TY - JOUR
AU - Kerstin Brehm, Oliver Krumnau, Claudia Heilmann, Friedhelm Beyersdorf
AB - OBJECTIVES Anticoagulation in patients with ventricular assist device (VAD) support is crucial and to date, no alternative to vitamin K antagonists (VKAs) can be safely used. Genetic variances of cytochrome p450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKORC) have been recently connected with variation of VKA maintenance as well as loading doses. In this retrospective study, we assessed the incidence of genetic variations and the influence of different genotypes of CYP2C9 and VKORC1 in VAD patients. METHODS A total of 161 patients received a VAD implant in our institution between January 2006 and July 2014. Of these, 63 consented to genetic analysis and completed an interview with standardized questions on phenprocoumon (PC) dosage, international normalized ratio and anticoagulation-related complications. Determination of VKORC (−1639 G > A; −1173 C > T) and of CYP2C9 (*2, 430 C > T; *3, 1075 A > C) polymorphisms was performed by polymerase chain reaction and restriction analysis. RESULTS The most common VKORC-1639 allele combination was wild-type GG (41%) followed by GA (32%) and AA (27%). Patients with VKORC1 polymorphisms AA and GA needed less PC in the maintenance phase of anticoagulation ( P < 0.001) compared with wild-type GG patients. In contrast, CYP2C9 polymorphisms showed no effect on PC doses. Similar findings were observed in the initiation phase of PC therapy. High complications rates under PC therapy were observed particularly at the beginning. CONCLUSIONS VKORC polymorphism affects PC dosage in the initiation as well as the maintenance phase. High rates of bleeding complications and thromboembolic events were found at the beginning of PC therapy in VAD patients. Therefore, a genotype-guided dosage algorithm might be useful in VAD patients. Key words CYP2C9 VKORC1 Phenprocoumon VAD Anticoagulation © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved. « Previous | Next Article » Table of Contents This Article Eur J Cardiothorac Surg (2016) 50 (2): 275-280. doi: 10.1093/ejcts/ezw060 First published online: March 16, 2016 » Abstract Free Full Text (HTML) Free Full Text (PDF) Free All Versions of this Article: ezw060v1 50/2/275 most recent Classifications TRANSPLANTATION AND MECHANICAL CIRCULATORY SUPPORT Services Article metrics Alert me when cited Alert me if corrected Find similar articles Similar articles in Web of Science Similar articles in PubMed Add to my archive Download citation Request Permissions Disclaimer Citing Articles Load citing article information Citing articles via CrossRef Citing articles via Scopus Citing articles via Web of Science Google Scholar Articles by Brehm, K. Articles by Beyersdorf, F. 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TI - Genetic variations of phenprocoumon metabolism in patients with ventricular assist devices
JF - European Journal of Cardio-Thoracic Surgery
DO - 10.1093/ejcts/ezw060
DA - 2016-08-01
UR - https://www.deepdyve.com/lp/oxford-university-press/genetic-variations-of-phenprocoumon-metabolism-in-patients-with-3oIOBf0C6a
SP - 275
EP - 280
VL - 50
IS - 2
DP - DeepDyve
ER -