One of the significant secondary side effects resulting from of our advanced prostate cancer treatments can be blood clots. Blood clots are potentially dangerous as they can lead to heart attacks, strokes and death. Warfarin is one of the drugs commonly prescribed to prevent these dangerous blood clots from ever forming. However, dosing of Warfarin is very difficult for doctors because each person’s ideal dose varies widely and is hard to predict, yet it is crucial for our safety.
Getting the wrong dose of warfarin can be dangerous—if the dose is too high, we can bleed profusely; and out of control, if it is too low, we could still develop the life-threatening blood clots. Doctors know that each person responds differently to warfarin. The problem is that one person may need 10 times more of the drug than another may, so it is challenging to figure out where to start the dosage levels. Typically, doctors are forced to start the initial dose based on standard clinical factors—such as age, weight and gender. They then are required to fine-tune the dosage over a few weeks in response to periodic tests of the blood’s ability to clot, possibly leaving us in danger of either bleeding out or developing blood clots.
In an attempt to get better information about proper dosing a study was conducted which evaluated information from thousands of genetically and geographically diverse patients. The international research team was able to develop a way to use an individual’s personal genetic information that could help determine optimal warfarin dosing. The results of the analysis are published in the Feb. 19 issue of The New England Journal of Medicine.
To investigate this issue, researchers from more than 20 teams in nine countries on four continents formed the International Warfarin Pharmacogenetics Consortium (IWPC).
They pooled their data so they were able to evaluate the data from about 5,700 people on stable dosages of warfarin. For each patient, the data included demographic information like age, gender and race; CYP2C9 and VKORC1 variants; and initial, as well as optimized, warfarin dosages.
Warfarin dosages was calculated in three ways—one that relied on the standard, clinical information, one that included additional information about individual patient variation in CYP2C9 and VKORC1, and one that used a fixed dose per day. Then they checked how closely their computational predictions matched the actual, clinically derived stable warfarin dosage for each patient.
The results revealed that when genetic information was included, the predictions of ideal dosages were more accurate, especially for patients at the low or high ends of the dosing range. This is meaningful because nearly half of those on warfarin are at the extremes of the range, and these patients are typically at the greatest risk for excessive bleeding or clotting. By quickly optimizing dosages for these patients, doctors could minimize dangerous complications and improve the effectiveness and sa