What do Anticoagulants do?

There are several groups of anticoagulants, and each has a different mechanism of action! Some of the most commonly used are drugs such as heparin and coumarin.

This group of medications is usually administered to patients with myocardial infarction, venous thrombosis, peripheral arterial emboli and pulmonary emboli. Therefore, anticoagulants are not only extremely useful, but lifesaving because they are used to prevent transient ischemic attacks and to reduce the risk of recurrent myocardial infarction.

Overview of coagulation

Coagulation, also known as blood clotting, is a complex physiological process that prevents excessive bleeding when blood vessels are injured. It involves a series of tightly regulated reactions that lead to the formation of a stable blood clot at the site of injury. When a blood vessel is damaged, the body initiates vasoconstriction, a process in which the blood vessel narrows to reduce blood flow to the injured area, minimizing blood loss.

Platelets, small cell fragments in the blood, play a crucial role in coagulation. Upon vessel injury, platelets adhere to the exposed collagen at the injury site, triggering platelet activation. This causes the platelets to change shape and release chemical signals that attract more platelets to the injured area, forming a temporary platelet plug that further reduces blood loss.

The coagulation cascade, a series of enzymatic reactions involving various clotting factors, takes place next. The cascade is divided into intrinsic and extrinsic pathways, which eventually merge into a common pathway. These pathways activate proenzymes, converting them into active enzymes that catalyze the conversion of soluble fibrinogen into insoluble fibrin.

The final step of coagulation involves the conversion of fibrinogen, a soluble plasma protein, into fibrin, an insoluble protein. Fibrin forms a mesh-like network that traps red blood cells, platelets, and other components, strengthening the platelet plug and stabilizing the blood clot.

After serving its purpose of preventing bleeding, the clot undergoes clot retraction, where its edges contract, pulling the wound edges closer together. Over time, the clot is dissolved by fibrinolysis, a process involving the enzyme plasmin, which breaks down fibrin into smaller fragments, eventually restoring blood flow.

Mechanism of clotting

A blood clot forms as a result of concerted action of some 20 different substances, mostly plasma glycoproteins. This extremely complex process can be divided into two different pathways, although their end result is the same:

• the intrinsic pathway
• the extrinsic pathway

The difference between these two pathways is in the composition of the proteins and their origin. The intrinsic pathway uses only factors that are soluble in plasma, while the extrinsic pathway consists of some factors that are insoluble in plasma.

Both pathways, after the initiation of coagulation, proceed through a common pathway by forming activated factor X. Factor II or Prothrombin is cleaved at two sites by factor Xa to yield thrombin which directly cleaves fibrinogen.  There is a lot of fibrinogen in the blood, 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 a more stable "hard clot" by the covalent cross-linking of neighboring fibrin molecules.

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

Types of anticoagulants

There are several different types of anticoagulants, and some of the commonly used are:

Heparin and derivative substances

Heparin is frequently used in order to prevent life-threatening clotting in many patients, especially those which have had stent implants on their heart. Unlike some other coagulants, Heparin is a biological substance. Although there are many forms of production, it is usually made from pig intestines. The mechanism of function is rather simple; it activates antithrombin III, a substance in our body that blocks thrombin from clotting blood.

Heparin 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 is called low molecular weight heparin.

Vitamin K antagonists

Also called the common oral anticoagulants, these represent a form of anticoagulants which act by blocking the effects of vitamin K (which promotes coagulation). They take 48-72 hours to develop to full effect, which is why they shouldn’t be used when immediate effect is required. In these cases, it’s 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!

The most common complication is of course unstoppable bleeding, especially in patients aged 80 or more.

Oral Coagulants

The most important oral anticoagulants are: Warfarin (Coumadin® ), Acenocoumarol, Phenprocoumon, and Phenindione.

Direct thrombin inhibitors

Some of the most commonly used medications from this group are  Argatroban, Lepirudin, and Bivalirudin.

There was a minor affair with one medication from this group – an oral direct thrombin inhibitor called Ximelagatran (Exanta®). It has been proven that it can cause severe liver damage and heart attacks. It was denied approval by the FDA in September 2004.

Cofactors

Various different substances are required for the proper functioning of the coagulation cascade. They are usually called cofactors, and the most important are Vitamin K, Calcium and phospholipid.

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

Vitamin K is an essential factor to a hepatic gamma-glutamyl carboxylase, an especially important liver enzyme which 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

Our blood is normally filled with anticoagulants but – are there any outside of the body? Although we don’t think about it, all laboratory instruments, test tubes, blood transfusion bags, and medical and surgical equipment is covered with anticoagulants. If there was no anticoagulant on them, they would get clogged up and become non-operational.

Beside heparin, most commonly used anticoagulants are:

• EDTA - one of the most commonly used types; it can be normally found on purple caps on Vacutainer brand test tubes. It works by binding Ca-ions.
• Citrate: This anticoagulant is also normally found on blue Vacutainer tubes. It exists in liquid form, which makes it suitable for coagulation tests. 
• Hirudin: This is a naturally occurring anticoagulant found in the saliva of leeches. Synthetic versions of hirudin have been used in medical devices and procedures to prevent blood clotting.
• Bivalirudin: Bivalirudin is a synthetic anticoagulant used during certain medical procedures, such as percutaneous coronary interventions (PCI) or angioplasty, to prevent clot formation in the catheters and blood vessels.