Blood clots will be given a cap

Russian scientists have found out how blood clots form

Yana Komarova, "Newspaper.Ru"

How Russian biophysicists turned the idea of the formation of blood clots and the posthumous "caps" of platelets to the science department of the Newspaper.Ru" was told by Professor of the Department of Medical Physics of the Faculty of Physics of Lomonosov Moscow State University, Head of the Laboratory of Molecular Mechanisms of Hemostasis at the CCF of the Russian Academy of Sciences, Head of the Laboratory of Cellular Hemostasis and Thrombosis of the D. Rogachev FNCCDGOI, Doctor of Physico-Mathematical Sciences Mikhail Panteleev.

Why platelets need "caps"

"Platelet caps were discovered by our team in 2013, and since then they have become a recognized phenomenon," says Mikhail Panteleev.

Now scientists have taken another step towards deciphering the problem of blood clotting: in a new article published in the highly rated journal Blood (Podoplelova et al., Blood coagulation factors bound to procoagulant platelets are concentrated in their cap structures to promote clotting), they found that all the enzymes they had previously discovered are in the "caps". responsible for blood clotting. Most of the authors of the article are employees of Lomonosov Moscow State University. The work was carried out in cooperation with the Dmitry Rogachev Federal Research and Clinical Center for Pediatric Hematology, Oncology and Immunology, the Center for Theoretical Problems of Physico-Chemical Pharmacology of the Russian Academy of Sciences and the University of Strasbourg. The scientists' research is supported by a grant from the Russian Science Foundation (RNF).

"We have shown that blood clotting reactions take place in "caps" – special small structures on the surface of platelets (blood cells that are responsible for stopping bleeding). This is necessary in order to accelerate these reactions by two orders of magnitude (50-100 times) and prevent the leaching of coagulation enzymes from the thrombus," says Mikhail Panteleev.

Leaching of coagulation enzymes is dangerous because it can cause thrombosis downstream of the blood stream, as a result of which it becomes possible to "plug" the vessel with a part of the detached thrombus. This phenomenon, which causes horror in everyone who has heard of thrombosis, is called thromboembolism.

In order to prevent deplorable consequences, it is necessary to fully decipher the mechanism of blood clotting. Scientists are gradually explaining this process. The concentration of all enzymes and various proteins that mediate adhesion (cell fixation) in a small area - the "cap" – on the platelet surface, in addition to accelerating clotting reactions, ensures its attachment to the growing thrombus only in the "cap" area. This allows enzymes that could cause blood clotting outside the thrombus to be securely hidden in the body of the thrombus and inaccessible to the blood flow.

Overactivation or death

The process of platelet adhesion as a result of damage to blood vessels and the formation of strong aggregates to stop bleeding is called hemostasis (from Greek. haimatos – blood, stasis – stop). It is possible as a result of platelet activation. Activated platelets are different: simple (aggregating) and overactivated (procoagulant). Simple aggregating platelets form the main body of the thrombus. When activated, they take an amoeboid shape with multiple legs for better grip. Overactivated platelets are large and spherical, they increase several times compared to the inactive state. Such growth is possible due to the fact that the platelet has a source of a spare membrane – a huge network of membrane channels inside. The platelet is porous like a sponge before activation: it consists of half granules and membrane channels, therefore it can swell.

Platelets on a substrate, including procoagulant (red) with caps (green)

The platelet "learns" about the presence of damage with the help of various activators, the main ones among which are collagen, ADP and thrombin. Collagen is the main protein of the extracellular matrix (a three–dimensional grid of molecules responsible for connecting cells in the body tissue). ADP (adenosine diphosphate) is an adenine nucleotide contained in all cells of the body and involved in the energy of cells. Thrombin is the main enzyme of blood clotting and is produced during hemostasis or thrombosis. In a healthy body or with weak damage to tissues and organs, activators do not come into contact with blood, and with strong their appearance triggers the activation of platelets, their adhesion and the formation of a blood clot.

Activators stimulate the release of calcium ions Ca2+ into the platelet cytoplasm. As was recently shown by Mikhail Panteleev and colleagues from Lomonosov Moscow State University in an article in the Journal of Thrombosis and Haemostasis (Obydennyy et al., Dynamics of calcium spiking, mitochondrial collapse and phosphatidylserine exposure in platelet subpopulations during activation, platelet mitochondria collect calcium and when the concentration of calcium in them reaches a critical point, they stop all vital (metabolic) processes in the platelet. This means that the platelet dies (because of this it is called a "kamikaze cell"), thereby passing into an overactivated state. All processes of vital activity stop in it, it greatly increases in size, inflates – empty, like a bubble. And the enzymes necessary to accelerate blood clotting reactions are concentrated outside in a small "cap".

If in doubt, it is better to curl up

In general, the hemostasis system has a large margin of safety. It can be "spoiled" by genetic diseases, but this is rare. The most famous disease – hemophilia – occurs in one person out of tens of thousands, and the rest (for example, Glanzman's thrombasthenia, when platelets do not aggregate) – one in a million or less.

The structure of the thrombus

"In 50% of cases, the cause of death is that this function of our body (blood clotting) is not designed for a modern lifestyle, and this leads to mortality and disability. It is not designed for a sedentary lifestyle, an excess of fatty foods and a good level of medicine. The body is ready for the fact that a person moves a lot in conditions of lack of food and lack of medicine. Everything is like our ancestors," Mikhail Panteleev says ironically.

In some cases (in particular, during pregnancy, injuries, burns), the blood clotting process is started "just in case", which can lead to clogging of blood vessels and severe consequences. It turns out that the hemostasis system in the body works when modern medicine allows you to do without it. With injuries, it is now possible to save a person by stopping the bleeding, but the system is activated, and this can lead to death – paradoxically – from blood clotting during bleeding.

An imbalance in the hemostasis system (and its consequence – the formation of blood clots) occurs due to mutations, oncological diseases, infections, the formation of atherosclerotic plaques and stagnant blood zones, as well as injuries and burns. It is noted that atherosclerosis (the formation of cholesterol plaques on the walls of arteries) is the leading cause of mortality from thrombosis, because our body, the author of the study emphasizes, is not designed for an excess of fatty foods, the whole biochemistry of fat metabolism is aimed at storing and transferring hungry periods.

"Throughout the history of mankind (except for the last century, maybe), the risk of dying before the age of 20 from bleeding or blood poisoning was much higher than from atherosclerosis after 40 years. Therefore, all our protective systems, including hemostasis, are initially "twisted to the maximum". As a result, now most people die from heart attacks and strokes," says Mikhail Panteleev.

Another famous type of thrombosis is venous, largely due to its appearance to areas of stagnation in the blood. Venous thrombosis often occurs as a result of a sedentary lifestyle, which manifests itself in circulatory disorders.

"In the course of natural selection, a person was formed in conditions when he had to run, fight and work physically. Nature could not have foreseen office work and hours–long flights in an airplane," the scientist recalls.

In the conversation, Mikhail Panteleev stressed that this work (even the publication of the article in question) would have been impossible without the support of the project by the RNF grant, and explained why.

"I can only talk about the Russian Science Foundation with delight from the moment it appeared (even before I received the grant myself). The RNF grant gave my laboratory as a whole a huge push forward. Having decent funding for full–fledged fundamental research is a completely different level of work. In particular, the article in Blood became possible only thanks to the RNF. Suffice it to say that after its acceptance into print, only its publication (payment of page charges and color illustrations) it cost us about 350 thousand rubles.. Moreover, the article in Blood is only part of a large project within the framework of the RNF grant, and we have already published more than ten interesting articles under this grant, and each has its own search history. Since 2004-2005, there have been many positive changes in the support of science, which are noticeable even from my level as an ordinary scientist, but the creation of the RNF was a qualitative leap," says Mikhail Panteleev.

The text was prepared in cooperation with the Indicator project (Indicator.Ru ).

Portal "Eternal youth" http://vechnayamolodost.ru  05.09.2016