Pharmacogenetics and anticoagulant therapy: two cases of genetically determined response to warfarin.
Inter- and intra-individual variability of response to warfarin means that its anticoagulant effect must be monitored, given the risk of thromboembolic complications and bleeding. This variability is influenced by gender, age, body mass index, smoking, diet, comorbid conditions, drug interactions and genetic factors. Pharmacogenetics refers to the study of genetic background to predict drug response, effectiveness and risk of adverse effects in a given patient. The authors illustrate its relevance in two case reports. A 40-year-old woman admitted for massive pulmonary thromboembolism underwent anticoagulant and fibrinolytic therapy, following which warfarin was needed in unusually high doses to achieve effective anticoagulation. The genetic variants c.430CC and c.1075AA of the CYP2C9 gene were identified, predisposing to rapid warfarin metabolism, as well as the c.-1639GG variant of the VKORC1 gene, associated with low sensitivity to the drug. Together, these variants give high resistance to warfarin. In the second case, a 76-year-old man with permanent atrial fibrillation developed excessive prolongation of prothrombin time after being treated with 5 mg/day warfarin for 5 days. The genetic variants c.430CC and c.1075AC of the CYP2C9 gene and 1639AA of the VKORC1 gene were identified. Together, these polymorphisms confer high sensitivity to warfarin, necessitating smaller doses to maintain therapeutic anticoagulation levels. The authors review the relevance of the study of genetic polymorphisms related to anticoagulant therapy and discuss its potential usefulness in clinical practice.
Cortez-Dias
Nuno
N
Unidade de Tratamentos Intensivos Cardiológicos-Arsénio Cordeiro do Serviço de Cardiologia, Hospital de Santa Maria, Centro Hospitalar de Lisboa Norte, Lisboa, Portugal. cortezdias@yahoo.com
Correia
Maria José
MJ
Coutinho
Ana
A
Fernandes
Catarina
C
Diogo
A Nunes
AN
Lopes
Mário G
MG
D000328:Adult; D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D011655:Pulmonary Embolism / Q000188:drug therapy* / Q000235:genetics*; D014859:Warfarin / Q000627:therapeutic use*
D000925:Anticoagulants; D014859:Warfarin