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.

Acquired left ventricular-to-right atrial shunt (Gerbode defect) due to infective endocarditis.

Left ventricular-to-right atrial communications are a rare type of ventricular septal defect, known as the Gerbode defect. They are usually congenital, but rare cases have been described secondary to bacterial endocarditis. The authors present a rare case of Gerbode defect and severe pericardial effusion secondary to Staphylococcus aureus endocarditis, in a patient with alcoholic liver cirrhosis.

Avaliaçäo do desempenho ventricular no infarto agudo do miocárdio: I. Consideraçöes gerais / Evaluation of ventricular performance in acute myocardial infarction: I. General considerations

A disfunçäo do ventrículo esquerdo (VE) constitui a principal causa de morte dos doentes com infarto agudo do miocárdio (IAM) que säo internados em Unidades de Tratamento Intensivo de Coronários. Deste modo, compreende-se que a avaliaçäo do desempenho do VE tenha uma importância relevante na escolha da terapêutica a instituir, na apreciaçäo de sua eficácia e no prognóstico dos doentes com IAM. Na primeira seçäo deste Simpósio, analisa-se a fisiopatologia da disfunçäo do VE no IAM; na segunda, referem-se diversos indicadores clínicos do desempenho ventricular no IAM, nomeadamente as classes de Killip e o índice de Norris; na terceira, baseado num estudo efetuado em 250 doentes, valoriza-se a contribuiçäo do exame hemodinâmico com o cateter de Swan-Ganz para a avaliaçäo da funçäo cardíaca e para o prognóstico dos doentes com IAM; na quarta, decrevem-se os critérios hemodinâmicos que permitem o diagnóstico de infarto do ventrículo direito; na quinta, fundamentado num estudo que abrangeu 107 doentes, referem-se diversos índices fonomecanocardiográficos do desempenho do VE no IAM, designadamente: amplitude da onda a e morfologia do apexocardiograma; intervalos de tempo sistólico e diastólicos