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What is the d-Dimer test?

Henry I. Bussey, Pharm.D., FCCP, FAHA
October, 2005
Updated August, 2006

This question has both a simple and a complex answer. The simple answer is that the d-Dimer test is a blood test used to rule out active blood clot formation. If you have a negative (normal) d-Dimer result, that nearly rules out the possibility that you have a blood clot actively forming. If you have an elevated d-Dimer test reult, that does not mean that you have a blood clot; rather an elevated d-Dimer result means that additional testing may be needed to see if a blood clot exists.

If you would like to know more detail about the d-Dimer test, read on...

When the clotting system is activated to form a clot, part of the process produces a substance called thrombin. Thrombin has several functions, one of which is to covert a clotting protein, fibrinogen, to fibrin. Fibrin molecules then link together to form a net of protein strands that form the basis of the clot. One of the other functions of thrombin is to activate the body's own clot dissolving ("fibrinolytic") system. In this manner, thrombin both activates the last step in the clot formation process, and it activates the system that helps dissolve clots. These two opposing functions ideally help the body form a clot where it is needed while, at the same time, limiting the size of the clot so that excessive clotting does not occur. When the body's clot dissolving system starts to dissolve the clot, that produces fibrin fragments known as d-Dimers. An increase in d-Dimer levels may mean that the clot dissolving system has been activated; but d-Dimers also can be increased by other factors such as infection, inflammation, pregnancy, etc.

Even though an increased d-Dimer level may reflect clot dissolving activity, the ability of the clotting system to turn on the clot dissolving system is so predictable that the d-Dimer test is now used to determine if the clotting system is active. If the d-Dimer blood test is negative (or normal), that virtually rules out active blood clot formation with a greater than 95% certainty. If the d-Dimer test result is above normal, that does not mean that you have a blood clot because other factors (such as infection, inflammation, pregnancy, etc.) can increase the d-Dimer. A d-Dimer test result above normal means that further testing may be needed to see if there is a clot. In other words, a normal d-Dimer can virtually rule out a new blood clot, but an elevated d-Dimer will not confirm that a clot is there.

There are instances in which a patient may have a new clot and not have an elevated d-Dimer, but these instances are rare (less than 5% of patients). Patients with less clinically important clots (small clots and/or clots in superficial veins) are more likely to have a normal d-Dimer.

I asked three of ClotCare's editorial board members for their comments about the limitations of this test. Dr. Goldhaber pointed out that the test relies on the patient having at least some fibrinolysis (clot dissolving activity) and that as many as 1% to 5% of patients may not have such clot dissolving activity at the time they are tested. Dr. Lyons also pointed out that the d-Dimer level may normalize as soon as 3 to 5 days after starting therapy. Therefore patients with older clots might not have elevated d-Dimer values if the clotting system and the clot dissolving system have become inactive. Lastly, Dr. Ansell reminded us that the predictive value of the d-Dimer test also varies with the test that is used. The latex test is less sensitive such that a normal latex d-Dimer test rules out a new clot with about a 90% certainty. With the more sensitive enzyme-linked (ELISA) test, a normal test rules out a new clot with a 95% to 99% certainty. Even so, if the patient's history strongly suggests that a blood clot has occurred but the d-Dimer is normal, the clinician may decide to perform more definitive tests to identify or rule out the presence of a clot. With the "typical" presentation, however, a normal d-Dimer test usually indicates that no further testing for a clot is required. A recent study evaluated the question, "is it safe to omit additional diagnostic tests if a patient has a negative d-Dimer?" This study is summarized for healthcare professionals on ClotCare at www.clotcare.org/ddimerpediagnosis.aspx.

Finally, there is emerging data to support the use of the d-Dimer test as a way to stratify patients who may be at risk of a recurrent clotting event. When the treatment course for a patient's first blood clot is nearing completion, some clinicians will do a d-Dimer test just before stopping anticoagulation and then periodically after the anticoagulation has been stopped. If the d-Dimer remains normal (does not become elevated), that appears to be an indication that the patient is at a low risk of developing another clot. Alternatively, if the d-Dimer level is elevated at the time the anticoagulation is stopped, or if the d-Dimer level goes up after the anticoagulation is stopped, that may suggest that the patient is at an increased risk of developing another clot. Some clinicians think that if the d-Dimer increases in that setting, it may be reasonable to consider resuming the anticoagulation. I am, however, not aware of any studies to confirm or refute the value of restarting anticoagulation in this situation.

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Wednesday, April 16, 2014