RESUMO
AIMS: The study aims to evaluate the impact of genetic, demographic and clinical data on various measures of outcome of anticoagulation quality in patients. PATIENTS AND METHODS: The study consisted of 310 patients receiving long-term oral anticoagulation therapy in our hospital. Apart from demographic and clinical variables, 21 SNPs (in 7 genes) were analyzed and compared with the outcomes of anticoagulation therapy. Various outcomes that were measured are; supra therapeutic INRs (INR >3, >6), anticoagulation stabilization, time taken to stabilize and proportion of INRs within (2-3), above (>3) and below (<2) therapeutic range. RESULTS: Supra therapeutic INRs were influenced by CYP2C9*2, *3, CYP4F2 rs2108622, VKORC1-1639G>A, 1173C>T, rs55894764 along with concomitant drugs, smoking, body weight and height. Persistently fluctuating INRs/absolute instability correlated with VKORC1-1639G>A, gender, height and body mass index. The time taken to stabilize was associated with CYP4F2 rs2108622, CYP2C9*14, smoking, clinical indication and concomitant drugs. The overall distribution of INR was influenced by variants in CYP4F2 rs2108622, CYP2C9*3, rs9332230, VKORC1 1173C>T, -1639G>A, rs55894764, ABCB1 rs2032582, rs1128503, rs1045642 and F5 rs6025, age, smoking and concomitant drugs. CONCLUSIONS: Knowledge of factors influencing the quality of long term anticoagulation can help clinicians to customize therapy either by dose variation, therapy with alternate choice of drug, concurrent heparin therapy and/or frequent INR monitoring.
Assuntos
Anticoagulantes/farmacologia , Citocromo P-450 CYP2C9/genética , Sistema Enzimático do Citocromo P-450/genética , Fator V/genética , Polimorfismo de Nucleotídeo Único , Vitamina K Epóxido Redutases/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Adulto , Idoso , Família 4 do Citocromo P450 , Feminino , Humanos , Coeficiente Internacional Normatizado , Masculino , Pessoa de Meia-IdadeRESUMO
Levetiracetam is a commonly used broad-spectrum anticonvulsant efficacious in both partial and generalized seizures. It has an extremely favorable side effect profile with few drug-drug interactions, low potential for hematological and hepatic toxicity, and thus has rapidly become the preferred drug in patients with traumatic brain injuries who need seizure prophylaxis. We report, here, a patient who was started on levetiracetam for seizure prophylaxis after developing large bifrontal-parietal traumatic subdural hematomas (SDH) following a fall from a horse necessitating bifrontal craniotomies for evacuation. The patient developed an asymptomatic elevation of the liver enzymes. The liver enzymes trended back to normal after levetiracetam was stopped, and topiramate was initiated in its place.
