Extreme sensitivity to acenocoumarol therapy in patient with both VKORC.-1639 A/A and CYP2C9*1/*3 genotypes
Samo za registrovane korisnike
2011
Članak u časopisu (Objavljena verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
The initiation phase of vitamin K antagonist (VKA) is a challenging and demanding process that can result in adverse event such as bleeding. Dosing is influenced by a variety of acquired factors, while another factor that is associated with the optimal dose is the presence of certain genetic variants. We describe a 73 years old male who required extremely low dose of acenocoumarol (0.33 mg/day) to reach the target INR of 2-2.5. During initiation of VKA he started with usually recommended doses of acenocoumarol: 4 mg/day for the first 2 days and 3 mg/day during next 2 days. On fifth day of initiation, massive haematuria occurred and INR level of 10.5 was recorded. Patient was transfused with three doses of fresh frozen plasma in order to stop the bleeding. Acenocoumarol dose was gradually reduced after every INR laboratory monitoring and finally a dose of 0.33 mg/day was required for maintain stable anticoagulation. The genotyping results performed after introducing of VKA showed the pa...tient was homozygous for vitamin K epoxide reductase (VKORC1) c.-1639 G gt A, and heterozygous for cytochrome P450 2C9 (CYP2C9)*3 which pointed to extreme sensitivity to acenocoumarol. Our case supports the need for prospective genotyping of CYP2C9 and VKORC1 prior to initiation of VKA where pharmacogenetics, as a good predictor of extreme sensitivity to VKA, could help to tailor optimal VKA dose.
Ključne reči:
VKORC1 / Pharmacogenetics / Overanticoagulation / CYP2C9*3 / AcenocoumarolIzvor:
Journal of Thrombosis and Thrombolysis, 2011, 32, 3, 368-371Izdavač:
- Springer, Dordrecht
Finansiranje / projekti:
- Kompleksne bolesti kao model sistem za proučavanje modulacije fenotipa-strukturna i funkcionalna analiza molekularnih biomarkera (RS-MESTD-Basic Research (BR or ON)-173008)
DOI: 10.1007/s11239-011-0601-x
ISSN: 0929-5305
PubMed: 21638223
WoS: 000294824100014
Scopus: 2-s2.0-82955237278
Institucija/grupa
Institut za molekularnu genetiku i genetičko inženjerstvoTY - JOUR AU - Kovač, Mirjana AU - Rakićević, Ljiljana AU - Radojković, Dragica PY - 2011 UR - https://imagine.imgge.bg.ac.rs/handle/123456789/498 AB - The initiation phase of vitamin K antagonist (VKA) is a challenging and demanding process that can result in adverse event such as bleeding. Dosing is influenced by a variety of acquired factors, while another factor that is associated with the optimal dose is the presence of certain genetic variants. We describe a 73 years old male who required extremely low dose of acenocoumarol (0.33 mg/day) to reach the target INR of 2-2.5. During initiation of VKA he started with usually recommended doses of acenocoumarol: 4 mg/day for the first 2 days and 3 mg/day during next 2 days. On fifth day of initiation, massive haematuria occurred and INR level of 10.5 was recorded. Patient was transfused with three doses of fresh frozen plasma in order to stop the bleeding. Acenocoumarol dose was gradually reduced after every INR laboratory monitoring and finally a dose of 0.33 mg/day was required for maintain stable anticoagulation. The genotyping results performed after introducing of VKA showed the patient was homozygous for vitamin K epoxide reductase (VKORC1) c.-1639 G gt A, and heterozygous for cytochrome P450 2C9 (CYP2C9)*3 which pointed to extreme sensitivity to acenocoumarol. Our case supports the need for prospective genotyping of CYP2C9 and VKORC1 prior to initiation of VKA where pharmacogenetics, as a good predictor of extreme sensitivity to VKA, could help to tailor optimal VKA dose. PB - Springer, Dordrecht T2 - Journal of Thrombosis and Thrombolysis T1 - Extreme sensitivity to acenocoumarol therapy in patient with both VKORC.-1639 A/A and CYP2C9*1/*3 genotypes EP - 371 IS - 3 SP - 368 VL - 32 DO - 10.1007/s11239-011-0601-x ER -
@article{ author = "Kovač, Mirjana and Rakićević, Ljiljana and Radojković, Dragica ", year = "2011", abstract = "The initiation phase of vitamin K antagonist (VKA) is a challenging and demanding process that can result in adverse event such as bleeding. Dosing is influenced by a variety of acquired factors, while another factor that is associated with the optimal dose is the presence of certain genetic variants. We describe a 73 years old male who required extremely low dose of acenocoumarol (0.33 mg/day) to reach the target INR of 2-2.5. During initiation of VKA he started with usually recommended doses of acenocoumarol: 4 mg/day for the first 2 days and 3 mg/day during next 2 days. On fifth day of initiation, massive haematuria occurred and INR level of 10.5 was recorded. Patient was transfused with three doses of fresh frozen plasma in order to stop the bleeding. Acenocoumarol dose was gradually reduced after every INR laboratory monitoring and finally a dose of 0.33 mg/day was required for maintain stable anticoagulation. The genotyping results performed after introducing of VKA showed the patient was homozygous for vitamin K epoxide reductase (VKORC1) c.-1639 G gt A, and heterozygous for cytochrome P450 2C9 (CYP2C9)*3 which pointed to extreme sensitivity to acenocoumarol. Our case supports the need for prospective genotyping of CYP2C9 and VKORC1 prior to initiation of VKA where pharmacogenetics, as a good predictor of extreme sensitivity to VKA, could help to tailor optimal VKA dose.", publisher = "Springer, Dordrecht", journal = "Journal of Thrombosis and Thrombolysis", title = "Extreme sensitivity to acenocoumarol therapy in patient with both VKORC.-1639 A/A and CYP2C9*1/*3 genotypes", pages = "371-368", number = "3", volume = "32", doi = "10.1007/s11239-011-0601-x" }
Kovač, M., Rakićević, L.,& Radojković, D.. (2011). Extreme sensitivity to acenocoumarol therapy in patient with both VKORC.-1639 A/A and CYP2C9*1/*3 genotypes. in Journal of Thrombosis and Thrombolysis Springer, Dordrecht., 32(3), 368-371. https://doi.org/10.1007/s11239-011-0601-x
Kovač M, Rakićević L, Radojković D. Extreme sensitivity to acenocoumarol therapy in patient with both VKORC.-1639 A/A and CYP2C9*1/*3 genotypes. in Journal of Thrombosis and Thrombolysis. 2011;32(3):368-371. doi:10.1007/s11239-011-0601-x .
Kovač, Mirjana, Rakićević, Ljiljana, Radojković, Dragica , "Extreme sensitivity to acenocoumarol therapy in patient with both VKORC.-1639 A/A and CYP2C9*1/*3 genotypes" in Journal of Thrombosis and Thrombolysis, 32, no. 3 (2011):368-371, https://doi.org/10.1007/s11239-011-0601-x . .