Hello, steemians! I hope you're doing fine, these days I was swinging on the internet without a real purpose (like I always do in my free time :p) until I found this very interesting research about a new medical technology that can save a lot of lives in the near future.Statistically speaking, many deaths across the world happen due to undiagnosed internal bleedings, the causes are multiple from simply ignored traumas to complex medical conditions.The digestive tract is the number one organ to blame because bleedings can go undetected in Feces.Now before we jump into this 'super-cool' technique we need to understand some basics of human physiology.

How does the body deal with bleedings?

When you are cut with a knife, you begin immediately bleeding but after a while, everything stops.The physiological process that took place is called Hemostasis, according to Wikipedia.

Hemostasis (derived from Hemo=blood and stasis=stop), is a process which causes bleeding to stop, meaning to keep blood within a damaged blood vessel (the opposite of hemostasis is hemorrhage). It is the first stage of wound healing. This involves coagulation, blood changing from a liquid to a gel.

Hemostasis is just a bunch of complex reactions (Don't worry, it's not so hard to understand), it's divided into three steps: primary hemostasis, coagulation cascade, and Fibrinolysis.Many factors are involved in the process, we will run them one by one.

A/Primary Hemostasis:

1/Essential Elements

Platelets: tiny disc-shaped cells (2 to 4 micrometer) rich in granules, they are produced in the bone marrow from a huge cell called megakaryocyte (derived from a hematopoietic stem cell) that divides into many platelets.

In the blood, the count of platelets is around 150 000 to 400 000 per mm3.On their surface they express two important receptors, Ib glycoprotein receptors (GP1b) and IIbIIIa glycoprotein receptors.

Glycoproteins are proteins that contain oligosaccharide chains (glycans) covalently attached to polypeptide side-chains, we will discuss their functions later.

Endothelial cells: These cells cover the surface of blood vessels.Normally they have antithrombogenic meaning they prevent blood clotting, but when they are damaged the sub-endothelial layer become exposed, this layer is very rich in structural proteins named collagens and can initiate blood clotting.

Von Willebrand factor(vWF): It's a very important glycoprotein produced generally by endothelial cells.vWF acts as a bridge between the collagen and the platelet, on one side it attaches to GP1b receptors and on the other side it attaches to collagen fibers.

This is a representative model of the interaction between the two glycoproteins, in blue the extracellular domain of GP1b and in yellow the vWF domain.Do you remember the granules of platelets? Well, they are released into the blood when the clotting process begins, they contain some of the vWFs to increase the adhesion even more.

Fibrinogen: It's also a glycoprotein produced by the liver but this time it's totally soluble.Its insoluble form is fibrin transformed from fibrinogen by a specific enzyme called thrombin in the second phase of hemostasis.Fibrinogen connects platelets to each other to strengthen the clot.

2/Formation of platelet plug:

After the rupture of a blood vessel, the subendothelial layer become exposed and the platelets start their adhesion via vWFs, change their shape and release the content of the granules.Meanwhile, the blood flow to the concerned region decreases, the body respond immediately and a local vasoconstriction occurs to limit the blood loss. Thromboxane A2 and Adenosine diphosphate (ADP) are two important molecules contained in the granules, they promote further aggregation of the platelets and stimulate the contraction of smooth muscles cells surrounding the vessels to cause the regional vasoconstriction.Fibrinogens join the party and bind to more platelets via IIbIIIa receptors, the end result is a local platelet plug, effective for stopping the bleeding temporarily but somehow unstable.

B/coagulation cascade:

The goal of this phase is to form an insoluble and solid blood clot that can stop bleeding for good.This can be achieved through transforming the fibrinogen molecules in fibrin by the enzyme thrombin, there are two pathways for thrombin activation: The extrinsic pathway and the intrinsic pathway, both are composed of many coagulation factors, and share a final pathway.

Clotting factors are precursors of proteolytic enzymes called 'zymogens' that circulate in an inactive form.The activation of each zymogen is described by the suffixing letter “a” to the Roman numeral identifying that particular zymogen.

They are formed in the liver and the majority of their production needs vit K, this is why people with thrombotic disorders receive vit K antagonists as a drug to reduce their hypercoagulability state.

For more info, please check out the table in the third source, it contains all the clotting factors as well as their functions.

1/The intrinsic pathway:

The intrinsic pathway begins with the exposure of the sub-endothelial layer, factor XII is activated and transform the factor XI into its active form XIa.This first step requires high molecular weight kininogen (HMWK), prekallikrein and calcium ion.XIa transforms the IX factor into IXa leading to the formation of the first complex on the platelet membrane capable of activating the X factor.This complex is known as Tenase Complex and it's composed of the external layer of the platelet, the IXa factor, the Antihemophilic factor A (factor VIII) and calcium ion just as shown above.

2/The extrinsic pathway:

This pathway is simpler than the last one, in fact, the sub-endothelium contains Tissue Factor (TF) or factor III capable of activating the VII factor, it's a glycoprotein found the sub-endothelial layers.The extrinsic pathway is the main pathway of coagulation in vivo, the intrinsic pathway potentialized the actions of the cascade even further, in reality, they work in synergy.The final result 'VIIa' is capable of activating the X factor.

3/The Common Pathway:

The two previous pathways lead to the activation of the X factor to Xa which binds to the phospholipids bilayer found in the platelet's membrane and forms with the presence of Va the prothrombinase complex.It's complex formed by Xa, Va, phospholipids and calcium ion.Its main action is the transformation of prothrombin (inactive form) to thrombin (which is the point of this whole crap is the first place ! ).Now you probably wonder where does Va come from? In the blood, the enzyme thrombin is found in very small quantities and it's able to activate the V factor into Va.After the formation of prothrombinase complex, the transformation of prothrombin to thrombin skyrockets exponentially! Now thrombin takes action and transforms fibrinogen into fibrin.Not forgetting to mention the XIII factor which is a stabilizing factor of the fibrin chains activated by the prothrombinase complex.Now we have an insoluble and solid blood clot, cool isn't it?

If you don't think so, just look at this pic of a blood clot taken by an inverted fluorescent confocal microscope,

The green objects are platelets and the red fluorescent staining are fibrin chains.

C/Fibrinolysis:

This is the last step of hemostasis, it's derived from Fibrin and lysis=destruction.Once the clotting begins, it never stops, that's why in the blood there are substances known as anticoagulants, their main action is to stop the clotting cascade.Antithrombin is an important anticoagulant, it reduces the action of thrombin and Xa clotting factor, other anticoagulants include protein C and protein S.

Besides, the process of blood clot formation isn't perfect, sometimes there's an excess of fibrin chains that can reduce the diameter of vessel's lumen or even worse block it completely leading to ischemia and cell death.

Ischemia is a restriction in blood supply to tissues, causing a shortage of oxygen that is needed for cellular metabolism

That's pretty bad! we don't want this to happen, luckily for us, the body has its own mechanisms. Plasminogen is a form of an enzyme (inactive) produced by the liver that can be converted to plasmin by several factors. Plasmin is our rockstar, it cleaves fibrin chains and dissolves the clot.The waste products are called fibrin degradation products (FDPs) and they can be detected clinically to diagnose pathological blood clotting.

Hemostasis is pretty awesome and keeps the body in harmony, coagulation and fibrinolysis work together to ensure the continuity of blood vessels and if any abnormality affects these pathways, we may experience severe bleeding or thrombosis.Now after we understood the basics of hemostasis let's get into the innovation.

The problem with internal bleedings:

As I mentioned before, many internal bleedings go undiagnosed.Generally, if doctors suspect an internal bleeding, a surgical intervention is needed immediately, drugs are useless most of the times.With surgical intervention comes different types of preparations and analysis, not to mention preparing the operation room and all the necessary instruments.Besides, if you watched any medical show, you will know that surgeons don't always know the exact location of the bleeding which is surprisingly accurate (at least this time :p), this ignorance comes from either a shortage of materials (in poor countries) or lack of time. In every different scenario, the process takes time and 'time=chance to survive' especially if the victim suffers a severe blood loss or it took a while to get him to the hospital.So there's no surprise that many victims die from internal bleedings even before attending the operating room.

Basics of the technique:

Nanotechnology is manipulation of matter on an atomic, molecular, and supramolecular scale

Nanoparticles technology was presented recently in medical field, the major encountered problems were essentially due to the high toxicity and cost of certain elements.only two materials were approved for injections, Aluminum oxide, and Iron oxide.

Researchers at the University of ITMO In Saint Petersburg Russia managed to create pure and highly stable nanoparticles in aqueous media (in our case it's the blood) made of magnetite.

In case you don't know ...

Magnetite is a rock mineral and one of the main iron ores.Its chemical formula is 'Fe3O4', it is one of the oxides of iron.

Magnetite is known for super-magnetic abilities which's the reason for its uses in the first place, take a look at a magnetite rock found in Russia, just wonderful!

But that's not even the beauty of the thing! They were able to put biological molecules in these nanoparticles, they can be enzymes, hormones, etc.As we've seen above, thrombin is the key enzyme of blood clotting, the whole point of intrinsic and extrinsic pathways is thrombin activation.

The researchers were able to trap thrombin molecules inside forming [email protected] nanoparticles, although they noticed a decreased activity of these molecules, Andrey Drozdov a member of the team who developed this technique said:

It turned out that magnetic localization compensates for lower activity. Nanoparticles reduce the clotting time by 6.5 times and can reduce total blood loss by 15 times.

Now if you wonder how we can use in medical facilities, it's quite simple!

First, we need to locate the bleeding using a common imaging technique like Angiography for example (blood vessels imaging) or CT scans.Next, we inject these particles into the veins of the patient, use a magnet to attract them to the wanted site and the magic begins!

Conclusion:

The technique is still new and we still need further tests but it's very very promising! If it becomes available in clinics and hospitals, many lives will be saved.We've really achieved a lot of progress in the medical field, the life expectancy is increased dramatically last decade, so be aware immortality here we come!

Thank you very much for taking the time to read my article, please if you have any thought about the subject make sure to share it!

If you want more, here are some of my old articles:

I wish you all good day ^^

References & Sources:

Hemostasis 1

Hemostasis 2

Coagulation

Fibrinolysis

Magnetite

Hemostatic magnetically-driven nanoparticles 1

Hemostatic magnetically-driven nanoparticles 2

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