D-dimer

 

Q. What is the difference between FDPs and D-dimers?

A. Fibrin degradation products (FDPs) and D-dimers are both little fibrin-containing molecules that you can measure in the blood. There’s an important difference between the two, though, that I’ll mention in a minute.

Making a clot
When you make a blood clot, the first thing you do is make a little mushy plug of platelets to fill in the hole in the vessel. Then, you make fibrin (from a bigger molecule called fibrinogen) which sticks to the platelet plug like superglue and seals it up.

If you want to break down the clot, a substance called plasmin can attack the fibrin in the plug, chopping it up into little fragments called fibrin degradation products, which you can measure in the blood. This breakdown process actually starts happening almost right away, as soon a clot is being formed (in this context, it’s called remodeling). Which makes sense, if you think about it – you want to keep the clot limited to the necessary size/place (otherwise, it would fill up the whole vessel, which could be a disaster).

Testing for thrombi
If you want to find out if someone has a thrombus (a big clot, like a pulmonary embolus, that is causing problems for the patient), you can look for fibrin degradation products in the blood, the idea being that if you see a lot of them, it probably means the patient has a thrombus somewhere that is being remodeled. There are a couple problems with the test though. One is that the test is SUPER SUPER sensitive. Meaning that even small, normal clots give off enough FDPs to make the FDP test register as positive. More on that in a minute.

The second problem is that FDPs can be created from circulating fibrinogen too (not just from busting up a clot). So if you see FDPs, you don’t really know if they came from a clot or not.

D-dimers vs. FDPs
Enter the D-dimer. D-dimers are little chunks of broken up fibrin, like FDPs, but with an important difference: they contain an extra little linkage. When fibrin seals up a clot, there’s actually an extra, final step in which factor XIII creates little cross-links between the fibrin molecules. When the fibrin in a clot is busted up, some of the resulting fragments will contain these little cross-links. These little fragments contain one “E” fibrin subunit and two “D” subunits (check out the diagram above), and are called D-dimers.

D-dimers are more specific for actual clots than FDPs are – because you only get D-dimers from the breakdown of real clots (not from the breakdown of fibrinogen). ย Tests that specifically look for D-dimers were developed in the 1990s, and most labs use these D-dimer assays now instead of assays that measure FDPs.

Best use of the D-dimer assay
That’s all well and good – but we’re still left with the issue of the super-sensitivity of the test. If you see D-dimers in the blood, it might mean that there is a thrombus somewhere – or it might mean that the patient simply has a normal clot or two. Another way to put this is that the test is SUPER sensitive, but not very specific. How to get around this problem?

The best way to deal with this is to use the test to rule out a thrombus but not to rule in a thrombus. If the D-dimer (or FDP) assay is positive, it doesn’t really tell you a heck of a lot – so it’s not great for ruling in a thrombus. However, if the test is negative, you can be dang sure that the patient does not have a thrombus. So it’s great for ruling out a thrombus.

The test is often for this purpose in the emergency room, in patients that come in with symptoms of pulmonary embolus (PE). If you do a D-dimer assay and it comes back negative, then you know that there isn’t a PE, and you better start looking for something else.