Anke-Hilse Maitland van der Zee - Blood thinners at the right dose

A new DNA-test can help find the right dose for blood thinners against thrombosis. But is it ready yet for standard clinical practice?

Coumarins— blood thinners against thrombosis, or blood clotting, are amongst the most widely used drugs worldwide. Millions of mostly elderly people depend on them. But finding the right dosage is a painstaking process. The needed amount of medicine can differ tenfold from one patient to the next, and the consequences of getting it wrong can be severe. Coumarins are in the top three of drugs that cause hospitalisations.

The EU funded EU-PACT project, completed in 2013 developed a simple DNA-test that looks for two genetic variants and can predict the right dosage. But is the test ready to become standard practice prior to coumarin therapy? Project coordinator Anke-Hilse Maitland van der Zee, associate professor of personalised medicine at the University of Utrecht, the Netherlands, talks to about the perspective to improve the balancing act of getting the right dose of blood thinners to patients.

What happens if the dosage of coumarins is not right?
For instance, if it is too high, small cuts that never stop bleeding are a telltale sign. But it can be much worse, and cause extreme bruising and internal bleeding. This is what causes most of the hospitalisations.  If the dose is too low, then the coumarins have no effect. Blood clots will still be formed with all the damaging results.  

So how does the test that you developed actually work?
It is a really simple and accurate DNA test which we developed into a point-of-care test. The patient is tested in the doctor’s office, and gets the result within hours. Then his dosage will be adapted accordingly.  It had to be this quick because we expected the strongest effect within the first month of treatment. By the second and third months the proper dosage will be found anyway by simple trial and error.  But that can be very troublesome for the patient.

What were the results of your experiments?
If we take all three tested coumarins together, the proper dosage was found within 21 days instead of 29. We can do that, because the genetic variants have similar effects in all three. And in the first three months of treatment the patients spend 7% more time in the right range of dosage. Before it was 60%, with the DNA test it was 67%.

Is 7% a significant improvement?  
Maybe not, but that is a mean result taken from the total cohort of 500 patients who were in the experiment.  We expect a much stronger effect within the group of patients who indeed have the two genetic variants. Only we have not quantified that effect yet.

Should the DNA test be standard clinical practice before starting coumarin therapy?
That remains an object for future research. We still want to know how strong the effect will be in patients who are carriers of the genetic variants.  Also we want to do a cost-effectiveness analysis. We want to find out how expensive it would be to genotype all patients. Only once that has been done can we give real advice on whether we should we translate this into clinical practice or not. But if I needed a coumarin tomorrow, I would definitely want to know my genotype.

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