What do you really know about coagulation at this very moment?
You know: Coagulation – the thing with the y-shaped coagulation-cascade containing a lot of factors and co-factors that stop bleeding…
To be honest with you, when I started with my residency in anesthesiology and critical care I had no idea! Really, NO IDEA! There were only two things I knew:
- Coagulation is a very complicated thing – I never understood it so I only learned the cascade for the exams (…and the half life of that type of knowledge is approximately one to two months in my case).
- Bleeding naturally stops by itself, severe bleeding needs a surgeon and if your patient suffers from a bleeding disorder you need a specialist or you are f***ed.
What changed things completely was a phone call from my head of department. His secretary called me two months before my residency started and patched me through him:
Head of dptmt: “Hello?”
I: “Good morning sir, thank you for calling. How can I be of any help?”
Head of dptmt: “What do you know about coagulation?”
I: [F**ck – I don’t know anything about coagulation and he is testing me – I won´t get the job]
“Sir, well, ahm, I know a lot about coagulation. What exactly do you want to know?”
Head of dptmt: “Not to worry. I know a lot about coagulation too, I´ve written a book on it, you know? But my question aims on what do YOU know about coagulation. You will start your residency at our hospital in two months and we deal a lot with bleeding in our job. But this shouldn´t be entirely new to you.”
I: [OK, it was the job of my dreams but I won´t get it. I just screwed it up. F***!]
“Of course I knew sir, coagulation is the “thing” with the coagulation cascade and…”
Head of dptmt: [laughing] “I see. You don´t have a clue. That´s what I suspected… [meaningful brake]
But don´t worry. It is the same with all our new residents. Because we know that, we send all of them on training when they begin their residency. It´s a course lasting for two days. It is like a boot camp on dealing with severe bleedings and understanding the mechanisms of coagulation. I think your participation is a good invest. Angela [the secretary] will clear the details with you.”
I: [sighing with relief] “Thank you. That sounds great, sir!”
So in the nick of time I started learning a lot about coagulation. And how did I do that? I fetched my biochemistry textbook and repeated the facts I already learned for the exam years ago. I did so too with the pathology textbook and the physiology textbook. And of course I googled and wikied coagulation. I swear I was able to recite and draw the coagulation cascade backward and forward although I had to admit that it was much more reciting than understanding.
And then in the autumn of 2009 the training (Basics on Coagulation for anaesthesiology and intensive care) started with it´s first lecture which was titled “Coagulation to the point – Basics for everyday life” by Georg Pfanner who is a brilliant speaker and has meanwhile become a friend of mine.
He roughly started in that way:
“Well, we all know that coagulation was explained by the coagulation-cascade for centuries but by no later than the landmark publication of the cellbased modell on coagulation in 2001 by Hofman and Monroe (Thromb Haemost 2001; 85: 958–65) we all know better. So nowadays nobody tries to explain coagulation by using the coagulationcascade from 1964 only.…”
I sat there and felt like being the biggest idiot on earth. But it got even better. About an hour after Georg Pfanner, Lars Asmis, head of the center for perioperative thrombosis and hemostasis in Zürich, disassembled my reality with his lecture on perioperative lab-testing on bleeding risks. “As you all know flipping a coin has the same prediction probability for a severe perioperative bleeding as the classical standard lab tests PT (“Quick”), aPTT and platelet count. So why are some institutions still using them prior to operations?”
On this day I learned more about medicine than in some months at the university. This evening I didn’t attend the (great & *yummy*) dinner. I sat in my room, read the course script and spent about 40 Euro on wifi vouchers (which were really expensive at that time). It was one of that aha-moments where you are far too excited to sleep because you realize that you will really need every bit of that knowledge to become better in medicine.
That night I slept 2 hours and the next day became even better than the first one.
Of course there was still a lot to learn about coagulation so I attended this course four times in the last years.
In the year 2009 my interest on coagulation and the management of bleedings awakened and today I am not only still interested in coagulation – I am excited and enthusiastic on coagulation because it is such a fantastic system that prevents us from loosing our blood [our life] on the one hand and from dying of thrombosis on the other hand. And, what is more important, I need this knowledge every day to be a better doctor for my patients. Today I´m co-author of the book “Gerinnung im klinischen Alltag” (a textbook on coagulation for the clinician) member of “Gerinnungsgruppe Süd” (an expert group on coagulation) and teach masterclasses on coagulation and the management of bleedings (gerinnung.net and medsimlinz.com). The textbook “Anästhesie griffbereit” which I am the author from contains of course a chapter on the management of severe bleedings and the understanding of coagulation.
So let´s start and give me the chance to fill you with enthusiasm too.
First of all let me explain you the concept of this article series.
This series contains five articles.
- What do you really know about coagulation at this very moment?
– Understanding the very basics of coagulation.
- Background check
– Some (maybe even historical) facts you should know for better understanding.
- Putting the pieces together
- How to measure coagulation
- Therapy & management of severe bleedings
After reading through the articles you should have a good overview about up to date concepts on the management of severe bleedings and the coagulation system. I will keep it short and sweet. We will only hit pathophysiology and all of the stuff that could be boring if it is important and will not dwell on too many theoretical concepts. It will be more like cupcake recipes. They are simple but they work in the real world – and cupcakes can be really delicious!
Coagulation is simple – but ill understood.
Coagulation describes the process which stops bleeding if a vessel is injured – that´s it.
Let´s split the explanation up into small and easy to chew pieces.
Our body stops bleeding by building a thrombus which occludes the injured vessel. That thrombus is made up from platelets which are “tied together” by fibrin. Because flowing blood contains a lot of erythrocytes they too can be found in every thrombus even if they play a minor role in the coagulation process.
Lets´s simplify this process to the max and take a closer look
Endothelium covers the inner wall of every vessel. This thin layer of tissue is the barrier between flowing blood and subendothelial tissue. If the endothelium is injured the subendothelial tissue is exposed to flowing blood containing the inactive coagulation system. Collagen and Tissuefactor (TF) are the most important activators of the coagulation process in the subendothelial tissue.
Tissue factor is a protein which can be found on the majority of cells (or can be expressed on their surface) which normally have no contact to the coagulation system (flowing blood). Tissue factor acts as a high-affinity receptor for the coagulation factor VII and can activate factor VII to factor VIIa which starts the coagulation process. Tissue factor is called tissue factor because it can be found on nearly all tissues except the ones having contact to flowing blood.
If the vessel wall is damaged, flowing blood (containing inactive coagulation factors) gets in contact with tissue factor bearing cells (subendothelial tissue). Coagulation factor VII (inactive in the flowing blood) gets in contact with Tissue Factor it is activated to coagulation factor VIIa (a stands for “active”) and the coagulation process is started.
Coagulation factors in the flowing blood plasma are called the “plasmatic” component of coagulation.
Platelets are called the cellular component of the coagulation.
So how does that work:
You have heard and read a lot about the Y-shaped coagulation cascade? But did you ever realize that the whole cascade is there for only one purpose? It is actually only there to control this one crucial last step, to activate fibrinogen to fibrin.
So let´s repeat this. The whole hard to learn and ill understood coagulation cascade has only one purpose – it controls the activation of fibrinogen to fibrin.
Sounds easy, doesn´t it?
The purpose of the coagulation cascade is to control its crucial last step, the activation of fibrinogen to fibrin. This fibrin is needed to tie the platelets together and so build a thrombus. The coagulation factors which are described in the coagulation cascade are called plasmatic part of the coagulation process – because they are part of the flowing blood (more exactly: blood plasma). The platelets which primarily stop a bleeding by adheration, activation and aggregation are called cellular part of the coagulation process.
For a better understanding imagine a brick wall.
A brick wall consists of bricks and mortar.
To get a stable wall you have to use a balanced proportion of bricks and mortar.
If you have little mortar and only stack the bricks on each other you will get a very unstable wall as result. If you lean against such a wall, this wall is very likely to break down.
If you build a wall out of huge amounts of mortar but only a few bricks you will get a very expensive but nevertheless very stable wall.
You can use this analogy on coagulation.
Imagine the platelets as bricks and the fibrinogen as mortar.
Under normal conditions you need a balanced amount of both to build a stable wall (thrombus).
If you build your wall (thrombus) out of a lot of platelets but to less fibrinogen, your wall (thrombus) will be very unstable.
If you construct your wall (thrombus) by using a lot of mortar (purified fibrinogen concentrate) but only a few bricks (platelets) you will get a very expensive but yet stable wall (thrombus) anyhow.
If you are now thinking that the author of this article has maybe spent too much time playing with his kids and is now subsequently writing very infantile posts you are maybe right. (I have to admit that after being “forced” to watch felt 1000 episodes of Bob the builder by my kids – I finally love Bob the builder.). But trust me – this is the far best analogy for coagulation I know and it can help you a lot if it comes to therapeutic decisions as you will see later. If you were expecting a more scientific post – stop reading now. It won´t get more scientific (… but because I know that we are all a little bit nerdy, I will include some links to the underlying literature…).
The ingenious brick wall model [i] was published by Thomas Lang et al. in 2011 on the basis of the observations they made [ii] 2009. It is used since then to explain parts of coagulation with great success.
The Group around Petra Innerhofer and Dietmar Fries (University of Innsbruck ) was able to visualize what Thomas Lang described later as brick wall model. They constructed a porcine model on dilutional coagulopathy and got awesome electron microscopic pictures from a thrombus under normal, diluted and resubstituted with fibrinogen conditions [iii]. You will find the full text containing the pictures here (http://bja.oxfordjournals.org/content/95/2/172.full). Look especially at the figures 3, 4, and 5 (which you can also download directly as powerpoint slides free for teaching purposes) and think of the brick wall model while watching the pictures.
So – what do you know about coagulation at this very moment?
At this point you should know what a thrombus is made of and how it looks like (brick wall).
In the next post I will tell you more about the unloved y-shaped coagulation cascade and why knowing more about it can be very useful for your daily practice….
[i] Lang, T. Med Klin (2011) 106: 171. doi:10.1007/s00063-011-0018-5
[ii] Lang T, Johanning K, Metzler H et al (2009) The effects of fibrinogen levels on thromboelastometric variables in the presence of thrombocytopenia. Anesth Analg 108(3):751–758
[iii] Effect of fibrinogen on reversal of dilutional coagulopathy: a porcine model, Br. J. Anaesth. (August 2005) 95 (2): 172-177. doi: 10.1093/bja/aei160