What do Anticoagulants do?

One extremely useful group of substances and medications are called the anticoagulants! What they really are? Well, according to the medical definition- they represent all possible compounds that do not allow blood to clot. There are several groups of anticoagulants and they have different mechanisms of action! Some of the most commonly used medications are drugs such as heparin and coumarin.  It is important to point out that this group of medications is usually administered to patients with myocardial infarction, venous thrombosis, peripheral arterial emboli and pulmonary emboli. Therefore, they are not only extremely useful, but life saving because they have also been used to prevent transient ischemic attacks and to reduce the risk of recurrent myocardial infarction.

Overview of coagulation

What exactly is coagulation? Well, it is one extremely complex process and to explain all process of it- it could take days! The simplest definition is that coagulation is a complex process by which blood forms solid clots. It is part of one much more biger process called the hemostasis, which represent preventing over bleeding and death!  That’s why it is logical that disorders of coagulation can lead to an increased risk of bleeding, clotting, embolism and death! Therefore it represents a vital process!

It is also important to know that coagulation is extremely fast process which means that it is initiated almost instantly after an injury to the blood vessel’s endothelium. Hemostasis can be primary and secondary! Primary is done by hemostatic plug at the site of injury and the secondary hemostasis occurs simultaneously—via coagulation factors which form fibrin.

Mechanism of clotting

      Like we have already mentioned that a blood clot forms as a result of concerted action of some 20 different substances. Most of these substances are plasma glycoproteins. This extremely complex process can be divided into two different pathways although the result is the same! These pathways are:

·        the intrinsic pathway

·        the extrinsic pathway

What is the difference between these two pathways? Well, the difference is in the composition of the proteins and their origin! You see, the intrinsic pathway uses only factors that are soluble in the plasma, while the extrinsic pathway consists of some factors that are insoluble in the plasma. Although there are even more differences- the fact is that  this part of the coagulation is still unknown!

Common thing for both pathways is that they both, after the initiations of coagulation- proceed through a common pathway by forming activated factor X.

It is also important to know that factor II or Prothrombin is cleaved at two sites by factor Xa to yied thrombin. What should we know about thrombin! Well, it is important factors because it directly cleaves fibrinogen.  There is a lot of fibrinogen in the blood! Experts are saying that it could be about 2-3% of plasma protein. Thrombin is important because it chemically changes arg-X peptide bond in fibrinogen to form soluble fibrin monomers. These monomers are the key of coagulation because they spontaneously aggregate to form a polymeric structure called "soft clot" which later turns into one more stable "hard clot" by the covalent cross-linking of neighboring fibrin molecules.

Below are listed most of the blood coagulation factors along with their most important function in the chain of coagulation:

Types of anticoagulants

Like we already know anticoagulants are one specific type of medications which are usually given to people to stop thrombosis. Thrombosis is one extremely serious and sometimes life-threatening process which is characterized by inappropriate clotting of blood in the blood vessels.  That’s why- these anticoagulants are sometimes irreplaceable form of treatment, especially in certain conditions such as primary and secondary prevention of deep vein thrombosis, pulmonary embolism, myocardial infarctions and strokes. They could be used in acute conditions as well as the part of prophylaxis.

There are several types of anticoagulants and some of most commonly used are:

Heparin and derivative substances

Almost everyone has heard about Heparin because it is extremely frequently used in order to prevent life-threatening clotting in many patients, especially those which have had the stent implants on their heart! We should know that, unlike some other coagulants- Heparin is a biological substance. Although there are many forms of production- it is usually made from pig intestines. How this Heparin work? Well, the mechanism of work is rather simple because it activates antithrombin III, one specific substance in our body that blocks thrombin from clotting blood. It can be administrated by injection, or in vitro to prevent blood or plasma clotting in or on medical devices.  There are several forms of Heparin and the most commonly used form is called the low molecular weight heparin!   

Vitamin K antagonists

Vitamin K antagonists are also called the common oral anticoagulants. These represent a specific form of anticoagulants which act by blocking the effects of vitamin K. Like we already know- vitamin K promotes coagulation! There is one important thing to know about this class of medications - they take at least 48 to 72 hours to develop fully effect. This is why- they shouldn’t be used when the immediate effect is required! In these cases- it is best to use heparin. Most common indications for this type of anticoagulants are deep-vein thrombosis (DVT), pulmonary embolism, atrial fibrillation, and mechanical prosthetic heart valves such as stents and different dilatators!

Most common side effects

The most common complication is of course- unstoppable bleeding, especially in patient which are aged 80 years or more. Most commonly used

The most important oral anticoagulants are:

·         Warfarin (Coumadin) – far most commonly used!

·          Acenocoumarol and Phenprocoumon  

·         Phenindione

Direct thrombin inhibitors

Beside oral anticoagulants- important type of anticoagulants is the direct thrombin inhibitors. Some of the most commonly used medications from this group are:

·         Argatroban

·         Lepirudin

·         Bivalirudin

There was also one minor affair with one medication from this group-an oral direct thrombin inhibitor called Ximelagatran (Exanta®).

Cofactors

The fact is also that various different substances are required for the proper functioning of the coagulation cascade. They are usually called the cofactors and the most important are Vitamin K, Calcium and phospholipid!  

·         Calcium and phospholipid

These substances are required for the several complexes to function, especially tenase and prothrombinase.  Not only that- Calcium is also required at other points in the coagulation cascade.

·         Vitamin K

This vitamin is an essential factor to a hepatic gamma-glutamyl carboxylase, especially important liver enzyme. Why is this enzyme so important? Well, it adds a carboxyl group to residues on factors II, VII, IX and X, as well as Protein S, Protein C and Protein Z. 

Anticoagulants outside the body

We have already pointed out that our blood is normally filled with anticoagulants but – are there any outside our body? Yes, there are! Although we don’t think about it- the fact is that all laboratory instruments, test tubes, blood transfusion bags, and medical and surgical equipment is covered with these anticoagulants! Why? Well, if there was no anticoagulant on them- they would get clogged up and become nonoperational. Beside the heparin, most commonly used anticoagulants are:   

·         EDTA

EDTA is one of the most commonly used and it can be normally found on purple caps on Vacutainer brand test tubes. It works by binding Ca-ions and therefore- preventing coagulation! 

·         Citrate

This anticoagulant is also normally found on Vacutainer tube, the blue ones! It is also characteristic that this medication is in liquid form which makes it very suitable for coagulation tests.  

• www.wikipedia.com
• www.people.vcu.edu
• http://www.americanheart.org/