Transcription
At this point, we have indeed discussed the entire hemostasis process. But of course, the formed clot cannot remain in the bloodstream forever. At some point, it must disappear. Therefore, we will now talk about the processes that occur after hemostasis. And essentially, we are talking about two very important processes here: clot retraction and the subsequent fibrinolysis.
Clot retraction occurs within a few hours after hemostasis, while fibrinolysis is a longer process that takes place over several days. Clot retraction begins approximately 1 hour after primary and secondary hemostasis have been completed, whereas fibrinolysis starts about 2 days later.
Let's begin with clot retraction. So, once both primary and secondary hemostasis have been completed, as mentioned, about an hour later, certain changes occur in platelets. We have already discussed that platelets contain actin and myosin. The mechanism is quite similar to that in skeletal muscle in terms of how these two proteins function. And over the following hours, actin and myosin contract in a way similar to skeletal muscle, thereby tightening the fibrin strands. Just like in skeletal muscle, this process requires ATP, meaning energy is needed. ATP reserves are found within the platelets themselves, by the way.
As a result, the clot contracts, and fluid is squeezed out of it. This fluid is called serum. As a note, you already heard that in another lecture, serum is the liquid part of blood without fibrinogen and other coagulation factors. Because of this, serum is often used in laboratory tests, diagnostics, and immunotherapy. For example, in the production of antibody preparations, as well as in research where stable biological fluid is needed since it cannot clot.
Now, as the fibrin strands are pulled tighter together, the edges of the wound draw closer together, and the clot becomes smaller in size, but also stronger. This process also helps prevent scar tissue formation, and it can be compared to the work of a surgeon stitching a wound together. Here, the threads are fibrin strands, which are tightened together by the action of actin and myosin within the platelets.
Speaking about scar tissue, if the wound is larger and clot retraction is not sufficiently effective, the empty spaces are filled with collagen or connective tissue, and in that case, scar tissue forms. That is why medical professionals must always evaluate what to do, whether a wound should be left to heal naturally or stitched together. Maybe larger wounds should be stitched together, as this helps prevent scar formation and supports proper natural hemostasis followed by effective clot retraction. And that concludes clot retraction.
Next comes fibrinolysis. It is not immediate, as mentioned earlier. It begins approximately 2 days later, and here I need to introduce a few new substances, although the names are quite directly related to the process. I understand that they might get mixed up with everything else in hemostasis, but hopefully, that will not be the case.
First, fibrinolysis. The name itself already indicates what happens here. "Fibrino" comes from fibrin, and "lysis," as in hemolysis, means breakdown or destruction. Indeed, this process involves the breakdown of fibrin since healing has already begun, and the clot is no longer needed to remain in place permanently.
Let us start by the fact that another plasma protein is present in the blood, produced by the liver, of course, like most plasma proteins, and this protein is called plasminogen. Plasminogen is the inactive form, while its active form is plasmin. Plasminogen is converted into plasmin by another substance called tissue plasminogen activator, or shorter, TPA. It is called "tissue" because it's produced by the endothelial tissues, and "plasminogen activator" because it activates plasminogen into plasmin. So, but the abbreviation TPA is also commonly used.
And regarding this tissue plasminogen activator, the situation is as follows. Essentially, healthy endothelium releases only a very small amount of this factor on a daily basis, and therefore, only a small amount of plasminogen is converted into plasmin, a negligible amount. However, when secondary hemostasis occurs, the endothelium comes into contact with substances such as activated factor 10 and thrombin. It should be recalled that thrombin is the activated form of factor 2. And upon contact with these substances, the endothelium begins to release a large amount of tissue plasminogen activator. As a result, a significant amount of plasminogen is converted into active plasmin.
The substance that plays the main role in fibrinolysis is therefore plasmin. So now, I explain why plasmin has the key role in fibrinolysis. The function of plasmin is to break down the fibrin strands, thereby releasing the trapped platelets as well as other blood cells. These broken-down fibrin strands are called fibrinopeptides, as they are, of course, proteins. As a result, the clot is dissolved.
And interestingly, tissue plasminogen activator, which activates plasmin, can also be used clinically to dissolve thrombi because plasminogen is already present in plasma and can simply be converted into plasmin. Then, the smallest fibrinopeptide fragments are called dimers. This is important because there is a specific blood test that measures D-dimer. An increased level of these dimers indicates active fibrinolysis in the body, since they appear in the blood only when clots are being broken down. Therefore, elevated D-dimer levels suggest that clots have formed and are undergoing degradation.
You might wonder why fibrinolysis does not start immediately since plasmin can be formed quite early. Why does it not dissolve the clot right away? The reason is that in the body, hemostasis, fibrinolysis, coagulation, and anticoagulation are all maintained in a continuous balance, and the same applies to fibrin activity because all of this is very tightly regulated. Of course, the entire regulatory system is actually much more complex than what I am explaining to you, but I am focusing on the most important and essential aspects.
Returning to fibrinolysis regulation, it is important to note that another protein present in plasma, and by now you probably understand that the initial introduction of the three main plasma proteins was just a starting point, and that each lecture more plasma proteins are added, and I'm sorry about that. Well, this next protein is called alpha-2 antiplasmin. Its name already suggests that it acts against plasmin. Indeed, this protein can inhibit the activity of plasmin, which is its main function. In addition, when a clot is formed, activated factor 13 ensures that this substance is incorporated into the clot by binding it to fibrin. Therefore, when a clot is freshly formed, alpha-2 antiplasmin is present in relatively high concentration. Then, over time, it is gradually washed out since the clot is located in a fluid environment, so it washes out. However, while its concentration remains high, antiplasmin inhibits plasmin activity, thereby preventing premature fibrinolysis. Then, approximately on the second day, when alpha-2 antiplasmin has been sufficiently reduced, plasmin begins its role of breaking down fibrin, and complete fibrinolysis occurs.
In everyday conditions, antiplasmin is also important for maintaining balance in fibrinolysis processes, not only in wounds but also in cases of unintended clot formation within the circulation. And now, once the clot has been removed, we can say that the process of hemostasis has been fully completed.