Indications for the use of anticoagulants. Indirect anticoagulants: indications and contraindications

To avoid the occurrence of blood clots, as dangerous blood clots, in the classification of drugs there is a pharmacological group called anticoagulants - a list of drugs is presented in any medical reference book. Such medications provide control of blood viscosity, prevent a number of pathological processes, and successfully treat certain diseases of the hematopoietic system. For the recovery to be complete, the first step is to identify and remove the clotting factors.

What are anticoagulants

These are representatives of a separate pharmacological group, produced in the form of tablets and injections, which are intended to reduce blood viscosity, prevent thrombosis, prevent stroke, and in the complex therapy of myocardial infarction. Such medications not only productively reduce the coagulation of the systemic bloodstream, but also maintain the elasticity of the vascular walls. With increased platelet activity, anticoagulants block the formation of fibrin, which is relevant for the successful treatment of thrombosis.

Indications for use

Anticoagulants are used not only for the successful prevention of thromboembolism; such a prescription is suitable for increased thrombin activity and the potential threat of the formation of blood clots in the vascular walls that are dangerous to the systemic blood flow. The platelet concentration gradually decreases, the blood acquires an acceptable flow rate, and the disease recedes. The list of drugs approved for use is extensive, and they are prescribed by specialists for:

atherosclerosis;
liver diseases;
vein thrombosis;
vascular diseases;
thrombosis of the inferior vena cava;
thromboembolism;
blood clots of hemorrhoidal veins;
phlebitis;
injuries of various etiologies;
varicose veins

Classification

The benefits of natural anticoagulants, which are synthesized by the body and prevail in sufficient concentration to control blood viscosity, are obvious. However, natural coagulation inhibitors can be susceptible to a number of pathological processes, so there is a need to introduce synthetic anticoagulants into the complex treatment regimen. Before determining the list of medications, the patient needs to consult a doctor to rule out potential health complications.

Direct anticoagulants

The list of such drugs is designed to suppress thrombin activity, reduce fibrin synthesis, and normal liver function. These are local heparins for subcutaneous or intravenous administration, necessary for the treatment of varicose veins of the lower extremities. The active components are productively absorbed into the systemic bloodstream, act throughout the day, and are more effective when administered subcutaneously than when administered orally. Among low-molecular-weight heparins, doctors identify the following list of drugs intended for administering heparins topically, intravenously or orally:

Fraxiparine;
Lyoton-gel;
Clexane;
Fragmin;
Hepatrombin;
Sodium hydrogen citrate (heparin is administered intravenously);
Klivarin.

Indirect anticoagulants

These are long-acting drugs that act directly on blood clotting. Indirect anticoagulants promote the formation of prothrombin in the liver and contain vitamins valuable for the body in their chemical composition. For example, Warfarin is prescribed for atrial fibrillation and artificial heart valves, while the recommended doses of Aspirin are less effective in practice. The list of drugs is represented by the following classification of the coumarin series:

monocoumarins: Warfarin, Sinkumar, Mrakumar;
indandiones: Phenilin, Omefin, Dipaxin;
Dicoumarins: Dicoumarin, Tromexane.

To quickly normalize blood clotting and prevent vascular thrombosis after a myocardial infarction or stroke, doctors strongly recommend oral anticoagulants containing vitamin K in their chemical composition. These types of medications are also prescribed for other pathologies of the cardiovascular system that are prone to chronicity and relapses. In the absence of extensive kidney disease, the following list of oral anticoagulants should be highlighted:

Sinkumar;
Warfarex;
Acenocoumarol;
Neodicoumarin;
Fenilin.

NOAC anticoagulants

This is a new generation of oral and parenteral anticoagulants, which are being developed by modern scientists. Among the advantages of this prescription are a quick effect, complete safety with respect to the risk of bleeding, and reversible inhibition of thrombin. However, there are also disadvantages of such oral anticoagulants, and here is a list of them: bleeding into the gastrointestinal tract, the presence of side effects and contraindications. In addition, to ensure a long-term therapeutic effect, thrombin inhibitors must be taken for a long time, without violating the recommended daily doses.

The drugs are universal, but the effect in the affected body is more selective, is temporary, and requires long-term use. In order to normalize blood clotting without serious complications, it is recommended to take one of the stated list of new generation oral anticoagulants:

Apixaban;
Rivaroxaban;
Dabigatran.

Price for anticoagulants

If it is necessary to reduce blood clotting as soon as possible, doctors strictly for medical reasons recommend taking anticoagulants - the list of drugs is extensive. The final choice depends on the pharmacological characteristics of a particular medicine, the cost in pharmacies. Prices vary, but you need to pay more attention to the therapeutic effect. Below you can learn more about the prices in Moscow, but do not forget the main criteria for such a purchase. So:

Video

Anticoagulants are anticoagulants that prevent blood clots from forming in the bloodstream. They maintain blood in a liquid state and ensure its fluidity with the integrity of blood vessels. They are divided into natural anticoagulants and synthetic ones. 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 ones appear in the blood in some diseases.

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

Primary natural anticoagulants

They are usually divided into groups:

Antithromboplastins.
Antithrombins.
Inhibitors of fibrin self-assembly.

When the level of primary physiological anticoagulants in the blood decreases, 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 quantities in the lungs and liver. In large doses, it interferes with the blood clotting process at all stages and suppresses a number of platelet functions.
Antithrombin III. Synthesized in the liver, it belongs to alpha₂-glycoproteins. Reduces the activity of thrombin and some activated coagulation factors, but does not affect non-activated factors. The anticoagulant activity of plasma is 75% provided by antithrombin III.
Protein C. It is synthesized by liver parenchyma cells and is in an inactive form in the blood. 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 inhibitor-I.

Secondary physiological anticoagulants

As already mentioned, they are formed during the process of blood coagulation and the dissolution of fibrin clots during the breakdown of certain coagulation factors, which, due to degradation, lose their coagulation properties and acquire anticoagulation properties. These include:

Antithrombin I.
Antithrombin IX.
Metafactors XIa and Va.
Febrinopeptides.
Auto-II anticoagulant.
Antithromboplastins.
PDF are products formed during the breakdown (degradation) of fibrin under the influence of plasmin.

Pathological anticoagulants

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

Anticoagulant drugs

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 infarction;
pulmonary infarctions;
heart failure;
thrombophlebitis of the leg veins;
thrombosis of veins and arteries;
phlebeurysm;
thrombotic and embolic strokes;
embolic vascular lesions;
chronic aneurysm;
arrhythmias;
artificial heart valves;
prevention of atherosclerosis of blood vessels in the brain, heart, and peripheral arteries;
mitral heart defects;
thromboembolism after childbirth;
prevention of thrombosis after surgery.

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 directly affect blood clotting factors and inhibit their activity. Indirect ones act indirectly: they slow down the synthesis of factors in the liver. Available in tablets, injection solutions, and ointment form.

Direct

Medicines in this group act directly on coagulation factors, which is why 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 hydrogen citrate;
danaparoid, lepirudin.

Heparin ointment is excellent against bruises and is used to treat thrombophlebitis and hemorrhoids

This is the most famous and widespread direct-acting anticoagulant. It is administered intravenously, subcutaneously and intramuscularly, and is also used as a topical ointment. Heparin-type drugs include:

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

Topical heparins have low tissue permeability and are not very effective. Used to treat varicose veins of the legs, hemorrhoids, and bruises. The most well-known and often used are the following heparin products:

Lyoton gel;
Trombless gel;
Venolife;
Hepatrombin;
Troxevasin NEO.

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

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

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

To prevent thromboembolism and thrombosis, Heparin and Reviparin are prescribed.

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

Indirect

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

These include:

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

Indirect anticoagulants include the following drugs:

Acenocoumarol,
Neodicoumarin.

It is worth dwelling in more detail on Warfarin, the most popular drug. Available in tablets. Its effect occurs after 1.5 - 2 days, maximum effectiveness - after about a week. Warfarin is prescribed for heart defects, atrial fibrillation, and pulmonary embolism. Treatment is often lifelong.

Warfarin should not be taken in case of certain kidney and liver diseases, thrombocytopenia, acute bleeding and tendency to bleed, during pregnancy, lactase deficiency, congenital deficiency of proteins C and S, disseminated intravascular coagulation syndrome, 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 skin rash, itching, eczema, and vasculitis may appear.

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

New generation oral anticoagulants (NOACs)

Modern anticoagulants are an 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 trying 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 taking them, the risk of bleeding is reduced;
the effect of the medicine occurs within 2 hours and quickly ceases;
the drugs can be taken by patients for whom Warfarin is contraindicated;
the influence of other drugs and food consumed is reduced;
inhibition of thrombin and thrombin-binding factor is reversible.

The new drugs also have disadvantages:

many tests for each product;
it is necessary to drink regularly, while old medications can be skipped due to their long-term effects;
intolerance by some patients who had no side effects when taking the old pills;
risk of bleeding in the gastrointestinal tract.

The list of new drugs is still small. One of the direct NOACs is Dabigatran. It is a low molecular weight anticoagulant and thrombin inhibitor. Most often it is prescribed as a prophylactic agent for venous thromboembolism.

As for indirect anticoagulants, they have not yet been developed that are radically different from Warfarin, Dicumarin, and Sinkumar.

New drugs Apixaban, Rivaroxaban, Dabigatran may become an alternative for atrial fibrillation. Their main advantage is that they do not require constant blood donation while taking them, and they do not interact with other medications. At the same time, these drugs are just as effective and can prevent stroke due to arrhythmia. As for the risk of bleeding, it is either the same or lower.

What you need to know

Patients prescribed oral anticoagulants should be aware that they have a large number of contraindications and side effects. When taking these medications, you need to follow a diet and take additional blood tests. It is important to calculate your daily dose of vitamin K, since anticoagulants interfere with its metabolism; Regularly monitor laboratory indicators such as INR (or INR). 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 promote and prevent the formation of blood clots, but their mechanism of action is different. Antiplatelet agents reduce blood clotting due to their ability to inhibit platelet aggregation. They are prescribed to enhance the effect 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 platelet aggregation.
Ticlopidine - indicated for cardiac ischemia, heart attacks, for.
Dipyridamole is a vasodilator.
Eptifibatitis – blocks platelet aggregation.

Aspirin is the most famous representative of the group of antiplatelet drugs

A new generation of drugs includes the drug Brilint with the active substance ticagrelor. It is a reversible antagonist of the P2Y receptor.

Natural blood thinners

Adherents of traditional treatment methods use herbs with a blood-thinning effect to prevent thrombosis. The list of such plants is quite long:

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

Before using herbs, it is advisable to consult a doctor: not all plants can be beneficial.

Red clover is used in folk medicine as a means to improve 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 medications can lead to bleeding, including hidden bleeding. They should be prescribed and the dosage determined by a doctor who is able to take into account all the features of the course of the disease and possible risks. 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 a healthy human body, the blood coagulation and anticoagulation systems are in dynamic equilibrium. At the same time, the flow of blood through the vessels is not hampered, and there is no excessive thrombus formation, both during open bleeding and inside the vascular bed.

When 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 blood clots can lead to rapid death.

However, a number of clinical situations lead to blood clots forming in the wrong place and at the wrong time, clogging veins and arteries of different sizes.

Diseases in which coagulability is increased

Acute venous thrombosis

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

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, vascular injury

Disseminated intravascular coagulation syndrome due to:

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

Treatment of all listed pathologies involves the use of anticoagulants, which are also called. These are medications 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 effect of anticoagulants can be:

direct - direct anticoagulants
indirect - indirect anticoagulants

Prevention of heart disease- in addition to the treatment of acute thrombosis, treatment with anticoagulants is carried out for their prevention in cases of unstable angina, various heart rhythm disturbances (a permanent form of atrial fibrillation), for heart valve defects, obliterating endarteritis, for patients on hemodialysis, after reconstructive operations not on the heart (for example, coronary artery bypass surgery ).

The third direction of use of anticoagulants– this is the stabilization of blood components when it is collected for laboratory tests or prepared for subsequent transfusion.

Direct anticoagulants

Topical heparins

They are characterized by low tissue permeability 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 30 gr. 400 rub.	Trombless gel 30 gr. 250 rub.	Lavenum gel 30 gr. 180 rub.

Venolife (Heparin + Dexpanthenol + Troxerutin) 40g. 400 rub.	Hepatrombin Heparin+ Allantoin+ Dexpanthenol 40g. 300IU ointment 50 rubles, 500IU 40g. gel 300 rub.	Venitan Forte gal (heparin+escin) price 50 g. 250 rub.	Troxevasin NEO (Heparin + Dexpanthenol + Troxerutin) 40 gr. 280 rub.

Heparins for 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 fibrin formation.

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 coagulation factors. Heparins destroy fibrin and inhibit platelet adhesion.

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 are not interchangeable). The maximum activity of the drug develops after 2-4 hours, and activity persists throughout the day.

Low molecular weight heparins

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

Fraxiparine

(Nadroparin calcium) 1 syringe 380 rub.

Hemapaxan

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

Clexane

(Enoxaparin sodium) 0.4 ml 1 spr. 350 rub., Anfiber, Enixum

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

Klivarin

(Reviparin sodium)

Troparin

(Heparin sodium)

These are the sodium and calcium salts of heparin. Heparin, Heparin Ferein 5 amp. 500-600 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.
For the prevention of thrombus formation in patients on hemodialysis: Fraxiparine, Fragmin.

Cybernine – antithrombin III drug

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

Indications: The drug is used for thromboembolic complications due to congenital deficiency of antithrombin III or its acquired deficiency (against the background of hepatic cell failure and severe jaundice, with disseminated intravascular coagulation syndrome, in patients receiving hemodialysis, with thromboembolism of various origins). The drug is prescribed intravenously.
Contraindications: Cybernine 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, breathing problems, chills, fever, unpleasant taste in the mouth, blurred vision, cough, chest pain.

Direct acting antithrombotics

They work by directly blocking thrombin (a plasma clotting factor that is formed from prothrombin activated by thromboplastin). The drugs in this group work similarly to hirudin, secreted by leeches and preventing blood clotting.

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

Ximelagatran has been associated with great promise in the prevention of strokes. In experiments, it showed decent results and was not inferior in effectiveness and bioavailability to Warfarin. However, further evidence has accumulated that the drug causes serious liver damage, especially with long-term use.

Fondaparinux (Arixtra)
is a direct-acting parenteral anticoagulant that selectively inhibits coagulation factor Xa. It can be administered subcutaneously without APTT monitoring 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.

Used for the prevention of thromboembolic complications in patients undergoing major abdominal surgery, in long-term immobilized patients or patients undergoing joint replacement. The drug treats acute deep vein thrombosis of the lower extremities, pulmonary embolism, and acute coronary syndrome.

The next direct anticoagulant is sodium hydrocytart.

It is used exclusively for the preservation of blood and its components. This is what is added to test tubes with blood in the laboratory to prevent it from clotting. By binding free calcium ions, sodium hydrogen citrate prevents the formation of thromboplastin and the conversion of prothrombin to thrombin.

Indirect anticoagulants

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

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

The drug is available in tablets of 0.03 grams (20 pieces, 160 rubles).
The drug works within 8-10 hours of administration. The maximum effect occurs after 24-30 hours. It accumulates in the body less than warfarin and does not produce the effect of the total dose. Less effect on capillaries. Prescribed under the supervision of PTI.
It is prescribed one tablet in four doses on the first day, on the second day one tablet in three doses, then one tablet per day (depending on the level of IPT). In addition to monitoring IPT, urine tests should be performed to check for the appearance of red blood cells.
Does not combine well with hypoglycemic agents (Butamide).

Coumarin derivatives

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

This discovery of pharmacists was prompted by veterinarians who, in the 20s of the last century, discovered that cows in the USA and Canada, grazing in meadows overgrown with clover, began to die from massive bleeding. After this, dicoumarin was used for some time as a rat poison, and later began to be used as an anti-clotting drug. Subsequently, dicoumarin was replaced from pharmaceuticals by neodicoumarin and warfarin.

List of drugs: Warfarin (Warfarex, Marevan, Warfarin sodium), Neodicoumarin (Ethylbiscoumacetate), Acenocoumarol (Sincumar).

It should be remembered that independent initiation of use and selection of doses of Warfarin are strictly prohibited, due to the high risks of bleeding and strokes. Only a doctor who can competently assess the clinical situation and risks can prescribe anticoagulants and titrate doses.

The most popular indirect anticoagulant today is Wafarin.

Effect of the drug and indications for use

Warfarin is available under different commercial names in tablets of 2.5, 3 and 5 mg. If you start taking the tablets, they will begin to act after 36-72 hours, and the maximum therapeutic effect will appear by 5-7 days from the start of treatment. If the drug is discontinued, normal functioning of the blood coagulation system will return after 5 days. Indications for prescribing 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 5 mg). Dose adjustment is carried out on days 2-5 after monitoring coagulation 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. Thus, for atrial fibrillation and 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

Side effects of warfarin include bleeding, nausea and vomiting, diarrhea, abdominal pain, skin reactions (urticaria, eczema, necrosis, nephritis, urolithiasis, hair loss).

Contraindications

Warfarin should absolutely not be used in acute bleeding, disseminated intravascular coagulation syndrome, severe liver or kidney diseases with creatinine more than 140 µmol per liter, thrombocytopenia, in persons with a predisposition to bleeding (peptic ulcer, severe wounds, bacterial endocarditis, esophageal varices, hemorrhoids, arterial aneurysms), in the first 12 and last 4 weeks of pregnancy. Also, the drug is not recommended for impaired absorption of glucose and galactose, or for lactase deficiency. Warfarin is also not indicated for congenital deficiency of proteins S and C in the blood plasma.

Simultaneous food intake:

There is a whole list of foods that should be consumed with caution or completely excluded during warfarin treatment, as they increase bleeding and increase the risk of bleeding. This is garlic, and quinine contained in tonics, papaya, avocado, onions, cabbage, broccoli and Brussels sprouts, cucumber peel, lettuce and watercress, kiwi, mint, spinach, parsley, peas, soybeans, watercress, turnips, olive oil, peas, cilantro, pistachios, . Alcohol also increases the risk of bleeding.

On the contrary, it reduces the effectiveness of the drug and should not be used simultaneously with it.

Medicines that are contraindicated with warfarin

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

Medicines 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, Flu vaccine, Ifosfamide, Methotrexate, Etoposide, Tegafur, For firlukast, Cimetidine, Indomethacin, Codeine, Metolazone, Piroxicam. Parksetin, Proguanil, Simvastatin, Propafenone, Sulindac, Sulfapyrazone, Testosterone, Danazol, Tamoxifen, Fluoxetine, Troglitazone, Phenylbutazone, Flucanazole, Itraconazole, Levamisole, Miconazole, Lovastatin, Celecoxib, Cephalexin, Ciprofloxacin, Norfloxacin, Ofloxacin, Erythromycin, A zithromycin, tetracyclines, Cefuroxime, Clarithromycin, Chloramphenicol, Sulfamethoxazole.

What is INR and why should it be determined?

INR (International Normalized Ratio) is an indicator of blood clotting that is studied before prescribing warfarin and as a control for the effectiveness of therapy, as well as for adjusting dosages and assessing the risks of treatment complications. This is a derivative of prothrombin time (during which the blood clots), like PTI (prothrombin index), which is normally 95-105%.

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

The 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, monitoring 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), monitoring the INR every week until it reaches 2-3.
If the INR is more than 3, then the dose of the drug is reduced (1 tablet 2.5 mg per week). INR monitoring 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 monitoring every other day.
If the INR is greater than 6, warfarin is discontinued.

In general, anticoagulants are drugs with many pitfalls. The main ones are the risks of spontaneous bleeding (including hidden) and brain accidents 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 of the patient and laboratory monitoring data, which should be thorough and regular.

New in the use of anticoagulants

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

Highly sensitive to Warfarin. They quickly (within a few days) from the start of taking the drug achieve therapeutic target INR values. Further attempts to increase the dose lead to a high risk of bleeding.
Individuals with normal sensitivity achieve target INR values 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, linking patients to laboratories. The patient can maintain relative freedom of movement and life by purchasing a simple Coaguchek device, which works similarly to a glucometer using test strips. True, the price tag for the device itself is about 30,000 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), allows us 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 are now successfully replacing parenteral anticoagulants in combination with warfarin in low-risk situations of pulmonary embolism.

Rivaroxaban (tablets 10, 15, 20 mg)

It shows the lowest risk of bleeding and is safer in this group of complications compared to the combination of Warfarin and Enoxaparin. The effect of therapy appears quickly; INR monitoring is not required. In the treatment of pulmonary embolism or 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 3-6-12 months.

Apixaban

In the same situation, Apixaban is given in doses of 10 mg twice a day for a week, followed by 5 mg twice a day for life. The drugs are promising in terms of outpatient treatment of low-risk pulmonary embolism, which is currently treated in an inpatient setting.

These drugs are contraindicated if:

ongoing bleeding
in pregnant women,
end stages of renal failure,
severe liver 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 minor strokes on days 3-5, on average on days 6 (after a brain CT scan), and for severe strokes after 12 days.

The use of these drugs in the prevention of pulmonary embolism in patients with hip and knee replacement is also interesting. 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 their use has 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 due to atrial fibrillation in doses of 20 mg once a day has no advantages over Warfarin.

In the presence of mechanical prosthetic heart valves, as well as with mitral stenosis, switching 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 discontinued and a 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. The INR should be monitored before the next dose of a new anticoagulant, with repeated monitoring one day after the last dose of the new anticoagulant.
If a 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 incorrect reception

Often patients (especially older ones) make mistakes in the dosage regimen of the drug or simply forget whether they took it at all. In order to avoid 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 you miss taking a pill, then under no circumstances should you take a double dose. 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 this is not possible, the dose should be skipped and the next one taken as planned.
If the patient accidentally took a double dose of a twice-daily drug (Pradaxa, Eliquis), then the next scheduled dose of the drug should be skipped. If a double dose was taken for Xarelto, there is no need to skip it, take the drug as usual.
If the patient does not remember whether he took the tablet, then for Pradaxa and Eliquis an additional dose is not required; the next dose of the drug should be only 12 hours after the previous one. For Xarelto, you should take one tablet and consume the next one after 24 hours.

Bleeding problem

As with Warfarin, bleeding of varying severity may develop with new anticoagulants. If bleeding is light, the anticoagulant will have to be discontinued. For moderate cases, additional drops of erythromass, platelet concentrate or fresh frozen plasma are added. Life-threatening bleeding requires prothrombin complex concentrate or surgical treatment.

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

Today, the antidote Idarucizumab is registered and used in Europe for Dabigatran. Its registration in the Russian Federation is planned for 2017. Most often, the drug is used in emergency situations (for example, in case of life-threatening bleeding or emergency surgical care).

Preoperative preparation

All major surgical interventions require transferring 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 may be treated on Warfarin or new anticoagulants:

dentists (for removal of 1-3 teeth, installation of an implant, periodontal surgery, opening of oral abscesses),
ophthalmologists (cataract removal, glaucoma surgery).
Diagnostic endoscopy does not require changing the anticoagulant.

Anticoagulants are a group of drugs that inhibit blood clotting and prevent blood clots 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: as ointments, tablets or injection solutions.

Only a specialist can choose the right medications and select their dosage.

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

The high mortality rate due to cardiovascular diseases is explained by the formation of blood clots: thrombosis was detected in almost half of those who died from cardiac pathology.

Venous thrombosis and pulmonary embolism are the most common causes of disability and mortality. Therefore, cardiologists recommend starting to use anticoagulants immediately after detection of vascular and heart diseases.

Their early use helps prevent the formation and enlargement of a blood clot and 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 clotting factors are suppressed and thrombin is produced, an enzyme required to create fibrin threads that form a thrombotic clot. As a result, thrombus formation slows down.

Use of anticoagulants

Anticoagulants are indicated for:

Contraindications and side effects of anticoagulants

Anticoagulants are contraindicated for people suffering from the following diseases:

Bleeding hemorrhoids;
Peptic ulcer of the duodenum and stomach;
Kidney 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, or in 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 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. In some diseases, pathological ones appear in the blood. Physiological ones are normally found in plasma.

Physiological anticoagulants are divided into primary and secondary. The former are independently synthesized by the body and are constantly present in the blood. Secondary ones appear when coagulation factors are broken down during the formation and dissolution of fibrin.

Primary natural anticoagulants

Classification:

Antithrombins;
Antithromboplastins;
Inhibitors of fibrin self-assembly.

When the level of primary physiological anticoagulants in the blood decreases, the risk of thrombosis appears.

This group of substances includes the following list:

Secondary physiological anticoagulants

Formed during the process of blood clotting. They also appear when clotting factors are broken down and fibrin clots dissolve.

Secondary anticoagulants - what are they:

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

Pathological anticoagulants

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

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

Sometimes, during a number of autoimmune processes, pathological proteins that have an antithrombin or inhibitory effect can accumulate in the blood and paraproteinemia.

Mechanism of action of anticoagulants

These are drugs that affect blood clotting and are used to reduce the risk of blood clot formation.

Due to the formation of blockages in organs or blood vessels, the following may develop:

Gangrene of the limbs;
Ischemic stroke;
Thrombophlebitis;
Cardiac ischemia;
Inflammation of blood vessels;
Atherosclerosis.

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

"Direct"

They act directly on thrombin, reducing its activity. These drugs are prothrombin deactivators, thrombin inhibitors and inhibit thrombus formation. To prevent internal bleeding, it is necessary to monitor the parameters of the coagulation system.

Direct anticoagulants quickly enter the body, are absorbed into 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 hydrogen citrate;
Lepirudin, danaparoid.

Heparin

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

It is administered intravenously, intramuscularly and subcutaneously, and is also used as an ointment as a local remedy.

Heparins include:

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

Local antithrombotic drugs are not very effective and have low tissue permeability. Used to treat hemorrhoids, varicose veins, and bruises.

The following drugs are most often used with heparin:

Heparins for subcutaneous and intravenous administration are anti-clotting drugs that are individually selected and are not replaced by one another during the treatment process, since they are not equivalent in action.

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 threads and prevent platelet aggregation.

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

To prevent thrombosis and thromboembolism, Reviparin and Heparin are prescribed.

Sodium hydrogen citrate

This anticoagulant is used in laboratory practice. It is added to test tubes to prevent blood clotting. It is used for the preservation of blood and its components.

"Indirect"

They influence 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, drugs in this group have a relaxing effect on smooth muscles, stimulate 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 internally. The tablet form is used for a long time in an outpatient setting. Abrupt withdrawal leads to increased prothrombin and thrombosis.

These include:

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

“Indirect” drugs include:

Neodicoumarin;
Warfarin;
Acenocoumarol.

Warfarin (thrombin inhibitors) should not be taken in case of certain diseases of the liver and kidneys, thrombocytopenia, with a tendency to bleeding and acute bleeding, during pregnancy, with disseminated intravascular coagulation syndrome, 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. Itching, skin rash, vasculitis, eczema may occur.

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

New generation oral anticoagulants (NOACs)

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

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

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

New generation blood thinners have the following advantages:

The effect of the drug comes and goes quickly;
When taken, the risk of bleeding is reduced;
The drugs are indicated for patients who cannot take Warfarin;
Inhibition of thrombin-binding factor and thrombin is reversible;
The influence of food consumed, as well as other medications, is reduced.

However, new drugs also have disadvantages:

Must be taken regularly, whereas older medications can be skipped due to their long-lasting effects;
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.

New drugs Rivaroxaban, Apixaban and Dabigatran may be an alternative in case of atrial fibrillation. Their advantage is that there is no need to constantly donate blood during use, and they do not interact with other drugs.

However, NOACs are equally effective with no greater risk of bleeding.

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 vasodilator and antispasmodic effect.

The most famous antiplatelet agents:

Aspirin is the most common antiplatelet agent. An effective blood thinner, dilates blood vessels and prevents blood clots;
Tirofiban – interferes with platelet adhesion;
Eptifibatitis – inhibits platelet aggregation;
Dipyridamole is a vasodilator;
Ticlopidine - used for heart attacks, cardiac ischemia and for the prevention of thrombosis.

The new generation includes Brilint with the substance ticagrelor. It is a reversible antagonist of the P2Y receptor.

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 use can cause bleeding, including hidden bleeding. The prescription and calculation of dosage are carried out by the attending physician, who can take into account all 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 is that anticoagulants do not destroy the blood clot, but only slow down or prevent its development.

Pathological tachycardia requires medical or surgical treatment

Complications caused by vascular thrombosis are the main cause of death in cardiovascular diseases. Therefore, in modern cardiology, great importance is attached to preventing the development of thrombosis and embolism (blockage) of blood vessels. Blood coagulation in its simplest form can be represented as the interaction of two systems: platelets (cells responsible for the formation of a blood clot) and proteins dissolved in the blood plasma - coagulation factors, under the influence of which fibrin is formed. The resulting thrombus consists of a conglomerate of platelets entangled in fibrin threads.

To prevent the formation of blood clots, two groups of drugs are used: antiplatelet agents and anticoagulants. Antiplatelet agents prevent the formation of platelet clots. Anticoagulants block enzymatic reactions leading to the formation of fibrin.

In our article we will look at the main groups of anticoagulants, indications and contraindications for their use, and side effects.

Depending on the point of application, direct and indirect anticoagulants are distinguished. Direct anticoagulants inhibit thrombin synthesis and inhibit the formation of fibrin from fibrinogen in the blood. Indirect anticoagulants inhibit the formation of blood clotting factors in the liver.

Direct coagulants: heparin and its derivatives, direct thrombin inhibitors, as well as selective inhibitors of factor Xa (one of the blood clotting factors). Indirect anticoagulants include vitamin K antagonists.

Vitamin K antagonists

Indirect anticoagulants are the basis for the prevention of thrombotic complications. Their tablet forms can be taken for a long time on an outpatient basis. The use of indirect anticoagulants has been proven to reduce the incidence of thromboembolic complications (stroke) in the presence of an artificial heart valve.

Phenyline is not currently used due to the high risk of unwanted effects. Sinkumar has a long period of action and accumulates in the body, so it is used infrequently due to the difficulties of monitoring therapy. The most common vitamin K antagonist drug is warfarin.

Warfarin differs from other indirect anticoagulants in its early effect (10–12 hours after administration) and the rapid cessation of unwanted effects when the dose is reduced or the drug is discontinued.

The mechanism of action is associated with the antagonism of this drug and vitamin K. Vitamin K is involved in the synthesis of some blood clotting factors. Under the influence of warfarin, this process is disrupted.

Warfarin is prescribed to prevent the formation and growth of venous blood clots. It is used for long-term therapy in atrial fibrillation and in the presence of intracardiac thrombus. In these conditions, the risk of heart attacks and strokes associated with blockage of blood vessels by detached particles of blood clots is significantly increased. The use of warfarin helps prevent these serious complications. This drug is often used after a myocardial infarction to prevent a recurrent coronary accident.

After heart valve replacement, warfarin is required for at least several years after surgery. It is the only anticoagulant used to prevent the formation of blood clots on artificial heart valves. You need to take this medicine regularly for some thrombophilias, in particular antiphospholipid syndrome.