Genetics determine optimal drug dose of common anticoagulant

August 21, 2007

Genetic testing can be used to help personalize the therapeutic dosage of warfarin, a commonly-used anticoagulant, according to research published in the September 1, 2007, issue of Blood, the journal of the American Society of Hematology. This result represents one of the first applications of using an individual’s genetic information to guide personal medical care.

Because individuals metabolize drugs differently, varying doses of warfarin are needed for the drug to be effective in each patient. Too much warfarin can cause severe bleeding, and too little can cause dangerous blood clots. Currently, there is little guidance for predicting how much of the drug a person will need. Physicians have had to roughly estimate an initial dose of warfarin and then continually monitor a patient’s International Normalized Ratio (INR) value (a measure of how fast the blood clots), during treatment to tweak the dosage by trial and error.

For the first time, a group of St. Louis researchers combined the standard INR method with genetic testing to predict the therapeutic warfarin dose. Since warfarin is often prescribed after major orthopedic surgery to prevent blood clots in the legs, the study followed 92 adults undergoing either total hip or knee replacement at the Washington University Medical Center, who had never previously taken the anticoagulant.

Prior to warfarin treatment, the researchers collected blood samples and each patient’s medical history. The blood tests were used to examine variations in two genes, CYP2C9 and VKORC1, that may affect warfarin dosing. Variants in CYP2C9 impair the body’s breakdown of warfarin; variants in VKORC1 cause increased warfarin sensitivity. The patients were assigned initial doses of warfarin based on clinical factors and their genotype. The researchers followed the patients until successful treatment outcomes were achieved several weeks later.

By combining variants in these genes with initial INR response and other clinical factors, the researchers derived a dosing equation that estimated the therapeutic warfarin dose. The researchers found that these two genes were important in predicting the response to warfarin. Additional factors, such as blood loss during surgery and smoking status, also correlated with therapeutic dose.

Using these data, the researchers developed a therapeutic model that could be used by physicians to refine warfarin dosage with greater accuracy than clinical factors alone. The researchers have made this dosing model publicly available on a free Web site, www.warfarindosing.org, and are now validating it in orthopedic and non-orthopedic patients beginning warfarin therapy.

If validated, particularly in patients taking warfarin for reasons other than orthopedic surgery, such as to prevent stroke, this gene-based dosing could predict a safe and effective warfarin dose at the start of treatment, thus minimizing the risks of the current trial-and-error approach.

Source: American Society of Hematology

Explore further: A Christmas spice that may reduce your blood cholesterol

Related Stories

A Christmas spice that may reduce your blood cholesterol

December 22, 2017
Cinnamon is a popular spice at Christmas time, used to flavour everything from mulled wine to pumpkin pie. And, unlike many Christmas foods, this one might actually be good for you.

Heart patients who take vitamins less likely to take medication as prescribed, according to study

November 14, 2011
Atrial Fibrillation patients who are prescribed the powerful blood thinner warfarin often take it with vitamins or supplements that can hamper its effectiveness, or skip doses completely, increasing their risk for stroke, ...

Clot-busting drug safe for stroke patients taking blood thinner

May 10, 2012
Acute ischemic stroke patients taking the blood thinner warfarin can be treated safely with the clot-busting drug tissue plasminogen activator (tPA), according to research presented at the American Heart Association's Quality ...

Researchers find safer way to use common but potentially dangerous medication

February 29, 2012
A team of global scientists, led by researchers at Intermountain Medical Center in Salt Lake City, has developed a safer and more accurate way to administer warfarin, one of the most commonly prescribed but also potentially ...

One-third with common irregular heartbeat don't take blood thinners

January 6, 2017
(HealthDay)—Many people with the heart condition known as atrial fibrillation stop taking the blood-thinning medication that's prescribed to help prevent a stroke, a new study reveals.

Blood thinner dangerous for patients with artificial heart valves, study finds

September 26, 2013
(HealthDay)—When used by patients with mechanical heart valves, the blood thinner Pradaxa raises the risk of both dangerous clots and bleeding around the heart, a new study says.

Recommended for you

15 new genes identified that shape human faces

February 20, 2018
Researchers from KU Leuven (Belgium) and the universities of Pittsburgh, Stanford, and Penn State have identified 15 genes that determine facial features. The findings were published in Nature Genetics.

New algorithm can pinpoint mutations favored by natural selection in large sections of the human genome

February 20, 2018
A team of scientists has developed an algorithm that can accurately pinpoint, in large regions of the human genome, mutations favored by natural selection. The finding provides deeper insight into how evolution works, and ...

New software helps detect adaptive genetic mutations

February 20, 2018
Researchers from Brown University have developed a new method for sifting through genomic data in search of genetic variants that have helped populations adapt to their environments. The technique, dubbed SWIF(r), could be ...

Highly mutated protein in skin cancer plays central role in skin cell renewal

February 20, 2018
Approximately once a month, our skin completely renews itself. If this highly coordinated process goes awry, it can lead to a variety of skin diseases, ranging from skin cancer to psoriasis. Cells lining such organs as skin ...

Study of smoking and genetics illuminates complexities of blood pressure

February 15, 2018
Analyzing the genetics and smoking habits of more than half a million people has shed new light on the complexities of controlling blood pressure, according to a study led by researchers at Washington University School of ...

New mutation linked to ovarian cancer can be passed down through dad

February 15, 2018
A newly identified mutation, passed down through the X-chromosome, is linked to earlier onset of ovarian cancer in women and prostate cancer in father and sons. Kunle Odunsi, Kevin H. Eng and colleagues at Roswell Park Comprehensive ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.