What medications are classified as anticoagulants? Anticoagulants - what they are and a list of drugs. The use of direct and indirect anticoagulants. What to do in case of overdose

24020 0

Thrombosis of vessels of various locations occupies one of the leading places among the causes of disability, mortality and reduction in the average life expectancy of the population, which determine the need for widespread use of drugs with anticoagulant properties in medical practice.

A special place in addressing the issues of thrombosis prevention belongs to oral anticoagulants. Indirect-acting anticoagulants (ANDA) are distinguished by the fact that they can be used for a long time (months, years) not only in hospitals of various profiles, but also in outpatient (home) conditions, the release form is in tablets and is many times cheaper than direct-acting anticoagulants that are administered injection.

Treatment with AEDs (vitamin K inhibitors) in the world is received by 1 in 200 patients, and in Russia - only 1 in 10,000. In recent years, there has been renewed interest in the therapeutic and prophylactic use of AEDs in patients with various pathological conditions of the cardiovascular system, neurological, oncological, orthopedic diseases, before and after surgery, with acquired and genetically determined thrombophilias. This interest has increased even more due to the appearance on the Russian market of one of the best drugs in this group - Wafarin. In Russia, 85% of patients in need of AED therapy take PHENYLIN, in Russia 90% of clinics control AED therapy, determining only the PROTHROMBIN INDEX!!! In Russia there are no standards for the duration of AED therapy.

All indirect anticoagulants are divided into three main groups: Monocoumarins - zarfarin (Coumadin), Marcumar (Falitrom, Liquomar, Phenprocoumon), Sincumar (acenocoumarin, Sintrom, Nikumarol); Dicoumarins - d and coumarin (bishydroxycoumarin, dicumarol), tromexane (pelentan, neodicoumarin); Indandiones - phenylin (phenindione, din-devan), dipaxin (diphenadione), omefin. Drugs of the third group have fallen out of use throughout the world due to the instability of their action, toxicity and a number of serious side effects.

Depending on the speed of onset of the hypocoagulation effect and the duration of the consequences of AED, they are divided into:

A - highly cumulative with a long period of action (syncumar, dicoumarin);

B - drugs with average cumulative properties (pelentan, neodicoumarin) and C - fast-acting (10-12 hours from the start of administration) with a short (about two days) effect. The latter includes warfarin - with an early hypocoagulative effect (compared to other coumarins), and rapid elimination of negative manifestations when the dose is reduced or completely discontinued.

The main mechanism of action of all AEDs is blockade of the final stage of synthesis (g-carboxylation) in liver cells of vitamin K-dependent blood coagulation factors (FVII, FX, FIX and FII - prothrombin) and two natural anticoagulants - protein C and its cofactor protein S (in lesser degree and non-progressive form) (Fig. 1).

Rice. 1.

The effect of vitamin K is manifested at the final stage of the synthesis of coagulation factors: FVII, FX, FIX and FII, as well as natural anticoagulants - protein C and its cofactor - protein S. The transition of inactive proenzymes to the active form occurs as a result of corbaxylation of glutamic acid residues on these vitamins. K-dependent proteins. When coagulation factors are activated, corbaxylated glutamic acid binds to calcium and, with its help, attaches to the phospholipids of cell membrane receptors (platelets, endothelial cells). During carboxylation, vitamin K is oxidized to an epoxide and then reduced to its active form by reductase. Warfarin inhibits vitamin K reductase and blocks the reduction of vitamin K epoxide to the active enzymatic form (Fig. 1) The degree of inhibition of vitamin K epoxide reductase depends on the concentration of warfarin in the liver, which in turn depends on the dose and pharmacokinetic characteristics of the drug in the patient.

The rate of decrease in the activity of all four coagulation factors under the influence of AED is not the same. The first to decrease is FVII, whose half-life in blood plasma is 2-4 hours, then FIX and FX, whose half-life is 48 hours, and the last is FII (prothrombin), approximately 4 days after the start of anticoagulants. Factor levels are restored in the same sequence after drug withdrawal: FVII quickly normalizes, later FIX and FX, and then prothrombin (after a few days).

Obviously, with this mechanism of action of AEDs, their anticoagulation effect does not appear immediately.

It has been proven that the effectiveness of the antithrombotic effect is due precisely to the decrease in the plasma concentration of FII - prothrombin. Therefore, when transferring a patient from direct-acting injection anticoagulants (unfractionated heparin or low-molecular-weight heparins) to maintenance therapy or thrombosis prevention, an AED should be prescribed 3-4 days before discontinuation of heparins, i.e. the patient should receive warfarin with heparin group drugs simultaneously for 2-3 days. If AEDs are prescribed after discontinuation of heparins, a period of time is created when the patient remains outside the influence of anticoagulants, and at the same time, an increase in the thrombotic process may occur - the “rebound” effect (the effect of drug withdrawal). Therefore, stopping heparins without first prescribing an AED 3-4 days before is a gross tactical mistake, fraught with serious complications - recurrent thrombosis. And, conversely, if it is necessary to transfer the patient from taking an AED to the administration of heparins, pentasaccharides (Arixtra) or other direct anticoagulants, it is necessary to cancel them earlier, and then after 2-3 days begin injections of direct anticoagulants.

In 1940, a group of American biochemists from Wisconsin under the leadership of K. Link isolated a toxic substance from ensiled sweet clover - dicumarol, which caused the death of a large number of cattle in the northern states of the USA and Canada in the 20s of the 20th century. dicumarol (3-3"-methyl-bis 4 hydroxycoumarin), causing a critical decrease in the level of coagulation factors of the prothrombin complex, was the cause of “sweet clover disease” - a fatal hemorrhagic blood diathesis. Dicumarol was originally used as a rat poison under the name WARFARIN(from the abbreviation of the company name - W isconsin A lumni Research F oudation, which created and sold it), and only since 1947 this drug began to be used in the treatment of myocardial infarction.

Warfarin was registered with the Pharmaceutical Committee of the Russian Federation at the end of 2001 and is currently quite widely represented on the domestic pharmacological market. Currently, warfarin has almost universally replaced all other AEDs, but its widespread introduction into clinical practice is not possible without organizing laboratory monitoring of its action for the correct selection of drug doses.

Warfarin, used in clinical practice, is presented as a levorotatory racemic compound (Fig. 1), which in the human body has greater activity than the dextrorotatory compound. The levorotatory isomer of warfarin is metabolized more quickly in the liver, and its metabolites - inactive or weakly active compounds - are excreted through the kidneys. Warfarin does not directly affect blood clots that have already formed. The goal of treatment with warfarin is to prevent the occurrence of blood clots and further increase in their size (generalization of the pathological coagulation process), as well as to prevent secondary thromboembolic complications, which result in consequences of varying severity or sudden death.

The use of an AED is indicated when long-term and continuous anticoagulant therapy or prophylaxis is necessary in the presence or threat of recurrent venous thrombosis of various locations, especially in cases of high ileofemoral thrombosis and pelvic vein thrombosis, which determine a high risk of pulmonary embolism. Continuous long-term use of AEDs is indicated for paroxysmal or persistent forms of atrial fibrillation, especially of atherosclerotic origin, and in cases of intra-atrial thrombus, which is a high risk factor for the development of cerebral strokes. Long-term use of an AED is indicated for heart valve replacement, when the likelihood of thromboembolic complications is very high, especially in the first few years after replacement. Lifelong antithrombotic therapy is indicated for a number of hereditary or acquired thrombophilias: antithrombin III deficiency, antiphospholipid syndrome.

Long-term use of AEDs is indicated in combination with cardio-selective beta blockers in the treatment of dilated and hypertrophic cardiopathy, since in parallel with the progression of heart failure there is a high risk of developing intracardiac thrombi and, as a consequence, ischemic strokes of various internal organs - systemic TE.

Similar prolonged (at least 3 months) use of AEDs is indicated following the use of heparins in orthopedic patients after plastic surgery of limb joints, in the treatment of bone fractures (especially the lower extremities) and immobilized patients for the purpose of preventing DVT and TE.

The main method of monitoring the hypocoagulative effect of an AED is the prothrombin test, which, according to WHO recommendations, is performed according to the method proposed back in 1937 by Kwiku. In recent decades, changes have been made to the methodology of this test and to the evaluation of its results, based on the determination of the prothrombin index (in %) using random samples of thromboplastin not standardized for sensitivity, which does not allow for correct dosing and monitoring of the therapeutic effects of AED. Unfortunately, this technique is widely used in many medical institutions of the Russian Federation and is a bad practice.

Currently, according to WHO recommendations, in world medical practice, control of the adequacy of AED use is carried out using the international normalized ratio (INR) of the prothrombin test, taking into account the “sensitivity index” (ISI) of the thromboplastin reagent. The use of standardized thromboplastin in the prothrombin test minimizes the variability of indications during repeated studies in assessing the hypocoagulative effect of AED (Fig. 2).

Rice. 2. Table for calculating MHO - international normalized ratio in comparison with the measured prothrombin index: IHR - international sensitivity index

Taking into account the sensitivity index of the thromboplastin used, MHO is determined using calculations:

Table 1 presents methods for calculating MHO depending on the value of MHI, recorded on thromboplastin produced by various companies.

Table 1. Examples of calculating MHO depending on the MIC value

Thrombo-plasteline	sick	PV control

An analysis of a number of large multicenter studies conducted in recent years has shown that the antithrombotic activity of warfarin is the same when maintaining MHO in the range of 2.0-3.0, and when this index increases to 3.5-4.5, the frequency and severity of hemorrhagic complications. These studies show that in cancer patients and elderly patients (> 75 years), the hypocoagulant effect of warfarin is already sufficient at MHO = 1.4-1.7.

All this led to a revision of previous recommendations to carry out more intensive anticoagulant therapy, the main disadvantage of which is the risk of hemorrhage and the fact that large doses of coumarins, at the initial stage of their use, cause a pronounced decrease in the blood level of the most important physiological anticoagulants - proteins C and S.

INR=24/11=2.21.2=2.6

The research results obtained allowed February 24, 2003. The US National Institutes of Health halted the large-scale, multicenter Prevention of Recurrent Venous Thromboembolism (PREVENT) Trial. An independent monitoring group found a high benefit of low-dose warfarin in the prevention of venous thromboembolism. The therapeutic dosage of warfarin was MHO - 1.5 to 2.0.

Clinically significant changes in the coagulation potential of the blood after taking the first dose of warfarin appear no earlier than after 8-12 hours, the maximum effect appears after 72-96 hours, and the duration of action of a single dose can range from 2 to 5 days.

Currently, the use of previously generally accepted starting loading doses (“increasing”) of warfarin is not recommended due to the real threat of a rapid decrease in the levels of natural anticoagulants (proteins C and S) compared to FII (protrambin), which can cause a “reverse” effect - thrombus formation . Warfarin therapy is recommended to begin with maintenance doses of 2.5-5 mg. Lower starting doses are indicated for patients over 60 years of age, natives of Asia, especially people of Chinese nationality, patients with impaired renal and hepatic function, arterial hypertension, as well as for concomitant therapy with drugs that enhance the anticoagulant effect of warfarin (allopurinol, amiodarone, ranitidine, simvastatin, anabolic steroids, omeprazole, streptokinase, sulfonamides, ticlopidine, thyroid hormones, quinidine).

An analysis of a number of large multicenter studies conducted in recent years has shown that the antithrombotic effectiveness of anticoagulants of the coumarin group is approximately the same when maintaining MHO in the range of 2.0-3.0 and above, but when MHO is >3.5, the frequency and severity of hemorrhagic complications is significantly increase (Fig. 3).

Rice. 3. Graph of the incidence of thromboembolic complications and bleeding depending on the level of MHO.

Currently, the accumulated experience of using warfarin in clinical practice allows us to recommend at the initial stage of treatment doses of warfarin not exceeding 5 mg per day, with further dose adjustment according to the dynamics of the MHO value, which in the vast majority of clinical situations should be maintained in the range of 2.0-3. 0, and in patients over 65 years of age - at levels from 1.4 to 2.0.

All hemorrhagic complications during anticoagulant therapy are divided into: minimum- microhematuria, the appearance of petechiae or bruises caused by rough clothing, a washcloth during hygienic washing, a cuff when measuring blood pressure; small- hematuria visible to the eye (pink urine or the color of “meat slop”), spontaneous nosebleeds, the presence of bruises; big- gastrointestinal bleeding, hemorrhages in the serous cavities (pleura, pericardium, peritoneum), retroperitoneal and intracranial hemorrhages, hematuria accompanied by the passage of blood clots and renal colic. According to extensive randomized and retrospective studies summarized in the materials of the American Consensus on Antithrombotic Therapy, with properly established laboratory monitoring of MHO for the anticoagulant effect of warfarin, the frequency of small hemorrhages does not exceed 1-2%, and large hemorrhages are up to 0.1% among all patients receiving warfarin. tk.n is contraindicated in the first third of pregnancy, coagulants of proteins C and denia (especially infectious-septicemia),

Table 2 shows an algorithm for adjusting the starting dose of warfarin at certain initial MHO values for each patient.

Table 2. Warfarin dose titration according to MHO data

		Warfarin doses (mg)
	Original MHO

AEDs have a number of contraindications for their use: severe liver damage, acute hepatitis and cirrhosis of the liver (of any etiology), recent hemorrhagic stroke (6 months before the start of treatment), and a history of recent gastrointestinal bleeding. Unlike heparins, AEDs should not be used in acute and subacute disseminated intravascular coagulation syndrome (severe CHF) of any origin (especially infectious-septic). This syndrome is characterized by a decrease in the concentration level in the blood plasma of natural anticoagulants proteins C and S (“consumption pathology”), the synthesis of which can be simultaneously blocked by indirect anticoagulants, which can aggravate the course of the first (thrombotic) phase of DIC syndrome, the clinical basis of which is a violation of microcirculation .

Warfarin is contraindicated in the first third of pregnancy, since it can contribute to the development of defects of the facial part of the skull (dip in the nose, flattening of the face, etc.) through blockade of enzymes involved in the formation of bone tissue in the fetus in the first trimester of pregnancy.

Currently, therapy for phlebothrombosis begins with 4-7 days of heparin administration. Warfarin is prescribed simultaneously with heparin 3-4 days before its discontinuation without the threat of dangerous hypocoagulation, starting with minimal therapeutic doses. Heparin is discontinued when the MHO level reaches 2.0-3.0.

The optimal duration of prophylactic therapy should effectively prevent recurrent thrombosis with minimal risk of bleeding. The frequency of sudden death due to recurrent deep vein thrombosis and recurrent pulmonary embolism, the probability of fatal bleeding, with correct AED therapy - MHO = 2.0-3.0 are significantly low and comparable. Patients with massive pulmonary embolism. respiratory failure, severe postthrombophlebitic syndrome require long-term anticoagulant therapy: from 3-6 months to a year. The Working Committee on the Use of AEDs of the International Society of Thrombosis and Hemostasis recommends mandatory 3-month AED prophylaxis for all patients who have suffered acute symptomatic thrombosis, maintaining an INR of 2.5.

The duration of prophylaxis increases to 6 months in cases of idiopathic thrombosis. Some patients with idiopathic thrombosis are recommended to conduct research for the presence of molecular genetically-dependent thrombophilias: Leideng mutation, prothrombin gene G20210A, antithrombin III deficiency, proteins C and S, and the presence of antiphospholipid antibodies. In cases of protein C and S deficiency, APS, and homozygous G20210A mutation, the duration of prophylaxis is increased to 2 years.

For primary prevention of CHD in patients with a very high risk of its development (metabolic syndrome, arterial hypertension, atherogenic dyslipopretinemia, type II diabetes mellitus, overweight, smoking, family history of CHD) in the presence of contraindications to aspirin, taking low doses of warfarin (MHO = 1 ,5) may be an alternative. In the absence of contraindications to aspirin, it is possible to combine its use in small doses (75-80 mg) with warfarin (MHO = 1.5). Isolated use of warfarin with an MHO level of 1.5 to 2.0 in patients with coronary artery disease reduces the risk of developing myocardial infarction and coronary death by 18%, when taking only aspirin (100 - 150 mg, taking into account undesirable effects) in a similar group of patients these indicators decrease by only 8%.

In a multicenter study, when prescribing heparins for 28 days followed by switching to warfarin in 999 patients with AMI, a 14% decrease in hospital mortality was noted compared with mortality in the group of patients not receiving warfarin. Warfarin, included in the AMI treatment program 27 days from the onset of the disease to the end of the 37-month follow-up, reduced overall mortality by 24%, the number of recurrent MI by 34% and ischemic strokes by 55%, while the incidence of hemorrhage was recorded at 0.6% in year.

In patients with atrial fibrillation, the incidence of which in people over 75 years of age reaches 14%, ischemic strokes develop in 23.5% of cases. Restoration of sinus rhythm in patients with atrial fibrillation (either drug or electropulse therapy) is accompanied by systemic TE in 1-3% of cases, which can develop several days and even weeks after successful cardioversion, which dictates the prophylactic use of warfarin. In these cases, it is recommended to prescribe warfarin (average MHO = 2.5) for 1 week before cardioversion and 4 weeks after it. Prophylactic use of warfarin in this group of patients reduces the risk of strokes and sudden death by 68 and 33%, respectively.

When treating patients with acute coronary syndrome or developed MI with direct anticoagulants, in 3-10% of cases the development of heparin-induced thrombocytopenia occurs - the platelet count decreases to a level of less than 100,000, accompanied by “ricochet” relapses of thrombosis. This syndrome requires immediate discontinuation of heparin, which dictates the need to prescribe warfarin to maintain anticoagulant therapy (in patients with ACS or MI) with an MHO of 1.5-2.0, but not higher.

Bleeding is the most significant and dangerous complication in the treatment of AED patients. The annual incidence of all bleeding during warfarin treatment ranges from 0.9 to 2.7%, fatal from 0.07 to 0.7%, hemorrhagic strokes account for 2% of all bleeding.

The first months of treatment are usually associated with a risk of bleeding (up to 3%) due to the instability of the level of coagulation when selecting the dose of warfarin. When assessing risk factors for bleeding, the following points should be considered:

age over 75 years;
a history of gastrointestinal bleeding;
arterial hypertension (diastolic blood pressure > 110 mmHg);
renal and liver failure;
cerebrovascular diseases;
malignant tumors;
alcoholism;
jointly taken anticoagulants and antiplatelet agents (aspirin 300 mg per day, low molecular weight heparins, platelet receptor inhibitors).

If bleeding occurs during warfarin therapy, it is necessary to assess the degree of its severity, urgently determine the MHO, and clarify the regimen for taking the drug and taking other medications.

At high MHO levels without bleeding (5.0-9.0), you should skip 1-2 doses of the drug, monitor MHO and resume therapy when therapeutic MHO values are reached. If there are “small” bleedings, vitamin K1 should be added to the above described tactics from 1.0 to 2.5 mg. If urgent correction of clinical manifestations of bleeding is necessary, the dose of vitamin K1 should be increased to 4 mg.

If there are clinical signs of “moderate” or “major” bleeding while taking warfarin, the drug should be completely discontinued, intravenous administration of vitamin K1 should be prescribed - 5.0-10 mg (repeated if necessary) with intravenous administration of concentrates of factors II, IX, X or fresh frozen plasma at the rate of 15 ml/kg.

Thus, indirect-acting anticoagulants are first-line drugs in the primary and secondary prevention of relapse or development of repeated MI, in the prolonged prevention and treatment of “venous thromboembolism” syndrome. Currently, in the group of drugs with an antagonistic effect on vitamin K (hypocoagulant effect), the leading place is occupied by warfarin with a rapid onset of action, relatively low accumulation and minimal side effects. Monitoring the therapeutic level of hypocoagulation must be carried out according to MHO data (optimal level = 2.0-3.0), which ensures comparability and adequate selection of the dose of the AED drug, to avoid complications in the form of bleeding of varying clinical severity.

Myocardial infarction. A.M. Shilov

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 fibrin formation, 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 clotting 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.

Various vascular diseases lead to the formation of blood clots. This leads to very dangerous consequences, since, for example, a heart attack or stroke can occur. To thin the blood, your doctor may prescribe medications that help reduce blood clotting. They are called anticoagulants and are used to prevent blood clots from forming in the body. They help block fibrin formation. Most often they are used in situations where blood clotting is increased in the body.

It can arise due to problems such as:

Varicose veins or phlebitis;
Thrombi of the inferior vena cava;
Blood clots of hemorrhoidal veins;
Stroke;
Myocardial infarction;
Arterial injuries in the presence of atherosclerosis;
Thromboembolism;
Shock, trauma or sepsis can also lead to blood clots.

Anticoagulants are used to improve blood clotting. If earlier they used Aspirin, now doctors have abandoned this technique, because there are much more effective drugs.

What are anticoagulants, pharmaceuticals. Effect

Anticoagulants- These are blood thinning drugs; in addition, they reduce the risk of other thromboses that may appear in the future. There are direct and indirect anticoagulants.

To quickly get rid of varicose veins, our readers recommend ZDOROV Gel. Varicose veins are the female “plague of the 21st century.” 57% of patients die within 10 years from blood clots and cancer! Life-threatening complications are: TROMBOPHLEBITIS (blood clots in the veins are present in 75-80% of varicose veins), TROPHIC ULCERS (tissue rotting) and of course ONCOLOGY! If you have varicose veins, you need to act urgently. In most cases, you can do without surgery and other severe interventions, on your own with the help of...

Direct and indirect anticoagulants

There are direct and indirect anticoagulants. The former quickly thin the blood and are eliminated from the body within a few hours. The latter accumulate gradually, providing a therapeutic effect in a prolonged form.

Since these drugs reduce blood clotting, you cannot lower or increase the dosage on your own, or shorten the time of administration. Medicines are used according to the regimen prescribed by the doctor.

Direct anticoagulants

Direct anticoagulants reduce thrombin synthesis. In addition, they inhibit the formation of fibrin. Anticoagulants are aimed at the liver and inhibit the formation of blood clotting.

Direct anticoagulants are well known to everyone. These are heparins for local action and for subcutaneous or intravenous administration. In another article you will find even more information about.

For example, local action:

These drugs are used for thrombosis of the veins of the lower extremities for the treatment and prevention of the disease.

They have a higher penetration rate, but are less effective than intravenous agents.

Heparins for administration:

Fraxiparine;
Clexane;
Fragmin;
Klivarin.

Typically, anticoagulants are selected to solve specific problems. For example, Klivarin and Troparin are used to prevent embolism and thrombosis. Clexane and Fragmin - for angina pectoris, heart attack, vein thrombosis and other problems.

Fragmin is used for hemodialysis. Anticoagulants are used when there is a risk of blood clots in any vessels, both arteries and veins. The activity of the drug lasts the whole day.

Indirect anticoagulants

Indirect anticoagulants are so named because they affect the creation of prothrombin in the liver, and do not directly affect coagulation itself. This process is long, but the effect is prolonged.

They are divided into 3 groups:

Monocoumarins. These include: Warfarin, Sinkumar, Gloomar;
Dicoumarins are Dicoumarin and Tromexane;
Indandiones are Phenilin, Omefin, Dipaxin.

Most often, doctors prescribe Warfarin. These drugs are prescribed in two cases: for atrial fibrillation and artificial heart valves.

Patients often ask what is the difference between Cardio Aspirin and Warfarin, and is it possible to replace one drug with another?

Experts answer that Aspirin Cardio is prescribed if the risk of stroke is not high.

Warfarin is much more effective than Aspirin, and it is better to take it for several months, or even throughout your life.

Aspirin corrodes the stomach lining and is more toxic to the liver.

Indirect anticoagulants reduce the production of substances that affect coagulation, they also reduce the production of prothrombin in the liver and are vitamin K antagonists.

Indirect anticoagulants include vitamin K antagonists:

Sinkumar;
Warfarex;
Fenilin.

Vitamin K is involved in the process of blood clotting, and under the influence of Warfarin its functions are impaired. It helps prevent blood clots from breaking off and blocking blood vessels. This drug is often prescribed after a myocardial infarction.

It is necessary to carefully consider taking this drug, as it has a lot of contraindications to food products that cannot be consumed simultaneously with this drug

There are direct and selective thrombin inhibitors:

Direct:

Angiox and Pradaxa;

Selective:

Eliquis and .

Any anticoagulants of direct and indirect action are prescribed only by a doctor, otherwise there is a high risk of bleeding. Indirect anticoagulants accumulate in the body gradually.

They are used only orally. It is impossible to stop treatment immediately; it is necessary to gradually reduce the dose of the drug. Abrupt withdrawal of the drug can cause thrombosis. An overdose of this group may cause bleeding.

Use of anticoagulants

Clinical use of anticoagulants is recommended for the following diseases:

Pulmonary and myocardial infarction;
Embolic and thrombotic stroke (except hemorrhagic);
Phlebothrombosis and thrombophlebitis;
Embolism of blood vessels of various internal organs.

Can be used as a preventive measure for:

Atherosclerosis of coronary arteries, cerebral vessels and peripheral arteries;
Heart defects: rheumatic mitral;
Phlebothrombosis;
Postoperative period to prevent blood clots.

Natural anticoagulants

Thanks to the process of blood clotting, the body itself ensures that the clot does not extend beyond the affected vessel. One milliliter of blood can help clot all fibrinogen in the body.

Due to its movement, blood maintains a liquid state, as well as due to natural coagulants. Natural coagulants are produced in tissues and then enter the bloodstream, where they prevent the activation of blood clotting.

These anticoagulants include:

Heparin;
Antithrombin III;
Alpha-2 macroglobulin.

Anticoagulant drugs - list

Direct-acting anticoagulants are absorbed quickly and their duration of action is no more than a day before repeated administration or application.

Anticoagulants
indirect effects accumulate in the blood, creating a cumulative effect.

They should not be canceled immediately, as this may promote thrombosis. When taking them, the dosage is gradually reduced.

Direct local anticoagulants:

Lyoton gel;
Hepatrombin;
Trombless

Anticoagulants for intravenous or intradermal administration:

Fraxiparine;
Clexane;
Fragmin;
Klivarin.

Indirect anticoagulants:

Hirugen;
Gyrulog;
Argatroban;
Warfarin Nycomed tablet;
Phenilin in tablet.

Contraindications

There are quite a few contraindications to the use of anticoagulants, so be sure to check with your doctor about the advisability of taking the drugs.

Cannot be used for:

Peptic ulcer;
Parenchymal diseases of the liver and kidneys;
Septic endocarditis;
Increased vascular permeability;
With high blood pressure due to myocardial infarction;
Oncological diseases;
Leukemia;
Acute cardiac aneurysm;
Allergic diseases;
Hemorrhagic diathesis;
Fibroids;
Pregnancy.

Use caution during menstruation in women. Not recommended for nursing mothers.

Side effects

An overdose of indirectly acting drugs may cause bleeding.

At
Taking Warfarin together with aspirin or other non-steroidal anti-inflammatory drugs (Simvastin, Heparin, etc.) increases the anticoagulative effect.