Study leads to safer use of Warfarin

The blood-thinning drug Warfarin tops the list of adverse drug side-effects but new research has revealed a safer approach.

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By  Stuart Qualtrough Published  May 17, 2005

The blood-thinning drug Warfarin tops the list of adverse drug side-effects but new research has revealed a safer approach. The pharmacogenetic study at Uppsala University in Sweden has found it is possible to predict patient sensitivity to the life-saving drug through genetic profiling. Warfarin is used to prevent blood clots but patient reaction varies enormously and can lead to over-dosage and in certain cases even fatal bleeding. In Sweden since the 1960s more fatal side-effects have been reported from Warfarin than for any other drug. Of the 118 deaths reported in connection with drug treatment in Sweden last year, nearly half involved bleeding from Warfarin. There is still no good alternative to Warfarin in cases of blood clots or heart or valve diseases. All patients receive the same dose the first few days, then the dosage is determined by a test of the capacity of the blood to coagulate. The differences are great in how much Warfarin patients need to attain an effect. One patient can require 20 times the dose needed by another patient. The findings show that hereditary variations in two genes, together with the patient’s age, weight, disease, and other medicines, explain nearly 60 percent of the variations in dosage. One of the genes is called the vitamin-K-reductase gene and was discovered by two US research teams last year. The other gene is the gene for the enzyme cytochrome P450 2C9, which governs the degradation of Warfarin and has long been known. “We want to develop clinical analyses that can predict what dosage of Warfarin a patient should have from the moment the drug is prescribed. If we can create such analyses, then we can reduce the risk of early bleeding. With the newly discovered gene and our findings, we are one step closer to a solution,” said lead researcher Mia Wadelius.

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