Another very common term I’ve heard in the ER is a “D-Dimer.” I mainly hear it with patients who are short of breath and are being evaluated for a pulmonary embolism. Let’s find out what exactly a D-Dimer is.
First we need to talk about a very important duo in medicine: plasmin and fibrin and their precursor enzymes: plasminogen and fibrinogen. We’re first introduced to fibrinogen when we learn about the composition of blood. Blood contains two main components, plasma, and formed elements:
Plasma (55%)
Water (92%)
Plasma Proteins (7%)
Fibrinogen
Albumin
Globulins
Other Solutes (1%)
Formed Elements (45%)
Red Blood Cells (99.9%)
White Blood Cells & Platelets (<.1%)
Formed elements are made up of red blood cells (99.9%) and white blood cells & platelets (<.1% each). So yes, nearly 45% of our blood is straight red blood cells. Well where does fibrinogen come in? Well the other 55% of blood composition is plasma. This is composed of 92% water, and 7% of what are called plasma proteins (the other 1% is “other solutes”). Within those plasma proteins we find fibrinogen (the others are albumin and globulins).
We can think of our bloodstream as a river, because well half of it is water. And swimming through it are a ton of salmon, like a ton of them (red blood cells). Plasma proteins are like the other animals just chilling in the river (otters, bears, beavers), far outnumbered by the salmon and let’s say one of them is a beaver. The beaver is fibrinogen and is a critical component of a blood clot (hey, let’s call that blood clot a dam in the river!).
When our body needs to stop bleeding, it activates hemostasis (meaning a halt of blood), which includes the vascular, platelet, and coagulation phase. Fibrinogen is actually soluble so it would just wash away in the stream, but it’s activated by an enzyme called thrombin into its active, insoluble form, fibrin.
Thrombin acts on Fibrinogen (found in blood plasma) to activate it to insoluble Fibrin
Insoluble fibrin produces blood clots, or thrombi; fibrin is like logs in a damn. So our fibrinogen beaver just needed some inspiration before doing what he does best which is why thrombin comes along and cheers him on. But here’s the thing right… blood clots can be dangerous. If this big fibrin damn were to break off and form an embolus (a traveling thrombi), it could block off a part of the river that we don’t want blocked and that could mean big trouble.
Just for the sake of my dumb river creature metaphor, we aren’t blocking off the entire blood vessel when it’s bleeding. It’s like if the river spills over a bank into an area it’s not supposed to go, or breaks a levy, so we need to dam off that section to ensure all of the water is moving downstream where we want it.
So after the fibrin dam is built and bleeding stops, and our body recognizes that it’s all done with the fibrin dam / blood clot, it calls in the clean up crew to break it down. Enter fibrinolysis, which by its name we can see means the lysis (disintegration) of fibrin. Two enzymes come in to call the shots for the clean up crew, tissue plasminogen activator (tPA) and thrombin again (which is pretty interesting).
Thrombin is like the superintendent of this whole project, noticed the dam is complete, and calls in the clean up crew. This clean up crew is composed of something called plasmin.
Thrombin and tPA activate a proenzyme plasminogen to produce the enzyme plasmin, which can digest the clot and break it up. So it’s fibrin and plasmin, fibrin and plasmin. The clotter and the digester.
And plasmin is going absolutely ham on this clot. So there’s pieces of wooden fibrin flying everywhere. A type of this shredded fibrin, or a fibrin degradation product (FDP), is called D-dimer. It’s like the splinters and parts of a shredded log. D-dimer isn’t normally present in our plasma unless some type of coagulation is happening, and thus the need for fibrinolysis has occurred. So if we notice D-dimer, a clot is being degraded, or attempting to be degraded somewhere in the body, which is an indication of a pulmonary embolism.
So here is sort of this whole process. We start with our soluble fibrinogen, which is then activated by thrombin. So then it forms this fibrin mesh, which I’m not sure is insoluble yet. It’s when Factor XIII (13) comes in (more on clotting factors later) that we form this crosslinked, insoluble fibrin mesh. Factor 13 is known as the fibrin stabilizing factor. And remember that plasmin is our clean-up crew that is deconstructing this crosslinked fibrin mesh, part of which is the D-Dimer. And we can see where the namesake comes from here. Fibrinogen has two “D” subunits, and the dimer (or two identical molecules) is two D subunits crosslinked together (both linked to an E subunit). But what does the “D” stand for!? I see there’s a D and an E domain of fibrinogen. I also see an alpha, beta, C, D, and E domain. So it’s just an alphabetical list and doesn’t stand for anything.
Pulmonary Embolisms
Okay so what exactly is a pulmonary embolism and why do we care about them? Well a thrombus is a blood clot and when it breaks off and starts to move, it’s called an embolus. See at first I thought a clot just sort of just appeared in the lungs. Or maybe it came from somewhere in the heart. So it turns out the most common source of these emboli are in the veins of our legs, known as deep vein thromboses. Blood in our legs already has a lot of work to do to fight the forces of gravity and come all the way up to reach the inferior vena cava and enter the right atrium. That’s why veins have valves in our veins to prevent backflow. Our muscles in our legs actually contract to help pump blood up through our veins.
The vasculature of our lungs is very expansive. It’d be quite easy for an embolus to get trapped there, and cause ischemia to lung tissue and alveoli, prevent oxygen exchange, and cause us to breathe faster to compensate, and eventually be short of breath. So the embolus starts in the leg, goes into the right atrium via the inferior vena cava, and then the right ventricle, and then through the pulmonary trunk into the pulmonary arteries. So it’s deoxygenated blood that gets trapped, never getting the chance to get oxygenated. It can’t really go any further, right? It’s lodged there; the vasculature just keep getting smaller.
The interesting thing is that if you have a high risk patient, like a patient who just had surgery and is immobile for a while (there are other factors), you should just go straight to imaging (CT scan) and skip the D-Dimer as a screening test. A special type of a CT, called a CTA scan (CT angiography) with contrast to show the blood vessels in the lungs can be used.
So what’s the treatment for a PE? You can use a blood thinner to help prevent existing clots from getting bigger and from other clots forming. Some clots dissolve on their own.
Clotting Factors
In my research, I came across the mention of several clotting factors. There are 13 of them, named by roman numeral, in the order they were discovered. Our beaver fibrinogen is actually Factor I (fibrin I’ve seen is Ia) Factor II is prothrombin. Factor XIII (13) is involved in the creation of insoluble fibrin.
It’s also worth noting that there is a pretty extensive coagulation cascade with an intrinsic and extrinsic pathway featuring all of these clotting factors, but I think that’s outside the scope of this post.
Sources
Martini F, Nath J, Bartholomew E. Fundamentals of Anatomy & Physiology. 2018. Eleventh Edition. Pearson Education.
Bounds EJ, Kok SJ. D Dimer. [Updated 2021 Jul 14]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK431064/
National Center for Biotechnology Information (2022). PubChem Compound Summary for CID 439199, Fibrin. Retrieved March 3, 2022 from https://pubchem.ncbi.nlm.nih.gov/compound/Fibrin.
Mpt-matthew, CC BY-SA 3.0 https://creativecommons.org/licenses/by-sa/3.0, via Wikimedia Commons. https://commons.wikimedia.org/wiki/File:D-dimer_production.pdf
https://www.mayoclinic.org/diseases-conditions/pulmonary-embolism/diagnosis-treatment/drc-20354653