Doctors prescribing Warfarin, a blood-thinning medication, will now be able to use genetic testing as a means of estimating the initial dosage size for their patients.
Data collected from 350 patients at Shands Hospital at UF and the Malcolm Randall VA Medical Center were combined with other international studies to show that a person's genes play a role in how the drug will affect their blood flow.
Warfarin is an anti-coagulant, also known as a blood thinner, which helps to prevent clot formation in the blood and is given to those who are at risk for blood clots. Warfarin works by inhibiting Vitamin K-dependent factors in the body, which contains proteins that deal with blood clotting.
According to Julie Johnson, director for UF's Center for Pharmacogenomics, about two million people in the US are currently taking Warfarin.
"Figuring out the right dose for the right person can be really tricky," she said. "The dose required can range from 1 milligram per day to 10 or 15 milligrams per day."
Patients are normally started off with a 5 milligram per day dose, which is then adjusted after seeing how the body and blood flow reacts to the medicine.
However, problems arise when patients are given too much or too little of the medicine. If a patient is given too much, they have a period of increased risk of fatal bleeding. But, if they are not given enough of it, they have an increased risk of clot formation, which can lead to a stroke.
"Warfarin is a difficult drug, although it's used in lots of patients," said Dr. Marc Zumberg, clinical assistant professor of medicine in the division of Hematology and Oncology at UF's College of Medicine, who was not involved in the study. "The dose is dependent on a lot of things such as diet and use of different medications."
For these reasons, Zumberg said patients' blood levels often fluctuate, causing dosage amount to change as well.
We have to follow their levels very closely," he said.
The study showed variations of two genes could control how much of an initial dosage a patient would need, thus eliminating most of the guesswork done when initially prescribing medicine to the patients.
"One of the genes makes the protein that metabolizes Warfarin in the liver, affecting how quickly or slowly it will break the drug down," Johnson said. "The other gene makes the protein that the Warfarin acts on, and so, it influences how much protein is present."
The more protein present in the body, the higher amount of Warfarin needed.
About 46 percent of the patients in the study benefitted from these genetic tests because they did not need the average 5 milligrams of Warfarin usually prescribed.
"Some people require less than 3 mg or greater than 7 mg," Johnson said. "It's a pretty significant overdose (…) or under dose.
Zumberg said genetic variations indicate a part, but not all, of how much doctors need to prescribe. He believes a patient's diet and use of other medication also plays a role in detrimining dosage.
"I'm not convinced it's a huge gain yet," he said. "I think it will get you to the right dose quicker, but I'm not convinced how quickly you'll get the information."
Zumberg's biggest concerns are cost effectiveness and turn around time for test results.
He believes that doctors should use the genetic information if it's readily available, "but it's not the end all and be all of Warfarin," he said.
