Back to Search
Start Over
Mechanical heart valve recipients: anticoagulation in patients with genetic variations of phenprocoumon metabolism.
- Source :
-
European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery [Eur J Cardiothorac Surg] 2013 Aug; Vol. 44 (2), pp. 309-14; discussion 314-5. Date of Electronic Publication: 2013 Feb 19. - Publication Year :
- 2013
-
Abstract
- Objectives: Oral anticoagulation in mechanical heart valve recipients remains crucial, and vitamin K antagonists (VKA) are still the gold standard. Polymorphisms of vitamin K epoxide oxidase reductase (VKORC) and cytochrome p450 (CYP2C9) were recently found to influence VKA metabolism. We retrospectively investigated the prevalence of these genotypes and associated anticoagulation-related complications in our patients.<br />Methods: Between August 1998 and August 2008, 563 patients received mechanical heart valve replacement in our institution. Of these, 179 completed a questionnaire on anticoagulation-related complications and consented to genetic analysis. We analysed polymorphisms of VKORC (-1639 G>A; 1173 C>T) and of CYP2C9 (*2, 144 C>T; *3, 359 A>C) by PCR and restriction analysis.<br />Results: For VKORC-1639/1173 alleles, there were 62 (35%) patients with the combination GG/CC, 91 (51%) with GA/CT, 25 (14%) with AA/TT and 1 (1%) with AA/CT. Phenprocoumon (PC) dosage was related to VKORC polymorphism (P < 0.001) with lower doses required for AA/TT patients. Overall, there were 27 severe bleedings and 11 thromboembolic events. For GG/CC, the incidence of major bleeding events and thromboembolic events was 13 and 6%, respectively, and for AA/TT, it was 27 and 12%, respectively. Variation in international normalized ratio (INR) >1.5 was associated with severe bleeding complications (P = 0.025) and GA/CT patients were predisposed to INR variations >1.5 (P = 0.028). No influence of CYP2C9 polymorphism on PC dosage and anticoagulation-related complications was found.<br />Conclusions: VKORC polymorphism affects PC dosage and anticoagulation-related complication rates in mechanical heart valve recipients. Genotyping may help to identify patients at particular risk of anticoagulation-related complications.
- Subjects :
- Adult
Aged
Aged, 80 and over
Anticoagulants administration & dosage
Anticoagulants pharmacokinetics
Aryl Hydrocarbon Hydroxylases metabolism
Cytochrome P-450 CYP2C9
Female
Heart Valve Prosthesis
Hemorrhage genetics
Hemorrhage prevention & control
Humans
Male
Middle Aged
Odds Ratio
Phenprocoumon administration & dosage
Phenprocoumon pharmacokinetics
Polymorphism, Single Nucleotide
Postoperative Complications enzymology
Postoperative Complications genetics
Postoperative Complications prevention & control
Retrospective Studies
Thromboembolism drug therapy
Thromboembolism genetics
Thromboembolism prevention & control
Vitamin K Epoxide Reductases metabolism
Anticoagulants adverse effects
Aryl Hydrocarbon Hydroxylases genetics
Heart Valve Prosthesis Implantation methods
Hemorrhage enzymology
Phenprocoumon adverse effects
Thromboembolism enzymology
Vitamin K Epoxide Reductases genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1873-734X
- Volume :
- 44
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery
- Publication Type :
- Academic Journal
- Accession number :
- 23423913
- Full Text :
- https://doi.org/10.1093/ejcts/ezt002