Genetic Testing May Help Make Blood Thinner Safer

Warfarin (Coumadin, Jantoven) is often prescribed to prevent life-threatening blood clots in high-risk patients. However, a patient’s genes can influence how warfarin is processed in the body. Too little warfarin will not prevent blood clots while too much can trigger internal bleeding, the researchers explained.

Warfarin is “a widely used anticoagulant, but it causes more major adverse events than any other oral drug. Thousands of patients end up in the emergency department or hospital because of warfarin-induced bleeding. But we continue to prescribe it because it is highly effective, reversible and inexpensive,” said study first author Dr. Brian Gage. He is a professor of medicine at Washington University School of Medicine in St. Louis.

The researchers said they found that by looking for variants in three genes, it’s possible to make warfarin therapy safer.

Variants in one gene affect vitamin K recycling (vitamin K is needed for blood clotting). Variants in another gene affect warfarin sensitivity. And variants in the third gene affect warfarin metabolism in the liver and can cause an overdose if the dose is not adjusted quickly enough, the researchers said.

The study included about 1,600 people 65 and older at high risk for blood clots after undergoing hip or knee replacement surgery. They were randomly assigned to receive either warfarin dosing based on standard clinical factors such as age, height and weight. Or dosing based on those clinical factors plus variants in the three genes.



At least one adverse event (bleeding blood clots in the veins or warfarin overdoses) occurred in 15% of patients dosed in the traditional way and in 11% of patients whose dosing was guided by genetic testing – at 27% difference.

Along with the three variants analyzed in this study, there “are additional genetic variants that may help to guide warfarin dosing, especially among patients with African ancestry. In the future, we hope to quantify how these variants affect warfarin,” Gage said in a school news release.

“Although genetic testing is more expensive than clinical dosing, the cost is falling. In our study, we estimated that genetic testing costs less than $200 per person, which is less than one month of a newer anticoagulant,” Gage noted.

The study was published Sept. 26 in the Journal of the American Medical Association.

My Take:
Warfarin is rat poison. The therapeutic range and lethal dose are very close. Of all the drugs on the market, it is the one I hate the most.
This genetic testing will improve the safety of warfarin and the test has been fast tracked for public use. I had a patient last week taking warfarin that is scheduled for genetic testing this week.

More lives would be saved if they would limit warfarin to high-risk patients. Unfortunately, this drug is often prescribed for low-risk patients as well. It’s not only a dangerous drug, it’s too popular. The newer anticoagulants might be safer, but as mentioned, they are also very expensive.

The Bottom Line:
If you are on warfarin, please talk to your prescribing physician about eliminating the drug. If not, request the genetic testing to improve dosing.

Source: September 26, 2017 National Institutes of Health