Assuntos
Coeficiente Internacional Normatizado/normas , Tromboplastina , Idoso , Idoso de 80 Anos ou mais , Monitoramento de Medicamentos , Feminino , Fármacos Hematológicos , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Femprocumona/farmacologia , Proteínas RecombinantesRESUMO
In 2006 a case report was published in this journal describing partial acenocoumarol- and phenprocoumon resistance in a 78-year-old man. A mutation in the VKORC1 gene was suggested to be the cause of the observed resistance. We examined the patient and found a new and hitherto unknown mutation in the VKORC1 gene which may well explain the observed resistance. The mutation concerns a polymorphism in exon 2 that predicts the substitution of tryptophan at position 59 of the VKOR protein by arginine, the p.Trp59Arg mutation. Meanwhile, we have detected the same p.Trp59Arg mutation in another patient with coumarin derivative resistance. The fact that this mutation did not occur in 100 individuals who responded well to coumarin derivatives, together with the knowledge that amino acid 59 is conserved among species, renders it likely that p.Trp59Arg was the cause of the partial acenocoumarol- and phenprocoumon resistance observed in these two patients.
Assuntos
Anticoagulantes/farmacologia , Cumarínicos/farmacologia , Resistência a Medicamentos/genética , Oxigenases de Função Mista/genética , Mutação de Sentido Incorreto , Humanos , Mutação de Sentido Incorreto/efeitos dos fármacos , Vitamina K/metabolismo , Vitamina K Epóxido RedutasesRESUMO
Treatment with coumarin derivatives is highly individualised due to high intra- and inter-individual variation in dose response and risks of severe bleeding or thromboembolic complications. Treatment focuses on reaching and maintaining a stable target international normalised ratio (INR). However, unexpected INRs that are not explained by noncompliance or vitamin K intake may occur. Here we describe seven cases of unexpected INRs, and provide clues that clarify the underlying mechanism.