If you cut open a water pipe, water will continue to pump out of that hole while there is still pressure in the pipe, even if it drains the entire country dry. However, if you cut open a blood vessel, you are more fortunate: you usually don't continue to bleed until your heart stops (which is when the pressure subsides). The reason? Haemostasis.
Haemostasis is a big but important topic which I'll hopefully cover in more detail later. It basically involves (i) keeping the blood flowing smoothly under normal conditions, and (2) plugging any leaks the might arise in our vasculature.
Coagulation is one of three aspects to haemostasis (the other two are platelet plugging and endothelial changes). It is fundamentally a cascade whereby one inactive proenzyme is converted to an active enzyme, which in turn activates the next proenzyme. And so on. The enzymes and proenzymes here are called clotting factors.
Since at each step, the active enzyme can activate numerous inactive proenzymes, the process is exponential, quickly generating an enormous amount of the final element in the cascade - thrombin. Thrombin then converts the plasma protein fibrinogen into fibrin. Fibrin molecules are hard, insoluble strands, and they are crosslinked by another of the clotting factors (Factor VIII) to form a wire-like mesh that blocks the hole in the blood vessel. It does this in conjunction with the platelet plug that the platelets formed (but that's another story).
Now its obviously enormously important to break down this clot once the hole has been properly repaired, or else the obstruction will be permanent. Plasmin, formed from plasminogen, is the substance the body uses to break down fibrin. The resultant fragments are termed fibrin-degradation products (FDPs). There are lots of types of FDPs, but the one most commonly tested for in the labs is, of course, the D-dimer. Thus D-dimers are used as an indication of a clot having been formed (as it is now being broken down).
But why, out of all the FDPs, do we test for D-dimers so often? The answer is quite interesting. Fibrinogen is produced by the liver in any inflammatory process. The way the body gets rid of excessive amounts of it is very similar to the way the body gets rid of its cousin fibrin. Both processes produce FDPs, and thus FDPs will be elevated in some situations even when no actual clotting has taken place. However, the only way a D-dimer is formed is when crosslinked (by factor XIII) fibrin is broken down by plasmin. Thus, D-dimers, and not FDPs in general, are sensitive indicators of clot breakdown.
The main application of D-dimers has been to confirm the diagnosis of a deep vein thrombosis (DVT) or a pulmonary embolism. It is also sometimes used in the diagnosis of disseminated intravascular coagulation. Importantly, it's chief value has been to rule out, rather than rule in, these conditions. (It has a strong negative predictive value, but not a high positive predictive value.) In other words, if you find D-dimers, you know that clots are being broken down, but you can't be sure that the original clotting took place in the legs, lungs or systemically (to use the above three examples alone). D-dimers are also raised in:
- Cancer (probably reflecting a chronic low-grade DIC)
- Liver disease (due to decreased hepatic clearance)
- Post operatively (a normal response to the surgeon's damage)
- After significant bleeding (a normal response again)
- During pregnancy (a minor increase due to the body being more eager than usual to stop blood loss)
- ... and many other conditions.
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