coagulants. According to the classification, this group of drugs is divided into direct and indirect coagulants, but sometimes they are divided according to a different principle.

Anticoagulants are a group of drugs that inhibit blood clotting and prevent thrombosis by reducing the formation of fibrin.

Anticoagulants affect the biosynthesis of certain substances that inhibit clotting processes and change blood viscosity.

In medicine, modern anticoagulants are used for preventive and therapeutic purposes. They are available in different forms: in the form of ointments, tablets or solutions for injection.

Only a specialist can choose the right drugs and choose their dosage.

Improperly performed therapy can harm the body and cause serious consequences.

High mortality due to cardiovascular diseases is explained by the formation of blood clots: almost half of those who died from heart disease were found to have thrombosis.

Venous thrombosis and PE are the most common causes of disability and death. Therefore, cardiologists recommend starting to use anticoagulants immediately after the discovery of vascular and heart diseases.

Their early use helps prevent the formation and increase of a blood clot, clogging of blood vessels.

Most anticoagulants do not act on the blood clot itself, but on the blood coagulation system.

After a series of transformations, plasma coagulation factors are suppressed and the production of thrombin, an enzyme required to create fibrin filaments that form a thrombotic clot, occurs. As a result, thrombus formation slows down.

The use of anticoagulants

Anticoagulants are indicated for:

Contraindications and side effects of anticoagulants

Anticoagulants are contraindicated in people suffering from the following diseases:

Bleeding hemorrhoids;
Peptic ulcer of the duodenum and stomach;
Renal and liver failure;
Liver fibrosis and chronic hepatitis;
thrombocytopenic purpura;
Urolithiasis disease;
Deficiency of vitamins C and K;
Cavernous pulmonary tuberculosis;
Pericarditis and endocarditis;
Malignant neoplasms;
Hemorrhagic pancreatitis;
Intracerebral aneurysm;
Myocardial infarction with hypertension;
Leukemia;
Crohn's disease;
Alcoholism;
Hemorrhagic retinopathy.

Anticoagulants should not be taken during menstruation, pregnancy, lactation, in the early postpartum period, the elderly.

Side effects include: symptoms of intoxication and dyspepsia, necrosis, allergies, rash, skin itching, osteoporosis, kidney dysfunction, alopecia.

Complications of therapy - bleeding from internal organs:

Nasopharynx;
Intestines;
Stomach
Hemorrhages in the joints and muscles;
The appearance of blood in the urine.

To prevent the development of dangerous consequences, it is necessary to monitor the patient's condition and monitor blood counts.

Natural anticoagulants

They can be pathological and physiological. Pathological in some diseases appear in the blood. Physiological are normally found in plasma.

Physiological anticoagulants are divided into primary and secondary. The first are independently synthesized by the body and are constantly present in the blood. Secondary appear during the splitting of coagulation factors in the process of formation and dissolution of fibrin.

Primary natural anticoagulants

Classification:

Antithrombins;
Antithromboplastins;
Fibrin self-assembly inhibitors.

With a decrease in the level of primary physiological anticoagulants in the blood, there is a risk of thrombosis.

This group of substances includes the following list:

Secondary physiological anticoagulants

Formed during blood clotting. They also appear during the breakdown of coagulation factors and the dissolution of fibrin clots.

Secondary anticoagulants - what is it:

Antithrombin I, IX;
fibrinopeptides;
Antithromboplastins;
PDF products;
Metafactors Va, XIa.

Pathological anticoagulants

With the development of a number of diseases, strong immune coagulation inhibitors can accumulate in plasma, which are specific antibodies, like lupus anticoagulant.

These antibodies indicate a specific factor, they can be produced to combat the manifestations of blood clotting, but according to statistics, these are inhibitors of factor VII, IX.

Sometimes, with a number of autoimmune processes in the blood and paraproteinemias, pathological proteins with antithrombin or inhibitory effects can accumulate.

The mechanism of action of anticoagulants

These are drugs that affect blood clotting, are used to reduce the risk of blood clots.

Due to the formation of a blockage in organs or vessels, the following may develop:

Gangrene of the limbs;
Ischemic stroke;
thrombophlebitis;
ischemia of the heart;
Inflammation of blood vessels;
Atherosclerosis.

According to the mechanism of action, anticoagulants are divided into drugs of direct / indirect action:

"Direct"

Act directly on thrombin, lowering its activity. These drugs are prothrombin deactivators, thrombin inhibitors and inhibit thrombus formation. In order to prevent internal bleeding, it is necessary to control the parameters of the coagulation system.

Direct anticoagulants quickly enter the body, are absorbed in the gastrointestinal tract and reach the liver, have a therapeutic effect and are excreted in the urine.

They are divided into the following groups:

Heparins;
Low molecular weight heparin;
Hirudin;
sodium hydrocitrate;
Lepirudin, danaparoid.

Heparin

The most common anti-clotting agent is Heparin. It is a direct acting anticoagulant drug.

It is administered intravenously, intramuscularly and under the skin, and is also used as an ointment as a topical remedy.

Heparins include:

Adreparin;
Nadroparin sodium;
Parnaparin;
Dalteparin;
Tinzaparin;
Enoxaparin;
Reviparin.

Antithrombotic drugs of local action have not very high efficiency and insignificant permeability in the tissue. Used to treat hemorrhoids, varicose veins, bruises.

The most commonly used with heparin are the following:

Heparins for subcutaneous and intravenous administration are drugs that reduce clotting, which are individually selected and are not replaced by one another during treatment, since they are not equivalent in effect.

The activity of these drugs reaches a maximum after about 3 hours, and the duration of action is a day. These heparins block thrombin, reduce the activity of plasma and tissue factors, prevent the formation of fibrin filaments, and prevent platelet aggregation.

For the treatment of angina, heart attack, pulmonary embolism and deep vein thrombosis, Deltaparin, Enoxaparin, Nadroparin are usually prescribed.

For the prevention of thrombosis and thromboembolism, Reviparin and Heparin are prescribed.

sodium hydrocitrate

This anticoagulant is used in laboratory practice. It is added to test tubes to prevent blood clotting. It is used to preserve blood and its components.

"Indirect"

They affect the biosynthesis of side enzymes of the coagulation system. They do not suppress the activity of thrombin, but completely destroy it.

In addition to the anticoagulant effect, the drugs of this group have a relaxing effect on smooth muscles, stimulate the blood supply to the myocardium, remove urates from the body and have a hypocholesterolemic effect.

"Indirect" anticoagulants are prescribed for the treatment and prevention of thrombosis. They are used exclusively inside. The form of tablets is used for a long time in an outpatient setting. Abrupt withdrawal leads to an increase in prothrombin and thrombosis.

These include:

Substances	Description
Coumarin	Coumarin is naturally found in plants (melilot, bison) in the form of sugars. In the treatment of thrombosis, dicoumarin, its derivative isolated from clover in the 1920s, was first used.
Indan-1,3-dione derivatives	Representative - Fenilin. This oral drug is available in tablets. The action begins 8 hours after ingestion, and the maximum effectiveness occurs a day later. When taking, it is necessary to check the urine for the presence of blood, as well as to control the prothrombin index.

"Indirect" drugs include:

neodicumarin;
Warfarin;
Acenocoumarol.

Warfarin (thrombin inhibitors) should not be taken in certain diseases of the liver and kidneys, thrombocytopenia, with a tendency to bleeding and acute bleeding, during pregnancy, with DIC, congenital deficiency of proteins S and C, lactase deficiency, if the absorption of glucose and galactose is impaired.

Side effects include nausea, vomiting, abdominal pain, diarrhea, bleeding, nephritis, alopecia, urolithiasis, allergies. There may be itching, skin rash, vasculitis, eczema.

The main disadvantage of Warfarin is an increased risk of bleeding (nasal, gastrointestinal, and others).

New generation oral anticoagulants (NOACs)

Anticoagulants are indispensable drugs used in the treatment of many pathologies, such as thrombosis, arrhythmias, heart attacks, ischemia, and others.

However, drugs that have proven effective have many side effects.. Development continues, and new anticoagulants occasionally appear on the market.

Scientists are trying to develop universal remedies that are effective in various diseases. Drugs are being developed for children and patients for whom they are contraindicated.

New generation blood thinners have the following advantages:

The action of the drug comes on and off quickly;
When taken, the risk of bleeding is reduced;
The drugs are indicated for patients who cannot take Warfarin;
The inhibition of thrombin-related factor and thrombin is reversible;
The influence of food consumed, as well as other drugs, is reduced.

However, the new drugs also have disadvantages:

Must be taken regularly, while older remedies can be skipped due to long-term effect;
Lots of tests
Intolerance by some patients who could take old pills without side effects;
Risk of bleeding in the gastrointestinal tract.

The list of new generation drugs is small.

The new drugs Rivaroxaban, Apixaban and Dabigatran may be alternatives for atrial fibrillation. Their advantage is the absence of the need to constantly donate blood during the reception, they do not interact with other drugs.

However, NOACs are just as effective if the risk of bleeding is not higher.

Antiplatelet agents

They also help thin the blood, but they have a different mechanism of action: antiplatelet agents prevent platelets from sticking together. They are prescribed to enhance the effect of anticoagulants. In addition, they have a vasodilating and antispasmodic effect.

The most famous antiplatelet agents:

Aspirin is the most commonly used antiplatelet agent. An effective agent that thins the blood, dilates blood vessels and prevents thrombosis;
Tirofiban - interferes with the adhesion of platelets;
Eptifibatite - inhibits platelet aggregation;
Dipyridamole is a vasodilator;
Ticlopidin - used for heart attacks, cardiac ischemia and in the prevention of thrombosis.

The new generation includes Brilint with the substance ticagrelor. It is a reversible P2U receptor antagonist.

Conclusion

Anticoagulants are indispensable drugs in the treatment of pathologies of the heart and blood vessels. They cannot be taken on their own.

Anticoagulants have many side effects and contraindications, and uncontrolled intake can cause bleeding, including hidden ones. The appointment and calculation of the dosage are performed by the attending physician, who can take into account all the possible risks and features of the course of the disease.

During treatment, regular laboratory monitoring is required.

It is very important not to confuse anticoagulants and antiplatelet agents with thrombolytic agents. The difference lies in the fact that anticoagulants do not destroy the thrombus, but only slow down or prevent its development.

Anticoagulant drugs inhibit the activity of the blood coagulation system, preventing the formation of new blood clots, or destroying existing ones. This group of medicines is widely used in all branches of medicine.

Thanks to such drugs in surgical patients, mortality in the postoperative period has significantly decreased.

Anticoagulants are substances or drugs that inhibit the activity of the blood coagulation system, and also prevent the formation of blood clots.

Preparations of this series used in all areas of medicine. However, anticoagulants are most widely used in cardiology and surgery. In the course of any, even minor, surgical interventions, the integrity of body tissues is violated. In this case, the hemostasis system is activated, which is characterized by increased thrombus formation.

Lack of correction of this condition can lead to the development of acute disorders of cerebral and coronary circulation, as well as thromboembolism of the branches of the pulmonary artery.

That is why it is extremely important to carry out adequate anticoagulant therapy in the postoperative period.

In cardiological practice, the use of anticoagulants becomes especially important in the post-infarction period, with arrhythmias, as well as heart failure.

Anticoagulants are prescribed for life to patients who have undergone stenting or coronary artery bypass grafting.

Natural anticoagulants

To understand what anticoagulants are, you can only understand the mechanism of action of these substances. In the human body, there are both clotting and anti-clotting systems. The former are responsible for formation of thrombotic masses in violation of the integrity of vascular structures. The latter prevent excessive activity of the blood coagulation system, and are also responsible for the timely splitting of existing blood clots.

Natural anticoagulants are divided into primary and secondary. Primary factors constantly circulate in the vascular bed and prevent the uncontrolled formation of blood clots. They are also divided into several subcategories.

Fibrin creation inhibitors- prevent the conversion of fibrinogen to fibrin.
Antithromboplasty substances have an antiprothrobinase effect.
Antithrombins structures that bind thrombin.

A decrease in the activity of these substances causes the development of thrombosis, and is also one of the key factors in the appearance of DIC.

Primary blood anticoagulants are:

antithrombin III;
alpha2-antiplasmin;
heparin;
alpha macroglobulin;
apolyprotein A-11;
alpha2 antitrypsin;
placental anticoagulant - produced only when the placenta is formed;
C1-esterase inhibitor;
LAKI - Lipoprotein-associated coagulation inhibitor;
proteins S and C;
autoantibodies produced to active coagulation factors;
fibrin assembly inhibitor;
thrombomodulin;
glycoproteins.

Secondary factors are formed in the process of destruction of blood clots:

fibrin peptides;
antithrombin I;
metafactors - Va, Xia;
PDF - degradation products of fibrin, as well as fibrinogen;
degradation products of prothrombins Q, P, R.

Despite the variety of natural blood factors, the balance between the coagulation and anticoagulation systems is not always achieved. Insufficient activity of natural anticoagulants and excessive activity of the blood coagulation system can lead to increased thrombosis. In this case, there is a need for the use of anticoagulant drugs.

Anticoagulants

Modern anticoagulants allow you to influence the blood coagulation system, lowering its activity.

This leads to a decrease in blood viscosity and the likelihood of blood clots.

The mechanism of action of anticoagulants depends on the class of drugs to which they belong..

For a better understanding, classifications have been created that indicate the points of action of specific groups of drugs.

Classification

Classification of anticoagulants begins with separation of drugs according to the mechanism of action. There are drugs that act directly on blood coagulation factors - they are also called direct.

Indirect drugs include drugs that affect the metabolic processes of the liver, reducing the synthesis of vitamin K. The latter is an important factor in the conversion of prothrombin to thrombin (platelet hemostasis).

There are main classes among anticoagulants of direct action and indirect action:

Heparins- Antithrombin III, Sulodexide, Enoxiparin.
Vitamin K antagonists- Warfarin, Acenocoumarol, Phenindione.
Thrombolytics- Streptokinase, Fibrinolysin, Tenecteplase, Alteplase, Urokinase, Protein C, Ancord.
Direct factor Xa inhibitors- Darexaban, Rivaroxaba, Apixaban, Betrixaban, Endoxaban.
Antiplatelet agents- Clopidogrel, acetylsalicylic acid, Indobufen, Ticagrelor, Dipyridamod, Abciximab, Ticlopidin.
Direct thrombin inhibitors- Bivalirudin, Lepirudin, Dabigatran, Ximelanatran, Desirudin, Melanatran, Argatroban.
Other antithrombotic agents- Fondaparinux, defibrotide, dermatan sulfate.

Many patients with a history of atrial fibrillation, ischemia or myocardial infarction, transient ischemic attack of the brain, prefer to carry an anticoagulant tablet that can be drunk quickly.

For those people who are at high risk of developing cardiovascular events, better to ask your doctor what are these new oral anticoagulants, and which one is better to always have with you. The drug may differ (depending on the patient's medical condition). Usually it is Dabigatran, Apixaban, eparin.

Direct acting drugs

In turn, direct-acting drugs are divided into the following subcategories:

heparins, as well as their derivatives;
low molecular weight heparins;
sodium hydrocitrate;
danaparoid, as well as lepirudin;
hirudin.

Indirect drugs

The list of anticoagulant drugs with an indirect mechanism of action can also be divided into subcategories:

dicoumarins;
monocoumarins (obtained from oxcoumarin);
indandiones.

Coumarin anticoagulants have been used in medicine since the 1940s. At the moment they are not as widespread as other groups, however widely used in cardiology.

In particular, Warfarin is a key drug in the treatment of atrial fibrillation. It prevents the formation of blood clots in the right ear of the heart and reduces the risk of adverse cardiovascular complications.

Indadiones are less widely used in medical practice.

Indications for use

You can understand what anticoagulants are in medicine, knowing the indications for the use of these drugs. There is a list of situations in which the use of anticoagulants is mandatory.

postoperative period.
Conditions after acute cerebrovascular accident.
Postponed myocardial infarction.
branches of the pulmonary artery.
Atrial fibrillation.
, and .
Obliterating endarteritis.

Violations of the normal rhythm of the heart contributes to increased thrombosis, and significantly increases the risk of stroke, heart attack, pulmonary embolism. Therefore, the cardiologist necessarily prescribes a certain list of anticoagulant drugs. with arrhythmias, the use of which reduces the risk of developing these complications.

The choice of group and drug depends on the state of health of a particular patient, his pathology and the state of the blood coagulation system. For this, there is a coagulogram that displays the functional activity of the blood system before, during and after the use of drugs.

Any doctor can prescribe anticoagulant drugs if he sees a risk of developing thrombotic complications. The most common cases are listed above. However, in other branches of medicine, these drugs can be prescribed.

Contraindications

Any anticoagulant used with caution in women during pregnancy. These drugs can only be used under the control of a coagulogram and in situations where the risk of undesirable consequences for the mother and child is higher than from possible side effects.

There are other contraindications to anticoagulants, which include:

Prescribe anticoagulants with caution and with infectious diseases.

natural remedies

Some foods also have anticoagulant activity.

Large volumes of liquid - water, compote, tea.
Cucumbers.
Watermelon.
Flaxseed oil and lean fish.
Oatmeal.
Cranberry drinks from other dark berries.
Iodine-containing foods - seaweed.
Grape drinks.

Unfortunately, the use of these products does not allow you to fully maintain the hemostasis system at an appropriate level.

However, such properties must be remembered by people who take anticoagulant drugs - Excess consumption of them can cause internal and external bleeding..

Conclusion

There are clear indications and contraindications for the appointment of antithrombotic drugs. They should be taken only as prescribed by the attending physician under the strict control of the coagulogram.

Despite the existing contraindications and possible side effects, you should not be afraid of taking these medicines. Their use can prevent the development of serious complications and even save a person's life.

1. Coagulants (agents that stimulate the formation of fibrin thrombi):

a) direct action (thrombin, fibrinogen);

b) indirect action (vikasol, phytomenadione).

2. Fibrinolysis inhibitors:

a) synthetic origin (aminocaproic and tranexamic acids, amben);

b) animal origin (aprotinin, contrykal, pantrypin, Gordox "Gedeon

Richter, Hungary);

3. Stimulants of platelet aggregation (serotonin adipate, calcium chloride).

4. Means that reduce vascular permeability:

a) synthetic (adroxon, etamsylate, iprazochrome); b) vitamin preparations (ascorbic acid, rutin, quercetin).

c) herbal preparations (nettle, yarrow, viburnum, water pepper, arnica, etc.)

II. Anti-clotting agents or antithrombotic agents:

1. Anticoagulants:

a) direct action (heparin and its preparations, hirudin, sodium citrate, antithrombin III);

b) indirect action (neodicoumarin, syncumar, phenylin, fepromarone).

2. Fibrinolytics:

a) direct action (fibrinolysin or plasmin);

b) indirect (plasminogen activators) action (streptolyase, streptokinase, urokinase, actilyse).

3. Antiplatelet agents:

a) platelets (acetylsalicylic acid, dipyridamole, pentoxifylline, ticlopidine, indobufen);

b) erythrocyte (pentoxifylline, reopoliglyukin, reogluman, Rondex).

Means that increase blood clotting (hemostatics) coagulants

According to the classification, this group of drugs is divided into direct and indirect coagulants, but sometimes they are divided according to a different principle:

1) for local use (thrombin, hemostatic sponge, fibrin film, etc.)

2) for systemic use (fibrinogen, vikasol).

THROMBIN (Trombinum; dry powder in amp. o, 1, which corresponds to 125 units of activity; in vials of 10 ml) is a direct-acting coagulant for topical use. Being a natural component of the blood coagulation system, it causes an effect in vitro and in vivo.

Before use, the powder is dissolved in saline. Usually the powder in the ampoule is a mixture of thromboplastin, calcium and prothrombin.

Apply only locally. Assign to patients with bleeding from small vessels and parenchymal organs (surgery on the liver, kidneys, lungs, brain), bleeding from the gums. It is used topically in the form of a hemostatic sponge soaked in thrombin solution, a hemostatic collagen sponge, or simply by applying a swab soaked in thrombin solution.

Sometimes, especially in pediatrics, thrombin is used orally (the contents of the ampoule are dissolved in 50 ml of sodium chloride or 50 ml of 5% amben solution, 1 tablespoon is prescribed 2-3 times a day) for gastric bleeding or by inhalation for bleeding from the respiratory tract.

FIBRINOGEN (Fibrinogenum; in vials of 1.0 and 2.0 dry porous mass) - used for systemic exposure. It is also obtained from the blood plasma of donors. Under the influence of thrombin, fibrinogen is converted into fibrin, which forms blood clots.

Fibrinogen is used as an ambulance. It is especially effective when its deficiency is observed in massive bleeding (placental abruption, hypo- and afibrinogenemia, in surgical, obstetric, gynecological and oncological practice).

Assign usually in a vein, sometimes locally in the form of a film applied to the bleeding surface.

Before use, the drug is dissolved in 250 or 500 ml of warm water for injection. Intravenously administered drip or slowly jet.

VIKASOL (Vicasolum; in tabs, 0.015 and in amp. 1 ml of 1% solution) is an indirect coagulant, a synthetic water-soluble analogue of vitamin K, which activates the formation of fibrin thrombi. Referred to as vitamin K3. The pharmacological effect is caused not by vikasol itself, but by the vitamins K1 and K2 formed from it, so the effect develops after 12-24 hours, with intravenous administration - after 30 minutes, with intramuscular injection - after 2-3 hours.

These vitamins are necessary for the synthesis in the liver of prothrombin (factor II), proconvertin (factor VII), as well as factors IX and X.

Indications for use: with an excessive decrease in the prothrombin index, with severe K-vitamin deficiency due to:

1) bleeding from parenchymal organs;

2) exchange transfusion procedure, if canned blood was transfused (to the child);

and also when:

3) long-term use of vitamin K antagonists - aspirin and NSAIDs (which disrupt platelet aggregation);

4) long-term use of broad-spectrum antibiotics (levomycetin, ampicillin, tetracycline, aminoglycosides, fluoroquinolones);

5) the use of sulfonamides;

6) prevention of hemorrhagic disease of newborns;

7) prolonged diarrhea in children;

8) cystic fibrosis;

9) in pregnant women, especially those suffering from tuberculosis and epilepsy and receiving appropriate treatment;

10) overdose of indirect anticoagulants;

11) jaundice, hepatitis, as well as after injuries, bleeding (hemorrhoids, ulcers, radiation sickness);

12) preparation for surgery and in the postoperative period.

The effects can be weakened by the simultaneous administration of vikasol antagonists: aspirin, NSAIDs, PASK, indirect anticoagulants of the neodicoumarin group.

Side effects: hemolysis of erythrocytes when administered intravenously.

PHYTOMENADION (Phytomenadinum; 1 ml for intravenous administration, as well as capsules containing 0.1 ml of a 10% oil solution, which corresponds to 0.01 of the drug). Unlike natural vitamin K1 (trans compounds) is a synthetic drug. It represents a racemic form (a mixture of trans- and cis-isomers), and in terms of biological activity it retains all the properties of vitamin K1. It is rapidly absorbed and maintains a peak concentration of up to eight hours.

Indications for use: hemorrhagic syndrome with hypoprothrombinemia caused by a decrease in liver function (hepatitis, liver cirrhosis), with ulcerative colitis, with an overdose of anticoagulants, with prolonged use of high doses of broad-spectrum antibiotics and sulfonamides; before major operations to reduce bleeding.

Side effects: phenomena of hypercoagulability in case of non-compliance with the dosing regimen.

Of the drugs related to direct-acting coagulants, the following drugs are also used in the clinic:

1) prothrombin complex (VI, VII, IX, X factors);

2) antihemophilic globulin (VIII factor).

In medical practice, anticoagulant therapy is intended for the prevention of thrombosis and the treatment of pathologies of the heart and vascular system. They produce medicines in the form of creams, gels, ointments, capsules, injection solutions, in tablets. It is strictly forbidden to select a dose on your own, as this can provoke severe bleeding.

Impact

Thrombosis is a dangerous and common condition that often leads to heart attacks, strokes, heart attacks, and death. Disability in these conditions is inevitable. Therefore, doctors prescribe anticoagulant therapy to their patients with clotting problems in advance.

Thanks to early treatment, it is possible to prevent the formation and increase of blood clots, as well as blockage of blood vessels. Usually, anticoagulants act in a complex way, affecting not only the thrombus itself, but also clotting in general.

Anticoagulant therapy consists in the suppression of plasma coagulation factors and the synthesis of thrombin. It is due to thrombin that fibrin filaments and thrombotic clots are formed.

Classification

Anticoagulant substances are classified into the following groups:

pathological and physiological anticoagulants;
indirect anticoagulants;
direct anticoagulant components;
new oral anticoagulants (NOACs);
antiplatelet agents.

Modern anticoagulants, in turn, are divided into direct anticoagulants and indirect anticoagulants.

Pathological components

Formed in the blood in pathologies. These are strong immune coagulation inhibitors, which are specific antibodies that affect certain factors. As a rule, such antibodies are synthesized by the body in order to protect it from manifestations of blood clotting.

Physiological Components

Normally found in the blood. They are usually divided into two types:

secondary;
primary.

This group includes the following list of substances:

Heparin;
Antithrombin III;
Protein C;
Complement-I inhibitor;
Alpha2 macroglobulin;
Protein S;
Lipid and contact inhibitors;
Antithromboplastins.

Heparin is a polysaccharide synthesized in mast cells. Studies have shown large amounts of heparin in the liver and lungs. The use of large doses of the component suppresses platelets and leads to obstruction of blood clotting. As a result, bleeding from the internal organs occurs. Therefore, it is important not to use drugs with heparin on your own without the supervision of a doctor.

Secondary physiological anticoagulants include the following list of drugs:

Antithrombin I, IX;
Antithromboplastins;
PDF products;
fibrinopeptides;
Metafactors Va, XIa.

direct action

Direct anticoagulants have a decrease in thrombin activity, deactivate prothrombin, inhibit thrombin and prevent the emergence of new blood clots. When using direct anticoagulants, it is important to regularly monitor clotting parameters. This is necessary to prevent internal bleeding.

After using direct-acting agents, the therapeutic effect occurs immediately due to the rapid entry of substances into the body. The output is carried out by the kidneys.

This group of funds includes:

Heparin - is able to suppress the adhesion of platelets, accelerating the flow of blood to the heart and kidneys. The drug leads to a decrease in blood pressure, hypocholesterolemic action, increased vascular permeability, suppression of smooth muscle cell proliferation. The substance is indicated for intravenous administration in emergency conditions, as well as subcutaneously - for the prevention of thrombosis. Outwardly, heparin is used for and. The substance is included in such preparations as Heparin ointment and Hepatrombin.
Low molecular weight heparin - has a high antithrombotic activity, bioavailable. The action of low molecular weight heparin is long, the risk of developing hemorrhoidal complications is low. An important difference of this group of drugs is the minimum number of side effects. The introduction is carried out subcutaneously in the lateral surface of the abdomen. Low molecular weight heparins include: Fragmin, Clivarin, Clexane, Fraxiparin, Wessel Due F.
thrombin inhibitors. This group of medicines includes: Hirudin, Girugen, Girulog, Lepirudin.

Indirect action

Anticoagulants of indirect action affect the biosynthesis of side enzymes of the coagulation system. However, they do not suppress the activity of thrombin, but completely destroy it. Also a feature of these medications is their relaxing effect on smooth muscles. Due to this, the blood supply to the heart is stimulated.

Anticoagulants of indirect action are indicated for the therapy and prevention of thrombosis. Reception is carried out exclusively inside for a long time. If drugs are discontinued abruptly, the level of prothrombin rises and the risk increases.

Anticoagulants of indirect action are divided into the following types:

coumarin anticoagulants;
derivatives of indan-1,3-dione.

Based on the classification, indirect anticoagulants, coumarin and Indan-1,3-dione derivatives are as follows:

Phenylin;
neodicumarin;
Warfarin;
Acenocoumarol.

New anticoagulants

New anticoagulants are indicated for use in patients who need to take Warfanin for life. The fact is that Warfarin is an effective, but unpredictable drug. It is important for patients to whom he is prescribed to control the blood 7-10 times a day. If this is not done, the risk of bleeding, which is ultimately difficult to stop, increases significantly.

The modern pharmaceutical industry is looking for ways to solve the problem of warfarin-dependent patients. For this, new anticoagulants are used, which in medicine are referred to as oral anticoagulants.

Oral anticoagulants include:

Xarelto (Rivaroxoban);
Pradaksa (Dabegatran);
Eliquis (Apixaban).

All these drugs are available in two dosage options. In this case, Rivaroxoban must be taken once a day. The rest are used twice a day.

Indications for the use of oral anticoagulants:

atrial fibrillation;
prevention of venous thrombosis;
embolism prevention;
ischemic stroke.

Benefits of oral anticoagulants:

no need to calculate the dose;
there is no need to regularly monitor INR;
oral anticoagulant substances do not interact with food.

Flaws:

must be taken regularly
a lot of research;
risk of stomach bleeding;
intolerance in some patients.

Indications and contraindications

Anticoagulant therapy is indicated for the following conditions:

thrombotic and embolic stroke;
rheumatic heart disease;
thrombophlebitis and acute thrombosis;
the presence of atherosclerotic plaques;
varicose veins and;
aortic aneurysm;
ischemic disease;
TELA;
DIC;
atrial fibrillation.

It is important to note that not everyone is allowed to use anticoagulant drugs. Often substances are forbidden to take:

patients suffering from bleeding hemorrhoids;
patients with stomach and duodenal ulcers;
persons suffering from renal or hepatic insufficiency;
with cavernous tuberculosis;
patients suffering from a deficiency of vitamins C and K;
patients with pancreatitis;
persons suffering from acute form of leukemia;
with alcoholism;
patients suffering from Crohn's disease;
with hemorrhagic retinopathy.

It is important to pay attention to the fact that anticoagulants are forbidden to be used during menstruation, during the period of bearing a child and while breastfeeding. It is also forbidden to take substances after childbirth and the elderly.

Side effects

The phenomena indicated in the reference books include the following list:

nausea;
vomit;
skin rashes;
osteoporosis;
alopecia;
possible complications in the form of bleeding from internal organs.

Antiplatelet agents

They prevent platelets from sticking together, increase the effectiveness of anticoagulants. Antiplatelet agents are able to dilate blood vessels, have an antispasmodic effect.

Antiplatelet agents include:

Aspirin;
Ticlopidin;
Tirofiban;
Dipyridamole.

Aspirin, or Acetyl salicylic acid, is a bright representative of the group. The drug is produced in various dosage forms. The substance is part of a variety of funds. Aspirin is able to suppress platelet aggregation, provoke vasodilation and prevent early formation of blood clots. Previously, Aspirin was widely used to reduce body temperature, now the medicine is highly discouraged for this.

Anticoagulant substances are effective, they are indispensable in the treatment of pathologies of the cardiovascular system. However, it is important not to take them on their own, even the usual Aspirin. People who are used to "prescribing drugs" to themselves often suffer from many side effects. It must be remembered that self-treatment with anticoagulants can lead to irreversible and severe consequences in the form of severe bleeding.

Useful video about anticoagulants

They are divided into natural anticoagulants and synthetic. The former are produced in the body, the latter are produced artificially and are used in medicine as medicines.

Natural

They can be physiological and pathological. Physiological anticoagulants are normally present in plasma. Pathological appear in the blood in some diseases.

Physiological anticoagulants are divided into primary and secondary. The primary ones are synthesized by the body independently and are constantly in the blood. Secondary ones are formed during the splitting of coagulation factors during the formation of fibrin and its dissolution.

Primary natural anticoagulants

They are usually divided into groups:

Antithromboplastins.
Antithrombins.
Fibrin self-assembly inhibitors.

With a decrease in the level of primary physiological anticoagulants in the blood, there is a risk of developing thrombosis.

This group of substances includes:

Heparin. It is a polysaccharide synthesized in mast cells. It is found in significant amounts in the lungs and liver. In large doses, it interferes with the process of blood coagulation at all stages, suppresses a number of platelet functions.
Antithrombin III. Synthesized in the liver, refers to alpha₂-glycoproteins. Reduces the activity of thrombin and some activated coagulation factors, but does not affect non-activated factors. Plasma anticoagulant activity is 75% provided by antithrombin III.
Protein C. It is synthesized by the cells of the liver parenchyma and is in the blood in an inactive form. Activated by thrombin.
Protein S. Synthesized by endothelial cells and liver parenchyma (hepatocytes), depends on vitamin K.
Alpha₂-macroglobulin.
Antithromboplastins.
contact inhibitor.
lipid inhibitor.
Complement-I inhibitor.

Secondary physiological anticoagulants

As already mentioned, they are formed in the process of blood coagulation and dissolution of fibrin clots during the splitting of some coagulation factors, which, due to degradation, lose their coagulative properties and acquire anticoagulant ones. These include:

Antithrombin I.
Antithrombin IX.
Metafactors XIa and Va.
Febrinopeptides.
Auto-II anticoagulant.
Antithromboplastins.
PDP - products formed during the splitting (degradation) of fibrin under the action of plasmin.

Pathological anticoagulants

In some diseases, specific antibodies can form and accumulate in the blood that prevent blood clotting. They can be produced against any coagulation factors, but inhibitors of factors VIII and IX are most often formed. In some autoimmune diseases, abnormal proteins appear in the blood that have an antithrombin effect or suppress coagulation factors II, V, Xa.

Anticoagulants

Artificial anticoagulants, of which a large number have been developed, are indispensable drugs in modern medicine.

Indications for use

Indications for taking oral anticoagulants are:

myocardial infarctions;
pulmonary infarctions;
heart failure;
thrombophlebitis of the veins of the legs;
thrombosis of veins and arteries;
phlebeurysm;
thrombotic and embolic strokes;
embolic vascular lesions;
chronic aneurysm;
arrhythmias;
artificial heart valves;
prevention of atherosclerosis of the vessels of the brain, heart, peripheral arteries;
mitral heart defects;
thromboembolism after childbirth;
prevention of thrombus formation after surgical interventions.

Heparin is the main representative of the class of direct anticoagulants.

Classification of anticoagulants

Medicines in this group are divided into direct and indirect depending on the speed and mechanism of action, as well as the duration of the effect. Direct direct effects on blood coagulation factors and inhibit their activity. Indirect ones act indirectly: they slow down the synthesis of factors in the liver. Available in tablets, in solutions for injection, in the form of an ointment.

Direct

Drugs in this group act directly on clotting factors, so they are called fast-acting drugs. They prevent the formation of fibrin threads, prevent the formation of blood clots and stop the growth of existing ones. They are divided into several groups:

heparins;
hirudin;
low molecular weight heparin;
sodium hydrocitrate;
danaparoid, lepirudin.

Heparin ointment perfectly fights bruises, is used to treat thrombophlebitis and hemorrhoids

This is the most famous and common direct-acting anticoagulant. It is administered intravenously, under the skin and intramuscularly, and is also used as a local remedy in the form of an ointment. Heparin medications include:

Local heparins are characterized by low tissue permeability and not very high efficiency. Used to treat varicose veins, hemorrhoids, bruises. The most famous and often used are the following drugs with heparin:

Lyoton is a popular heparin-containing topical agent for varicose veins.

Heparins for intravenous and subcutaneous administration are a large group of medicines that are selected individually and are not replaced by one another during treatment, since they are not equivalent in effect. The activity of these drugs reaches its maximum after about three hours, and the action continues throughout the day. These heparins reduce the activity of tissue and plasma factors, block thrombin, prevent the formation of fibrin filaments, and prevent platelet aggregation.

For the treatment of deep vein thrombosis, heart attack, pulmonary embolism, angina pectoris, Nadroparin, Enoxaparin, Deltaparin are usually prescribed.

In order to prevent thromboembolism and thrombosis, Heparin and Reviparin are prescribed.

This anticoagulant is used in laboratory practice. To prevent blood from clotting, it is added to test tubes. It is used in the preservation of blood and components.

Indirect

They reduce the production in the liver of some coagulation factors (VIII, IX, X, prothrombin), slow down the formation of proteins S and C, and block the production of vitamin K.

These include:

Derivatives of indan -1,3-dione. Representative - Fenilin. This oral anticoagulant is available in tablets. Its action begins 8 hours after ingestion, reaches its maximum efficiency in a day. During the reception, it is necessary to control the prothrombin index and check the urine for the presence of blood in it.
Coumarin. In the natural environment, coumarin is found in plants (bison, sweet clover) in the form of sugars. For the first time, its derivative, dicoumarin, was used to treat thrombosis, which was isolated in the 20s of the 20th century from clover.

Indirect anticoagulants include the following drugs:

Warfarin should not be drunk with certain diseases of the kidneys and liver, thrombocytopenia, with acute bleeding and a tendency to bleeding, during pregnancy, with lactase deficiency, congenital deficiency of proteins C and S, DIC, if the absorption of galactose and glucose is impaired.

Warfarin is the main representative of the class of indirect anticoagulants.

Side effects include abdominal pain, vomiting, diarrhea, nausea, bleeding, urolithiasis, nephritis, alopecia, allergies. A rash on the skin, itching, eczema, vasculitis may appear.

The main disadvantage of Warfarin is a high risk of bleeding (gastrointestinal, nasal, and others).

New generation oral anticoagulants (NOACs)

Modern anticoagulants are indispensable means for the treatment of many diseases, such as heart attacks, thrombosis, arrhythmias, ischemia, and many others. Unfortunately, drugs that have proven to be effective have many side effects. But developments do not stop, and new oral anticoagulants periodically appear on the pharmaceutical market. PLAs have both advantages and disadvantages. Scientists are seeking to obtain universal remedies that can be taken for various diseases. Drugs are being developed for children, as well as for patients for whom they are currently contraindicated.

New anticoagulants have the following advantages:

when they are taken, the risk of bleeding is reduced;
the effect of the drug occurs within 2 hours and quickly stops;
drugs can be taken by patients for whom Warfarin was contraindicated;
the influence of other means and food consumed is reduced;
inhibition of thrombin and thrombin-related factor is reversible.

The new drugs also have disadvantages:

many tests for each remedy;
you need to drink regularly, while taking old medicines can be skipped due to the long action;
intolerance by some patients who did not have side effects when taking old pills;
risk of bleeding in the gastrointestinal tract.

As for indirect anticoagulants, they have not yet been developed that are radically different from Warfarin, Dicoumarin, Sincumar.

New drugs Apixaban, Rivaroxaban, Dabigatran can become an alternative for atrial fibrillation. Their main advantage is that they do not require constant blood donation during their use, and they do not interact with other drugs. At the same time, these drugs are just as effective and can prevent stroke in arrhythmias. As for the risk of bleeding, it is either the same or lower.

What you need to know

Patients who are prescribed oral anticoagulants should be aware that they have a large number of contraindications and side effects. When taking these drugs, you need to follow a diet and take additional blood tests. It is important to calculate the daily dose of vitamin K, since anticoagulants disrupt its metabolism; regularly monitor such a laboratory indicator as INR (or PTI). The patient should know the first symptoms of internal bleeding in order to seek help in time and change the drug.

Antiplatelet agents

Medicines in this group also help thin the blood and prevent blood clots, but they have a different mechanism of action. Disaggregants reduce blood clotting, due to the ability to inhibit platelet aggregation. They are prescribed to enhance the action of anticoagulants. In addition, they have an antispasmodic and vasodilating effect. The most popular antiplatelet agents:

Aspirin is the most famous of this group. It is considered a very effective remedy that dilates blood vessels, thins the blood and prevents the formation of blood clots.
Tirofiban - prevents platelets from sticking together.
Tiklopidin - is indicated for cardiac ischemia, heart attacks, for the prevention of thrombosis.
Dipyridamole is a vasodilator.
Eptifibatite - blocks the aggregation of platelets.

Aspirin is the most famous member of the antiplatelet group.

The new generation of drugs includes the drug Brilint with the active substance ticagrelor. It is a reversible P2U receptor antagonist.

Natural blood thinners

Adherents of treatment with folk methods are used to prevent thrombosis of grass with a blood-thinning effect. The list of such plants is quite long:

horse chestnut;
willow bark;
mulberry;
sweet clover;
wormwood;
meadowsweet:
Red clover;
liquorice root;
peony evasive;
chicory and others.

Before being treated with herbs, it is advisable to consult a doctor: not all plants can be useful.

Red clover is used in folk medicine as a means of improving blood flow.

Conclusion

Anticoagulants are indispensable drugs for the treatment of cardiovascular pathologies. You cannot take them on your own. They have many contraindications and side effects, and uncontrolled use of these drugs can lead to bleeding, including hidden ones. A doctor who is able to take into account all the features of the course of the disease and possible risks should prescribe them and determine the dosage. During treatment, regular laboratory monitoring is required.

It is important not to confuse anticoagulants and antiplatelet agents with thrombolytic agents. The main difference is that the former cannot destroy a blood clot, but only prevent or slow down its development. Thrombolytics are intravascular drugs that dissolve blood clots.

In one case, it was indicated that chicory, along with greens, should be removed from the diet, and chicory was named in the list of natural remedies (coagulants). So how do you know if it can be taken in parallel with warfarin or not?

List of drugs - anticoagulants of direct and indirect action, drugs that thin the blood

In a healthy human body, the coagulation and anticoagulation systems of the blood are in dynamic balance. At the same time, the blood flow through the vessels is not hindered, and there is no excessive thrombus formation, both with open bleeding and within the vascular bed.

If this balance is disturbed, conditions are created for thrombosis of small or large vessels or even the development of disseminated intravascular coagulation syndrome, in which multiple thrombi can lead to a rapid death.

However, a number of clinical situations lead to the fact that blood clots form out of place and out of time, clogging veins and arteries of various sizes.

Diseases in which clotting is increased

Acute venous thrombosis

Against the background of varicose veins of the lower extremities, phlebitis, as a postoperative complication
Thrombosis of the hemorrhoidal veins
Thrombosis in the system of the inferior vena cava

Acute arterial thrombosis

Pulmonary embolism (PE)
Ischemic stroke
myocardial infarction
Acute injuries of the arteries of the lower extremities against the background of atherosclerosis, inflammation, vessel injury

Syndrome of disseminated intravascular coagulation on the background of:

injury
sepsis due to the release of a large number of blood clotting factors from the tissues.

Treatment of all of these pathologies involves the use of anticoagulants, which are also called anticoagulants or blood thinners. These are drugs designed to reduce blood clotting and thereby restore its fluidity (rheological properties) and reduce the risk of recurrent thrombosis. Anticoagulants reduce the activity of tissue (fibrinogen, platelets) or plasma coagulation factors. The action of anticoagulants can be:

direct - direct anticoagulants
indirect - indirect anticoagulants

Prevention of heart diseases - in addition to the treatment of acute thrombosis, anticoagulant treatment is carried out for their prevention in unstable angina pectoris, various cardiac arrhythmias (permanent form of atrial fibrillation), with valvular heart disease, obliterating endarteritis, for patients on hemodialysis, after heart reconstruction operations (for example , coronary artery bypass grafting).

The third direction in the use of anticoagulants is the stabilization of blood components during its collection for laboratory research or their preparation for subsequent transfusion.

Direct acting anticoagulants

Heparins of local action

They are characterized by a small permeability in the tissue and a weaker effect. Used for local treatment of varicose veins, hemorrhoids, resorption of hematomas. List: Heparin ointment, Venolife, Lyoton gel, Venitan, Laventum, Trombless.

Heparin ointment

Lyoton gel

Trombless gel

Lavenum gel

Venolife

(Heparin + Dexpanthenol + Troxerutin) 40g. 400 rub.

Hepatrombin

Heparin + Allantoin + Dexpanthenol 40g. 300ME ointment 50 rubles, 500ME 40g. gel 300 rub.

Venitan Forte gal

(heparin + escin) price 50 gr. 250 rub.

Troxevasin NEO

(Heparin + Dexpanthenol + Troxerutin) 40 gr. 280 rub.

Heparins intravenous and subcutaneous administration

The second large group of direct anticoagulants are heparins, the mechanism of action of which is based on a combination of inhibition of plasma and tissue coagulation factors. On the one hand, these direct anticoagulants block thrombin and inhibit the formation of fibrin.

On the other hand, they reduce the activity of plasma coagulation factors (IXa, Xa, XIa, XIIa) and kallikrein. In the presence of antithrombin III, heparin binds to plasma proteins and neutralizes clotting factors. Heparins destroy fibrin and inhibit platelet aggregation.

The drugs are administered subcutaneously or intravenously (depending on the instructions). During treatment, one drug does not change to another (that is, the drugs are not equivalent and not interchangeable). The maximum activity of the drug develops after 2-4 hours, and the activity persists for a day.

Low molecular weight heparins

They have less effect on thrombin, predominantly inhibiting the clotting factor Xa. This improves tolerability and increases the effectiveness of low molecular weight heparins. Reduce platelet aggregation less than low molecular weight heparin anticoagulants. List of drugs:

Fraxiparine

(Nadroparin calcium) 1 syringe 380 rub.

Hemapaksan

(Enoxaparin sodium) 0.4 ml. 6 pcs. 1000 rub.

Clexane

(Enoxaparin sodium) 0.4 ml 1 sc. 350 rubles, Anfibra, Eniksum

(Deltaparin sodium) 2500ME 10 pcs. 1300 rub. 5000ME 10 pcs 1800 rub.

Klivarin

Troparin

Medium molecular weight heparins

These are the sodium and calcium salts of heparin. Heparin, Heparin Ferein 5 amp. rub.

How are heparins selected?

For the prevention of thrombosis and thromboembolism (including postoperative), Klivarin, Troparin are preferred.
For the treatment of thrombotic complications (unstable angina, heart attack, pulmonary embolism, deep vein thrombosis) - Fraxiparine, Fragmin, Clexane.
In the prevention of thrombosis in patients on hemodialysis: Fraxiparine, Fragmin.

Cybernin is an antithrombin III drug.

Similar to heparin in its action: blocks thrombin, coagulation factors IXa to XIIa, plasmin. During treatment, the level of antithrombin III in the blood plasma should be monitored.

Indications: The drug is used for thromboembolic complications against the background of congenital deficiency of antithrombin III or with its acquired shortage (against the background of liver cirrhosis with hepatic cell failure and severe jaundice, with DIC, in patients receiving hemodialysis, with thromboembolism of various origins). The drug is administered intravenously.

Contraindications: Cybernin is not used in cases of intolerance in children. Use with caution in pregnant women.

Side effects: Its use may be complicated by skin allergies (urticaria), dizziness, respiratory disorders, chills, fever, unpleasant taste in the mouth, blurred vision, cough, chest pains.

Direct acting antithrombotic agents

They work by directly blocking thrombin (plasma coagulation factor, which is formed from prothrombin activated by thromboplastin). Means of this group work similarly to hirudin, secreted by leeches and preventing blood clotting.

Recombinant natural hirudins (Desirudin, Lepirudin) block the active area of thrombin and fibrin.
Synthetic hirudin (Bivalrudin) is similar to them in the mechanism of action.
Melagatran and Efegatran carry out an isolated covalent blockade of the active part of thrombin.
Argatroban, Dabigatran, Ximelagatran, Inogatran, Etexipat is an isolated non-covalent blockade of thrombin.

Ximelagatran has shown great promise in the prevention of strokes. In experiments, he showed decent results and was not inferior in efficiency and bioavailability to Warfarin. However, further evidence has been accumulated that the drug causes serious liver damage, especially with prolonged use.

Fondaparinux (Arixtra) is a direct-acting parenteral anticoagulant that selectively inhibits coagulation factor Xa. It can be administered without APTT control subcutaneously in standard doses, taking into account the patient's body weight. The average dose is 2.5 mg per day.

The drug is excreted mainly by the kidneys, unchanged.

It is used for the prevention of thromboembolic complications in patients with major abdominal surgery, in long-term immobilized patients or in patients with joint arthroplasty. The drug is used to treat acute deep vein thrombosis of the lower extremities, PE, acute coronary syndrome.

The next direct anticoagulant is sodium hydrocytart

It is used exclusively for the conservation of blood and its components. It is he who is added to test tubes with blood in the laboratory so that it does not clot. By binding free calcium ions, sodium hydrocitrate prevents the formation of thromboplastin and the conversion of prothrombin to thrombin.

Indirect anticoagulants

Indirect anticoagulants are drugs that are opposite in action to vitamin K. They either reduce the formation of proteins (proteins C and S) involved in the anticoagulant system, or impede the formation of protorombin, VII, IX and X coagulation factors in the liver.

Indan-1-3dione derivatives are represented by Phenylin (Phenidion)

The drug is available in tablets of 0.03 grams (20 pcs. 160 rubles).
The drug works after 8-10 hours from the reception. The maximum effect occurs after hours. Less than warfarin accumulates in the body, does not give the effect of the total dose. Less effect on capillaries. Appointed under the control of PTI.
It is prescribed by a tablet in four doses on the first day, on the second by a tablet in three doses, then a tablet per day (depending on the level of PTI). In addition to monitoring PTI, urinalysis should be performed for the presence of red blood cells.
Poorly combined with hypoglycemic agents (Butamid).

Coumarin derivatives

In nature, coumarin in the form of sugars is found in many plants (aster, sweet clover, bison). In the isolated form, these are crystals that smell like fresh hay. Its derivative (dicumarin) was isolated in 1940 from rotting sweet clover and was first used to treat thrombosis.

This discovery was prompted by veterinarians who, in the 1920s, discovered that cows in the United States and Canada, grazing in meadows overgrown with sweet clover, began to die from massive bleeding. After that, dicoumarin was used for some time as a rat poison, and later began to be used as an anticoagulant drug. Subsequently, dicoumarin was replaced by neodicoumarin and warfarin from pharmaceuticals.

List of drugs: Warfarin (Warfarex, Marevan, Warfarin sodium), Neodicumarin (Ethylbiscumacetate), Acenocoumarol (Sinkumar).

It should be remembered that independent initiation of the use and selection of doses of Warfarin is strictly prohibited, due to the high risk of bleeding and stroke. Only a doctor who can correctly assess the clinical situation and risks can prescribe anticoagulants, as well as titrate doses.

The most popular indirect anticoagulant today is Vafarin.

The action of the drug and indications for use

Warfarin is available under various commercial names in tablets of 2.5, 3, and 5 mg. If you start taking pills, they will begin to act after an hour, and the maximum therapeutic effect will appear by 5-7 days from the start of treatment. If the drug is canceled, then the normal functioning of the blood coagulation system will return after 5 days. Indications for the appointment of warfarin are most often all typical cases of thrombosis and thromboembolism.

Dosages

The drug is taken once a day at the same time. Start with 2 tablets per day (daily dose of 5 mg). Dose adjustment is carried out for 2-5 days after the control of clotting parameters (INR). Maintenance dosages remain within 1-3 tablets (2.5-7.5 mg) per day. The duration of taking the drug depends on the type of pathology. So, with atrial fibrillation, cardiac defects, the drug is recommended for continuous use, PE requires treatment for about six months (if it occurred spontaneously or its cause was eliminated surgically) or is carried out for life (if it occurred against the background of thrombophlebitis of the veins of the legs).

Side effects

Among the side effects of warfarin are bleeding, nausea and vomiting, diarrhea, abdominal pain, skin reactions (urticaria, skin itching, eczema, necrosis, vasculitis, nephritis, urolithiasis, hair loss).

Contraindications

Warfarin should not be used for acute bleeding, DIC, severe liver or kidney disease with creatinine greater than 140 µmol per liter, thrombocytopenia, in persons with a predisposition to bleeding (peptic ulcer, severe wounds, bacterial endocarditis, esophageal varicose veins, hemorrhoids, arterial aneurysms), in the first 12 and last 4 weeks of pregnancy. Also, the drug is not recommended for malabsorption of glucose and galactose, with lactase deficiency. Warfarin is also not indicated for congenital deficiency of S and C proteins in blood plasma.

Simultaneous eating:

There is a whole list of foods that need to be eaten with caution or completely avoided during treatment with warfarin, as they increase bleeding and increase the risk of bleeding. These are garlic, sage and quinine contained in tonics, papaya, avocado, onion, cabbage, broccoli and Brussels sprouts, cucumber peel, lettuce and watercress, kiwi, mint, spinach, parsley, peas, soybeans, watercress, turnips , olive oil, peas, cilantro, pistachios, chicory. Alcohol also increases the risk of bleeding.

St. John's wort, on the contrary, reduces the effectiveness of the drug and should not be used simultaneously with it.

Medications that are contraindicated at the same time as warfarin

NSAIDs (except COX-2 inhibitors), Clopidogrel, Aspirin, Dipyridamole, high dose penicillins, Cimetidine, Chloramphenicol.

Drugs that increase the effect of warfarin

Allopurinol, Digoxin, Amiodarone, Quinidine, Disopyramide, Disulfiram, Amitriptyline, Sertraline, Heparin, Bezafibrate, Clofibrate, Fenofibrate, Vitamins A and E, Glucagon, Glibenclamide, Gingo Bilboa, Influenza Vaccine, Ifosfamide, Methotrexate, Etoposide, Tegafur, Zafirlukast , Cimetidine, Indomethacin, Codeine, Metolazone, Piroxicam. Parksetin, Proguanil, Omeprazole, Simvastatin, Propafenone, Sulindac, Sulfapyrazone, Testosterone, Danazol, Tamoxifen, Fluoxetine, Troglitazone, Phenylbutazone, Flucanazole, Itraconazole, Levamisole, Miconazole, Lovastatin, Celecoxib, Cefalexin, Ciprofloxacin, Norfloxacin, Ofloxacin, Erythromycin, Azithromycin, Tetracyclines, Cefuroxime, Clarithromycin, Chloramphenicol, Sulfamethoxazole.

What is INR and why determine it

INR (International Normalized Ratio) is an indicator of blood clotting, which is examined before prescribing warfarin and as a control of the effectiveness of therapy, as well as for dose adjustment and risk assessment of treatment complications. This is a derivative of prothrombin time (during which blood coagulates), as well as PTI (prothrombin index), which is normally %.

INR is the ratio of the patient's prothrombin time to the standard prothrombin time. The more INR, the worse blood clotting.
The INR norm is 0.85-1.25. During therapy with warfarin, you need to achieve an INR of 2-3

INR is checked before starting warfarin, then on days 2-5. On average, it takes up to 10 days to select the dose of the drug and stabilize the INR within the target numbers (2-3). In the future, control is carried out once every 2-4 weeks.

If the INR is less than 2 - the dose of warfarin is insufficient, it is increased by 2.5 mg (1 tablet per week) by monitoring the INR every week until indicators of 2-3 are reached.
If the INR is more than 3, then the dose of the drug is reduced (1 tablet 2.5 mg per week). INR control is carried out one week after dose reduction.
If the INR is 3.51-4.5, reduce the dose by 1 tablet. INR is monitored after 3 days.
If the INR is 4.51-6, reduce the dose by 1 tablet with INR control every other day.
If the INR is greater than 6, warfarin is canceled.

In general, anticoagulants are drugs with many pitfalls. The main of which are the risks of spontaneous bleeding (including latent) and brain catastrophes that can lead to death. In this regard, anticoagulant drugs should be taken only as prescribed and under the supervision of a physician, taking into account all the circumstances of the disease, the risks in this patient and the data of laboratory monitoring, which should be thorough and regular.

New in the use of anticoagulants

Titration (gradual selection of doses) of Warfarin for maintenance therapy goes through two stages: the actual selection of the dose and long-term treatment with maintenance doses. Today, all patients, depending on the sensitivity to the drug, are divided into three groups.

highly sensitive to warfarin. They quickly (in a few days) from the start of taking the drug achieve therapeutic target values of INR. Further attempts to increase the dose lead to high risks of bleeding.
Individuals with normal sensitivity achieve target INR numbers on average after a week from the start of therapy.
Patients with reduced sensitivity to Warfarin, even at high doses for two to three weeks, do not give an adequate INR response.

These features of the bioavailability of Warfarin in different patients may require more careful (frequent) laboratory monitoring of INR during the treatment period, tying patients to laboratories. The patient can save relative freedom of movement and life by purchasing a simple Koaguchek device, which works similarly to a glucometer using test strips. True, the price tag for the device itself is about rubles, and consumables (a set of test strips) will cost six to seven thousand.

Today, a new generation of anticoagulants, which successfully replace Warfarin in many situations (cardiology, prevention and treatment of deep vein thrombosis of the extremities, pulmonary embolism, in the treatment and prevention of strokes), makes it possible to get away from the problem of INR control.

We are talking about three main drugs: Rivaroxaban (Xarelto), Apixaban (Eliquis) and Dabigatran (Pradaxa).

The first two have successfully replaced parenteral anticoagulants in combination with warfarin in low-risk PE situations today.

Rivaroxaban (tablets 10, 15, 20 mg)

It shows the lowest risk of bleeding, is safer for this group of complications in comparison with the combination of Warfarin with Enoxaparin. The effect of therapy is quickly manifested, control of INR is not required. In the treatment of PE or in deep vein thrombosis of the lower extremities, 15 mg of the drug is prescribed twice a day for 3 weeks. Then they switch to a maintenance dosage of 20 mg once a day for months.

Apixaban

In the same situation, Apixaban is given at doses of 10 mg twice daily for a week, followed by 5 mg twice daily for life. The drugs are promising in terms of outpatient therapy for low-risk pulmonary embolisms, which are currently treated inpatients.

These drugs are contraindicated in:

ongoing bleeding
in pregnant women
terminal stages of renal failure,
severe hepatic pathologies.

Dabigatran

It cannot replace parenteral anticoagulants and is prescribed after treatment with them at a dose of 150 mg twice a day (110 mg twice in people over 80 years of age or receiving verapamil). In the treatment of ischemic strokes, Apixaban is the safest, which is prescribed for a small stroke on days 3-5, with an average of 6 days (after a CT scan of the brain), with a severe one after 12 days.

It is interesting to use these drugs in the prevention of pulmonary embolism in patients with hip and knee arthroplasty. On average, anticoagulant therapy should begin 1-4 hours after surgery.

In the case of Rivaroxaban, it is used for 35 days for hip surgery and 14 days for knee replacement.
Dabigatran 35 and 10 days, respectively.

In cardiological practice, against the background of atrial fibrillation, stroke prevention can be carried out instead of Warfarin by any of these drugs. At the same time, Dabigatran (110 mg twice a day) and Apixaban (5 mg 2 times a day) are more effective than Warfarin and have a lower risk of bleeding. Both Dabigatran, Apixaban, and Rivaroxaban compared with Warfarin in these situations give lower statistics of complications such as hemorrhagic stroke. Rivaroxaban for the prevention of ischemic stroke secondary to atrial fibrillation at doses of 20 mg once daily has no advantage over warfarin.

In the presence of mechanical prostheses of the heart valves, as well as in mitral stenosis, the transition from warfarin to new anticoagulants is impractical.

How to switch from one anticoagulant to another

The term new anticoagulants includes Rivoraxoban, Apixaban, Dabigatran.

If it is necessary to switch from Warfarin to one of the new anticoagulants, Warfarin is canceled and the period is maintained until the INR is less than 2. When this value is reached, one of the new anticoagulants is prescribed.
If you need to replace a new anticoagulant with Warfarin, then it is simply added to the new anticoagulant until an INR of 2-3 is obtained. INR should be monitored before the next dose of a new anticoagulant with repeated control one day after the last dose of a new anticoagulant.
If the transition is made from parenteral forms of anticoagulants to new ones, then the first ones are immediately canceled, and a new one is given the next day.

How to compensate for wrong reception

Often, patients (especially the elderly) make mistakes in the dosage regimen of the drug or simply forget if they took it at all. In order not to get into extreme situations of bleeding or a sharp increase in the risk of thrombosis, there are certain rules for correcting errors in taking new generation anticoagulants.

If a tablet is missed, then a double dose should not be taken in any case. If the drug is usually taken twice a day (Pradaxa, Eliquis), the missed tablet can be taken within 6 hours after the missed time. For Xarelto, the same can be done within 12 hours. If such a dose is not possible, the dose should be skipped, and the next one should be taken as planned.
If the patient accidentally took a double dose of the drug with a twice daily intake (Pradaxa, Eliquis), then the next medication should be skipped according to the plan. If a double dose was eaten for Xarelto, there is no need to skip, take the drug as usual.
If the patient does not remember whether he took the pill, then Pradaxa and Eliquis do not require an additional dose, the next dose of the drug should be only 12 hours after the previous one. For Xarelto, a tablet should be taken, the next one should be taken after 24 hours.

Bleeding problem

As with warfarin, bleeding of varying severity can develop with the new anticoagulants. With light bleeding, the anticoagulant will have to be discontinued. In moderate cases, erythromas, thromboconcentrate or freshly frozen plasma are additionally dripped. Life-threatening bleeding requires prothrombin complex concentrate or surgical treatment.

There are no specific antidotes for warfarin (neither Vikasol nor Etamzilat are suitable).

To date, the antidote Idarucizumab has been registered and used for Dabigatran in Europe. In the Russian Federation, its registration is planned for 2017. Most often, the drug is used in emergency situations (for example, with life-threatening bleeding or emergency surgical intervention).

Preoperative preparation

All major surgical interventions require switching the patient from warfarin or new anticoagulants to parenteral low molecular weight heparins.

However, minor surgery can be provided to the patient without changing anticoagulation therapy. In particular, patients can be managed on Warfarin or new anticoagulants:

dentists (when removing 1-3 teeth, installing an implant, periodontal surgery, opening abscesses of the oral cavity),
ophthalmologists (removal of cataracts, when operating on glaucoma).
Does not require changing the anticoagulant and diagnostic endoscopy.

The only detailed and specific article of all publications on anticoagulants, sincere thanks to all who worked on this material. Health to you!

Thank you, the material was very helpful.

Thank you for the detailed explanation. Useful information I am not taking anticoagulants yet, but already prescribed Price unaffordable for pensioners, this is a problem

And if I take Cardiomagnyl, can I take Xarelto? And what is the difference between them?

Add a comment Cancel reply

Do you know about colds and flu?