Doctors test genetic approach to blood thinner dosing

Genetic information could help doctors to determine the best dose of the blood thinner warfarin to prevent blood clots and serious bleeding, researchers say.

Warfarin, sold under the brand name Coumadin, is based on rat poison. Correct dosing is important, because too much can cause a patient to bleed to death, while too little can cause heart attacks or strokesfrom clotting.

'We're hoping that our research will help clinicians get it right on the first try.' Dr. Russ Altman

In Wednesday's online issue of the New England Journal of Medicine, researchers used clinical and genetic information from 4,043 subjects from many ethnic groups to create a computer algorithm or formula, aiming to predict how patients would respond to the drug.

"The algorithm accurately identified larger proportions of patients who required 21 mg of warfarin or less per week and of those who required 49 mg or more per week," study's authors wrote.

The amount of warfarin someone needs can vary by as much as 10-fold between individuals. Doctors currently start with a low dose and increase it gradually until blood tests show the dose is correct, but that process can take months.

"It appears that up to 46 per cent of people will require a warfarin dose that is significantly higher or lower than average," said the study's principal investigator, Dr. Russ Altman, a professor of bioengineering, genetics and medicine at Stanford University School of Medicine, noting that about 800,000 people are likely to be affected in the United States alone.

"We're hoping that our research will help clinicians get it right on the first try."

Non-average patients

The new approach is called pharmacogenetics using patient's genetic variations to predict their response to drugs.

Scientists know that two genes, called CYP2C9 and VKORC1, can vary slightly between individuals and influence the effectiveness of warfarin.

The algorithm flags the 10 to 30 per cent of people who are difficult to dose using standard methods, Altman said.

Next month, the U.S. National Institutes of Health is scheduled to launch a large randomized clinical trial of 1,200 participants of diverse backgrounds and ethnicities to confirm the results. Similar trials are planned in Europe.

"Pharmacogenetics has the potential to increase benefit and reduce harm in people whose drug responses are not 'average,'" the U.S. Food and Drug Administration's Dr. Janet Woodcock and Lawrence Lesko wrote in a journal commentary.

The researchers also hope to apply the approach to other drugs, since CYP2C9 affects the metabolism of at least 20 other commonly used medications, Altman said.