - INR rebound
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-297226
SN  - 1424-8247
VL  - 15
IS  - 11
ER  -